| 1. |
- Ramos-Casals, Manuel, et al.
(author)
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EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies.
- 2020
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 79:1, s. 3-18
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Journal article (peer-reviewed)abstract
- The therapeutic management of Sjögren syndrome (SjS) has not changed substantially in recent decades: treatment decisions remain challenging in clinical practice, without a specific therapeutic target beyond the relief of symptoms as the most important goal. In view of this scenario, the European League Against Rheumatism (EULAR) promoted and supported an international collaborative study (EULAR SS Task Force) aimed at developing the first EULAR evidence and consensus-based recommendations for the management of patients with SjS with topical and systemic medications. The aim was to develop a rational therapeutic approach to SjS patients useful for healthcare professionals, physicians undergoing specialist training, medical students, the pharmaceutical industry and drug regulatory organisations following the 2014 EULAR standardised operating procedures. The Task Force (TF) included specialists in rheumatology, internal medicine, oral health, ophthalmology, gynaecology, dermatology and epidemiology, statisticians, general practitioners, nurses and patient representatives from 30 countries of the 5 continents. Evidence was collected from studies including primary SjS patients fulfilling the 2002/2016 criteria; when no evidence was available, evidence from studies including associated SjS or patients fulfilling previous sets of criteria was considered and extrapolated. The TF endorsed the presentation of general principles for the management of patients with SjS as three overarching, general consensus-based recommendations and 12 specific recommendations that form a logical sequence, starting with the management of the central triplet of symptoms (dryness, fatigue and pain) followed by the management of systemic disease. The recommendations address the use of topical oral (saliva substitutes) and ocular (artificial tear drops, topical non-steroidal anti-inflammatory drugs, topical corticosteroids, topical CyA, serum tear drops) therapies, oral muscarinic agonists (pilocarpine, cevimeline), hydroxychloroquine, oral glucocorticoids, synthetic immunosuppressive agents (cyclophosphamide, azathioprine, methotrexate, leflunomide and mycophenolate), and biological therapies (rituximab, abatacept and belimumab). For each recommendation, levels of evidence (mostly modest) and TF agreement (mostly very high) are provided. The 2019 EULAR recommendations are based on the evidence collected in the last 16 years in the management of primary 2002 SjS patients and on discussions between a large and broadly international TF. The recommendations synthesise current thinking on SjS treatment in a set of overarching principles and recommendations. We hope that the current recommendations will be broadly applied in clinical practice and/or serve as a template for national societies to develop local recommendations.
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| 2. |
- Acar-Denizli, N., et al.
(author)
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Systemic phenotype related to primary Sjögren's syndrome in 279 patients carrying isolated anti-La/SSB antibodies
- 2020
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In: Clinical and Experimental Rheumatology. - : CLINICAL & EXPER RHEUMATOLOGY. - 0392-856X .- 1593-098X. ; 38:4; Suppl. 126, s. S85-S94
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Journal article (peer-reviewed)abstract
- Objective: To evaluate the systemic phenotype associated with the presence of isolated anti-La/SSB antibodies in a large international registry of patients with primary Sjogren's syndrome (pSS) fulfilling the 2002 classification criteria.Methods: The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014. Baseline clinical information from leading centres on clinical research in SS of the 5 continents was collected. Combination patterns of anti-Ro/SSA-La/SSB antibodies at the time of diagnosis defined the following four immunological phenotypes: double positive (combined Ro/SSA and La/SSB,) isolated anti-Ro/SSA, isolated anti-La/SSB, and immunonegative.Results: The cohort included 12,084 patients (11,293 females, mean 52.4 years) with recorded ESSDAI scores available. Among them, 279 (2.3%) had isolated anti-La/SSB antibodies. The mean total ESSDAI score at diagnosis of patients with pSS carrying isolated anti-La/SSB was 6.0, and 80.4% of patients had systemic activity (global ESSDAI score >= 1) at diagnosis. The domains with the highest frequency of active patients were the biological (42.8%), glandular (36.8%) and articular (31.2%) domains. Patients with isolated anti-La/ SSB showed a higher frequency of active patients in all ESSDAI domains but two (articular and peripheral nerve) in comparison with immune-negative patients, and even a higher absolute frequency in six clinical ESSDAI domains in comparison with patients with isolated anti-Ro/SSA. In addition, patients with isolated anti-La/SSB showed a higher frequency of active patients in two ESSDAI domains (pulmonary and glandular) with respect to the most active immunological subset (double-positive antibodies). Meanwhile, systemic activity detected in patients with isolated anti-La/SSB was overwhelmingly low. Even in ESSDAI domains where patients with isolated anti-La/SSB had the highest frequencies of systemic activity (lymphadenopathy and muscular), the percentage of patients with moderate or high activity was lower in comparison with the combined Ro/SSA and La/SSB group.Conclusion: Patients carrying isolated La/SSB antibodies represent a very small subset of patients with a systemic SS phenotype characterised by a significant frequency of active patients in most clinical ESSDAI domains but with a relative low frequency of the highest severe organ-specific involvements. Primary SS still remains the best clinical diagnosis for this subset of patients.
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| 3. |
- Asplund, Matthias, et al.
(author)
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Automatic laser scanning of wheel profiles: condition monitoring to achieve greater capacity for existing infrastructure in an extreme climate
- 2013
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In: Automatic laser scanning of wheel profiles. - India : Indian Railways, the host of 10th IHHA Conferance. - 9788192651910 ; , s. 445-451
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Conference paper (peer-reviewed)abstract
- The Iron Ore Line (Malmbanan) is a 473 km long track section located in northern Sweden and has been in operation since 1903. It is mainly used to transport iron ore and pellets from the mines in Kiruna and Malmberget to Narvik Harbour (Norway) in the northwest and Luleå Harbour (Sweden) in the southeast. The track section on the Swedish side is owned by the Swedish Government and managed by Trafikverket (the Swedish Transport Administration), while the ore wagons are owned and managed by the freight operator (LKAB). Due to the high axle load exerted by the iron ore transports, 30 tonnes, and the high demand for a constant ore/pellets flow, the track and wagons must be monitored and maintained on a regular basis. The condition of the wagon wheel profile is one of the most important aspects in this procedure. For this reason an automatic laser-based wheel profile monitoring system has been installed on this line. This system can automatically measure and monitor the wagon wheel profiles at speeds up to 130 km/h. The system was installed and is being operated in a collaboration project between the freight operator and infrastructure manager. The information generated is collected by the e-maintenance personnel at Luleå Railway Research Center (JVTC). The measurements will be used to diagnose the condition of the wheel and rail, and to optimize their maintenance further. This paper presents a study of the selection and the installation of the equipment. Some results from the measurements are shown. The system’s availability during performance in extreme climate conditions, with severe cold and large quantities of snow, is presented. Then the benefits and perceived challenges of the system are discussed. Some potential improvements in rail and wheel maintenance, to achieve more capacity, are analysed.
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| 4. |
- Asplund, Matthias, et al.
(author)
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Comparison of TOR lubrication systems on the iron ore line
- 2015
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Conference paper (peer-reviewed)abstract
- The Iron Ore Line (IOL) is a 473 km long track section which is located in northern Sweden and northern Norway, and has been in operation since 1903. The northern part is located above the Arctic Circle. The IOL is mainly used to transport iron ore and pellets from the mines in Kiruna and Malmberget to Narvik Harbour (Norway) in the northwest and Luleå Harbour (Sweden) in the southeast. The track section on the Swedish side is owned by the Swedish Government and managed by Trafikverket (the Swedish Transport Administration), while the ore wagons are owned and managed by the freight operator (LKAB).The IOL has seen a considerable increase in the axle load and traffic volume recently. Due to the introduction of new vehicles with a 30-ton axle load, the rails were gradually replaced between 2006 and 2009 with heavier rails, generally with a steel grade of 350LHT. The rail and wheels suffer from rolling contact fatigue (RCF) due to high friction between the rail and wheel. To control the wheel-rail interface, wayside top-of-rail (TOR) lubrication can be used. The reliability of the TOR lubrication equipment and the lubricants in northern conditions has not been investigated, and the long-term maintenance support required for TOR lubrication is unknown to the infrastructure manager. Furthermore, can TOR lubrication reduce the rail and wheel maintenance costs? This project has been conducted through collaboration between the main operator (LKAB) and the infrastructure manager (Trafikverket); the costs have been shared and the results analysed in collaboration. This paper describes the test period of two years, using two different TOR lubrication systems in two different places on the IOL, one situated in the northern loop and one in the southern loop, each with different operational conditions. The paper shows the actual operational conditions for the pilot test locations, the friction value close to the systems, the rail forces during the test period and some results for the noise measurements. Furthermore, the paper includes the improvements of system resulting from the test operation, and ends with recommendations for the continued use of TOR lubrication on the IOL.
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| 5. |
- Asplund, Matthias, et al.
(author)
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Improved wheel-rail system of Sweden’s iron ore line
- 2017
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In: Proceedings of the 11th International Heavy Haul Association Conference (IHHA 2017), Cape Town, South Africa, 2–6 September 2017. - 9780911382662 ; , s. 759-766
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Conference paper (other academic/artistic)abstract
- ABSTRACT: The Swedish Iron Ore Line (IOL) is the only heavy haul line in Europe. The northern part of the line is located above the Arctic Circle, a very harsh climate. Because of the introduction of new vehicles with a 30-tonnes axle load, the track were gradually replaced between 2006 and 2009 with heavier rails, mostly with a steel grade of R350LHT. Just after the first replacement of track in 2006, the project presented herein was established with the primary goal of improving the life length of the rail, and monitoring activities started. This project now has a unique database of rail degradation data. So far, the information has been used to improve the performance of the wheel-rail system and thus extend the life length of the rail, as well as to improve our knowledge of heavy haul operations in a cold climate. The paper discusses the project progress in general and gives some examples of improvements that have been successfully implemented, such as new rail profiles and a higher grinding frequency. Finally, it discusses the challenges of future capacity improvements, such as an increase in the axle load, and how these can be addressed.
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| 6. |
- Asplund, Matthias, et al.
(author)
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Reliability and measurement accuracy of a condition monitoring system in an extreme climate : a case study of automatic laser scanning of wheel profiles
- 2014
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In: Proceedings of the Institution of mechanical engineers. Part F, journal of rail and rapid transit. - : SAGE Publications. - 0954-4097 .- 2041-3017. ; 228:6, s. 695-704
-
Journal article (peer-reviewed)abstract
- The Iron Ore Line (Malmbanan) is a 473 km long track section located in northern Sweden and has been in operation since 1903. This track section stretches through two countries, namely Sweden and Norway, and the main part of the track runs on the Swedish side, where the owner is the Swedish Government and the infrastructure manager is Trafikverket (the Swedish Transport Administration). The ore trains are owned and managed by the freight operator and mining company LKAB. Due to the high axle load exerted by transportation of the iron ore, 30 tonnes, and the high demand for a constant flow of ore and pellets, the track and wagons must be monitored and maintained on a regular basis. The condition of the wagon wheel is one of the most important aspects in this connection, and here the wheel profile plays an important role. For this reason an automatic laser-based wheel profile monitoring system (WPMS) has been installed on this line using a system lifecycle approach that is based on the reliability, availability, maintainability and safety (RAMS) approach for railways. The system was prepared and installed and is being operated in a collaborative project between the freight operator and infrastructure manager. The measurements are used to diagnose the condition of the wheels, and to further optimize their maintenance. This paper presents a study of the concepts and ideas of the WPMS, and the selection, installation and validation of the equipment using a system lifecycle approach that is based on RAMS for railways. Results from the profile measurements and validation are shown. The system’s reliability during performance in extreme climate conditions, with severe cold and large quantities of snow, is presented. Then the benefits, perceived challenges and acquired knowledge of the system are discussed, and an improved V-model for the lifecycle approach is presented.
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| 7. |
- Asplund, Matthias, et al.
(author)
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Slutrapport avseende hjulprofilmätare i Sunderbyn
- 2014
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Reports (other academic/artistic)abstract
- Bakgrunden till projektets genomförande har varit den ökande mängden rälsbyten och mängden trafik med 30 tons axellast på Malmbanan. Spårunderhållet och hjulunderhållet har idag de överlägset högsta underhållskostnaderna av järnvägens olika system. Hjulprofilmätaren sågs som en möjlighet att kunna plocka ut de hjul som närmade sig underhållsgränserna för slitage, och därigenom kunna styra underhållet mer kostnadseffektivt.LKAB och Trafikverket enades därför att sätta upp ett gemensamt projekt där en ny typ av mätutrustning utprovades. För att få stöd med datalagring, bearbetning av data mm anlitades LTU och eMaintenanceLAB. Syftet med projektet har varit att undersöka och verifiera att en utrustning för automatisk hjulprofilmätning kan klara av att registrera och larma vid hjulpassager som avviker från de säkerhetsgränser och underhållsgränser som definieras i projektet med hänsyn till vårt klimat och våra förhållanden på Malmbanan. Den bärande idén i detta projekt har varit att man genom en kontinuerlig mätning av hjulprofiler ska kunna ta ut fordon ur trafik innan den avvikande hjulprofilen ger upphov till ett accelererande hjul- och rälslitage och därigenom sänka underhållskostnaden och öka livslängden på både hjul och räl. Projektet har även lett till en högre säkerhet på spåret då man kan mäta hjul som passerat säkerhetsgränsen för hjulparametrar och plockar bort dem, detta var inte var möjligt tidigare. De slutsatser som kan dras från detta projekt är följande:• Utvecklingsprojekt kan med fördel genomföras gemensamt mellan industri, infrastrukturförvaltare och akademi. • För att säkerställa ett bra resultat är det viktigt att genomföra alla steg i ett projekt från koncept till överlämnande. Som stöd för detta har V-modellen används som representerar livscykeln för systemet enligt EN-50126.• Val av tekniklösning och leverantör har gjorts utifrån tekniknivå, referensanläggningar samt drift- och supportmöjlighet och inte enbart utifrån pris. Ett utvecklingsprojekt likt detta handlar inte primärt om att få en utrustning i drift utan överföring av ”know how” kring vilka möjligheter och begränsningar det finns med denna teknik.• Resursbehovet för test och utvärdering underskattades och gjorde att projektet försenades ett år jämfört med ursprunglig tidplan. • Informationen som genereras från denna utrustning är mycket användbar för alla parter som arbetar med utveckling av underhåll inom järnvägen. • Utmaningen för att tillgodogöra sig nyttan från mätstationen ligger i att kunna förädla och integrera de genererade tillståndsdata till respektive underhållsorganisation.
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| 8. |
- Asplund, Matthias, et al.
(author)
-
The wheel profile measurement system at Sunderbyn, Sweden : final report
- 2014
-
Reports (other academic/artistic)abstract
- The background to the realisation of this project comprises an increasing number of rail replacements and an increasing volume of traffic with a 30-tonne axle load on the Swedish Iron Ore Line (IOL). When comparing the maintenance costs of all the different systems in the Swedish railway network, the maintenance costs for the track and wheels are by far the highest at present. The wheel profile measurement system (WPMS) was considered to provide the possibility of picking out wheels approaching the maintenance limits for wear and thereby of controlling maintenance in a more cost-effective way. Accordingly, LKAB and Trafikverket (the Swedish Transport Administration) reached an agreement concerning the initiation of a joint project in which a new type of measurement equipment would be tested. To obtain assistance with data storage and processing, etc., Luleå University of Technology (LTU) and its eMaintenance Lab were engaged in the project. The objective of the project has been to investigate and verify whether equipment for automatic wheel profile measurement is capable of registering wheel data and sending alerts concerning the passage of wheels which deviate from the safety and maintenance limits defined in the project, with regard to the climate and conditions prevailing along the Swedish IOL. The fundamental idea behind this project has been that, through continuous measurement of wheel profiles, one should be able to take vehicles out of service before any deviating wheel profiles give rise to accelerating wheel and rail wear, and that one should thereby be able to reduce the maintenance costs and increase the operational life of both wheels and rails. An additional result of the project has been increased safety on the track, since it is possible to measure wheels that have exceeded the safety limit for wheel parameters and remove them, which was impossible previously. The following conclusions can be drawn from this project.• There are benefits to be derived from development projects conducted jointly between industry, infrastructure managers and academia. • In order to ensure good results, it is important to perform all the steps in a project, from the concept phase to the handing-over phase. In support of this, the V-model was used, which represents the life cycle of the system according to EN 50126. • The selection of a technical solution and a supplier was made on the basis of the technology level, reference installations, and operation and support possibilities, and not merely based on the price. A development project of this nature is not primarily a question of putting equipment into operation, but of transferring knowhow concerning the possibilities and limitations associated with the technology in question. • The resource requirement for testing and evaluation was underestimated, which resulted in the project being delayed by one year compared with the original timetable. • The information generated by the equipment installed is very useful for all parties working with the development of railway maintenance. • The challenge with regard to utilising the benefits afforded by the measurement station at Sunderby lies in the ability to process the generated condition data for the maintenance organisations concerned and integrate these data in the operations of these organisations.
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| 9. |
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| 10. |
- Brito-Zeron, P., et al.
(author)
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How immunological profile drives clinical phenotype of primary Sjögren's syndrome at diagnosis : analysis of 10,500 patients (Sjögren Big Data Project)
- 2018
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In: Clinical and Experimental Rheumatology. - : CLINICAL & EXPER RHEUMATOLOGY. - 0392-856X .- 1593-098X. ; 36:3, s. S102-S112
-
Journal article (peer-reviewed)abstract
- Objective: To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjogren's syndrome (SjS).Methods: The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonised data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfillment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays.Results: By January 2018, the participant centres had included 10,500 valid patients from 22 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti-La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementaemia and especially cryoglobulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for ctyoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESSDAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains).Conclusion: We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalised management during the follow-up of patients with primary SjS.
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| 11. |
- Brito-Zerón, Pilar, et al.
(author)
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Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's syndrome at diagnosis in 8310 patients : a cross-sectional study from the Big Data Sjögren Project Consortium
- 2017
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:6, s. 1042-1050
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis.METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed.RESULTS: We included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69).CONCLUSIONS: This study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis.
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| 12. |
- Ekberg, Anders, 1967, et al.
(author)
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Identifying the root causes of damage on the wheels of heavy haul locomotives and its mitigation
- 2014
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In: Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit. - : SAGE Publications. - 0954-4097 .- 2041-3017. ; 228:6, s. 663-672
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Journal article (peer-reviewed)abstract
- The paper illustrates how damage patterns in the form of rolling contact fatigue (RCF) on wheels, can be employed to identify and improve underlying operational conditions. The focus is on RCF of locomotive wheels operating on the Iron Ore Line in northern Sweden and Norway. Seasonal changes and damage patterns are charted. Potential root causes for observed damage patterns are identified and investigated. Mitigating actions are proposed and the efficiency of implemented actions is quantified.
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| 13. |
- Ekberg, Anders, 1967, et al.
(author)
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Identifying the root causes of damage on the wheels of heavy haul wheel damage phenomena
- 2013
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In: Proceedings of the 10th International Heavy Haul Conference (IHHA 2013), February 4–6, New Dehli, India. ; , s. 520-526
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Conference paper (peer-reviewed)abstract
- The paper illustrates how damage patterns, in particular in the form of rolling contact fatigue (RCF), can be employed to identify underlying operational conditions. In particular the focus is on RCF of wheel occurring at the Iron Ore line in north Sweden and Norway. The paper charts seasonal changes and damage patterns, and potential root causes are identified and investigated. Finally mitigating actions are proposed.
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| 14. |
- Fröhling, Robert, et al.
(author)
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Guest editorial of Special Issue on High Tech in Heavy Haul
- 2009
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In: Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit. - : SAGE Publications. - 0954-4097 .- 2041-3017. ; 223, s. i-ii
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Journal article (peer-reviewed)
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| 15. |
- Hernandez-Molina, Gabriela, et al.
(author)
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Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies
- 2022
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In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:1, s. 243-255
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Journal article (peer-reviewed)abstract
- ObjectiveTo characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes.MethodsBy January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified.ResultsThere were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL).ConclusionIn the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.
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| 16. |
- Hossein Nia, Saeed, 1983-, et al.
(author)
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Can Simulation Help to Find the Sources of Wheel Damages? : Investigation of Rolling Contact fatigue on the Wheels of a Three-Piece Bogie on the Swedish Iron ore Line via Multibody Simulation Considering Extreme Winter Condition
- 2013
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In: Proceedings of the 10Th International Heavy Haul Association Conference IHHA. ; , s. 357-363
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Conference paper (peer-reviewed)abstract
- The Swedish iron ore company LKAB uses freight wagon with three-piece bogie to transport iron ore from the mines in Kiruna and Malmberget to Luleå and Narvik. A simulation model of the freight wagon has been built at KTH Rail Vehicles using the Multibody simulation code GENSYS. The purpose is to investigate possible sources of rolling contact fatigue (RCF) of the wheels given the high level of damage, particularly in the winter.The wooden sleeper track has recently been replaced by a stiffer track with concrete sleeper. After the change, the frequency of RCF increased. Therefore, both track models are implemented. A parameter study is performed on vertical track stiffness and viscous damping regarding the seasonal variations of the track conditions. Another parameter study is carried out on the influence of the wheel-rail friction coefficient because in winter time the climate is very dry along most parst of the Swedish iron-ore line. The impact of new and worn wheel profiles on RCF is investigated. The wear number is calculated and compared with the RCF probability.The shakedown map is used to study the influence of an increase in track forces on RCF. It is shown that RCF happens on the tread of the inner wheels while negotiating curves below approximately 450 m radius. And in cold dry climate conditions when the wheel-rail friction coefficient significantly increases and when the wheel material behaves more brittle, the risk of RCF is significantly increased while the wear rate is not high enough to wear out the initiated cracks. It is proven that using concrete sleepers and vertically stiffer track might increase the track forces but it cannot be the main reason for severe RCF during winter.
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| 17. |
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| 18. |
- Joborn, Martin, 1967-, et al.
(author)
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Energy efficiency and on-time performance for heavy haul trains
- 2011
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In: International Heavy Haul Association Conference, Conference Proceedings.
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Conference paper (peer-reviewed)abstract
- The driving advisory system CATO has been installed at iron ore trains at LKAB, Sweden. CATO uses radio communication to communicate, e.g., the operational timetable and train status between the train control center and the trains. The advisories both enable the drivers to keep the operational timetable with very high precision and reduce the energy consumption by 20-25 percent. CATO’s speed advisories are easy to follow, and can easily be adapted to be relevant for heavy haul driving under extreme conditions.
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| 19. |
- Khatri, B., et al.
(author)
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Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
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| 20. |
- Landegren, Nils, et al.
(author)
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Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis
- 2016
-
In: Journal of the American Society of Nephrology: JASN. - 1533-3450 .- 1046-6673. ; 27:10, s. 3220-3228
-
Journal article (peer-reviewed)abstract
- Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct-specific water channel aquaporin 2, whereas autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells.
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| 21. |
- Larsson-Kråik, Per-Olof, et al.
(author)
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Managing rail degradation on the Malmbanan
- 2007
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In: Railway Gazette International. - 0373-5346. ; 163:6
-
Journal article (other academic/artistic)abstract
- An upgrading programme started in 1998 and due to be completed by 2010 is allowing the introduction of heavier axleloads on Sweden's heavy haul iron ore line, permitting gross train weights to be increased to more than 8 000 tonnes. But the transition requires careful management if degradation of the infrastructure is to be kept under control
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| 22. |
- Leffler, Ann-Sofie, et al.
(author)
-
Somatosensory perception and function of diffuse noxious inhibitory controls (DNIC) in patients suffering from rheumatoid arthritis.
- 2002
-
In: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 6:2, s. 161-76
-
Journal article (peer-reviewed)abstract
- The purpose was to investigate the influence of ongoing pain from an inflammatory nociceptive pain with two different disease durations on somatosensory functions and the effect of heterotopic noxious conditioning stimulation (HNCS) on 'diffuse noxious inhibitory controls' (DNIC) related mechanisms. Eleven patients with rheumatoid arthritis of a short duration (<1 year) (RA1), and 10 patients with rheumatoid arthritis of longer duration (>5 years) (RA5) as well as 21 age- and sex-matched healthy controls participated. Pressure pain sensitivity, low threshold mechanoreceptive function and thermal sensitivity, including thermal pain, were assessed over a painful and inflamed joint as well as in a pain-free area, i.e. the right thigh before HNCS (cold-pressor test) and repeated at the thigh only during and following HNCS. In RA1 and RA5 allodynia to pressure was seen over the joint (p<0.02 and p<0.001 respectively) in conjunction with hypoaesthesia to light touch (p<0.02) and hyperaesthesia to innocuous cold (p<0.05) in RA5. At the thigh, allodynia to pressure was found in RA5 (p<0.002). During HNCS, the sensitivity to pressure pain decreased in patients and controls alike (p<0.001). In conclusion, over an inflamed joint allodynia to pressure was found in both RA groups, with additional sensory abnormalities in RA5. In a non-painful area, allodynia to pressure was found in RA5, suggesting altered central processing of somatosensory functions in RA5 patients. The response to HNCS was similar in both RA groups and controls, indicating preserved function of DNIC-related mechanisms.
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| 23. |
- Lin, Janet, et al.
(author)
-
Data analysis of heavy haul wagon axle loads on Malmbanan line, Sweden : A case study for LKAB
- 2016
-
Reports (other academic/artistic)abstract
- The research presented in this report was carried out by Operation and Maintenance Engineering at Luleå University of Technology (LTU) from November 2015 to April 2016. LKAB initiated the research study and provided financial support. The purpose of this research was to support LKAB and Trafikverket in their operational strategy review and optimization of future axle load implementations. It developed five research questions and answered them by analyzing the data for the Malmbanan iron ore train axle loads for 2015.Data analysis comprises four parts. In the first part (section 2), the analysis focuses on axle loads of all loaded trains operating at three different terminals: Kiruna, Malmberget, and Svappavaara. In addition, it examines the differences of three weighing locations in Kiruna, five weighing locations in Malmberget and four weighing locations in Svappavaara (12 weighing locations). Based on these results, the analysis in the second part (section 3) focuses on the heavy haul wagon. Wagon loads are evaluated and predicted for different loading rules (31.0 and 32.5 tons separately). To optimize the current loading rules, the third part of the analysis (section 4) proposes a novel approach to optimize the wagon axle loads: “three sigma prediction”. Under this approach, Kiruna, Malmberget and Svappavaara can set new target loads based on various risk levels. In the fourth and final part of the data analysis (section 5), a comparison study is carried out by collecting axle load data for the test train (with a 32.5 ton axle load) using three different measurement systems in Malmberget, Sävast and Sunderbyn. Finally, sections 6 and 7 summarize the results and make some recommendations for future work. The work presented in this report should give LKAB and Trafikverket a good overview of the load distribution for the ore trains operating on Malmbanan line. It can serve as input into the process of evaluating possible changes in axle load limits. It also gives LKAB a base from which to identify and work with optimization of the various loading places to load trains more efficiently and save costs.
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| 24. |
- Lin, Jing, et al.
(author)
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Data analysis of wheel-sets' running surface wear based on re-profiling measurement : a case study at Malmbanan
- 2015
-
In: IHHA 2015 Conference proceedings. - : International Heavy Haul Association. - 9780646940069 ; , s. 924-930
-
Conference paper (peer-reviewed)abstract
- In this paper, the wheel-sets’ running surface wear data based on re-profiling measurement from 16 bogies of heavy haul locomotives at Malmbanan (Sweden) are studied. The case study undertakes: reliability and degradation analysis, wear rate analysis and their comparison (including total wear rate, natural wear rate, re-profiling wear rate, the ratio of re-profiling and natural wear). The results show that: 1) for the studied group, a linear degradation path is more suitable; 2) following the linear degradation, the best life distribution is a 3-parameter Weibull distribution; 3) comparing the wearing data of the wheel-sets’ running surfaces is an effective way to optimize maintenance strategies; 4) more natural wear occurs for the wheels installed in axle 1 and axle 3, supportive evidence for other related studies at Malmbanan.
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| 25. |
- Lundtoft, Christian, et al.
(author)
-
Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases
- 2022
-
In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 74:8, s. 1440-1450
-
Journal article (peer-reviewed)abstract
- Objective Copy number variation of the C4 complement components, C4A and C4B, has been associated with systemic inflammatory autoimmune diseases. This study was undertaken to investigate whether C4 copy number variation is connected to the autoimmune repertoire in systemic lupus erythematosus (SLE), primary Sjogrens syndrome (SS), or myositis. Methods Using targeted DNA sequencing, we determined the copy number and genetic variants of C4 in 2,290 well-characterized Scandinavian patients with SLE, primary SS, or myositis and 1,251 healthy controls. Results A prominent relationship was observed between C4A copy number and the presence of SSA/SSB autoantibodies, which was shared between the 3 diseases. The strongest association was detected in patients with autoantibodies against both SSA and SSB and 0 C4A copies when compared to healthy controls (odds ratio [OR] 18.0 [95% confidence interval (95% CI) 10.2-33.3]), whereas a weaker association was seen in patients without SSA/SSB autoantibodies (OR 3.1 [95% CI 1.7-5.5]). The copy number of C4 correlated positively with C4 plasma levels. Further, a common loss-of-function variant in C4A leading to reduced plasma C4 was more prevalent in SLE patients with a low copy number of C4A. Functionally, we showed that absence of C4A reduced the individuals capacity to deposit C4b on immune complexes. Conclusion We show that a low C4A copy number is more strongly associated with the autoantibody repertoire than with the clinically defined disease entities. These findings may have implications for understanding the etiopathogenetic mechanisms of systemic inflammatory autoimmune diseases and for patient stratification when taking the genetic profile into account.
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| 26. |
- Mofors, Johannes, et al.
(author)
-
Cigarette smoking patterns preceding primary Sjögren's syndrome
- 2020
-
In: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 6:3
-
Journal article (peer-reviewed)abstract
- Background: Cigarette smoking is a well-established risk factor for several autoimmune diseases, but its role in primary Sjogren's syndrome (pSS) remains unclear. Here, we investigated the association between cigarette smoking and subsequent development of pSS.Methods: Information on smoking habits was collected from lifestyle habit questionnaires of patients with pSS (n=815) and a matched control group (n=4425) for a case-control study. Differences in smoking exposure were analysed by conditional logistic regression. Potential interactions between smoking and risk-associated human leucocyte antigens (HLA) were assessed by multivariate regression.Results: The fraction of patients with pSS having ever smoked prior to diagnosis was lower than in controls (OR 0.67, 95% CI 0.55 to 0.81). Current smoking at diagnosis was also less prevalent in cases (OR 0.37, 95% CI 0.26 to 0.53). However, period prevalence of smoking during early adulthood was not statistically different from controls (OR 0.89, 95% CI 0.66 to 1.22) but markedly decreased over time. This was partly due to patients being more prone to stop smoking, starting already 30 years prior to diagnosis (OR 2.01, 95% CI 1.22 to 3.30). Smoking patterns were also stratified by autoantibody status, yielding similar estimates. No interaction effects between HLA-DRB1 haplotypes and smoking were observed.Conclusion: The observed smoking patterns indicate that individuals who develop pSS smoke equally much as the general population during early life but are then more prone to stop. The data can be interpreted as smoking conferring protective effects, or reflecting early symptoms of pSS that affect smoking habits, emphasising the slow, progressive development of the disease.
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| 27. |
- Mofors, J., et al.
(author)
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Concomitant Ro/SSA and La/SSB antibodies are biomarkers for the risk of venous thromboembolism and cerebral infarction in primary Sjögren's syndrome
- 2019
-
In: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 286:4, s. 458-468
-
Journal article (peer-reviewed)abstract
- Background: To assess the risk of incident cardiovascular disease in patients with primary Sjögren's syndrome, overall and stratified by Ro/SSA and La/SSB autoantibody status.Methods: A cohort of patients with primary Sjögren's syndrome in Sweden (n = 960) and matched controls from the general population (n = 9035) were included, and data extracted from the National Patient Register to identify events of myocardial infarction, cerebral infarction and venous thromboembolism. Hazard ratios were estimated using cox proportional hazard regressions.Results: During a median follow‐up of 9.5 years, the overall hazard ratio (HR) was 1.6 (95% CI 1.2–2.1) for myocardial infarction, 1.2 (95% CI 0.9–1.7) for cerebral infarction and 2.1 (95% CI 1.6–2.9) for venous thromboembolism. Patients positive for both Ro/SSA and La/SSB autoantibodies had a substantially higher risk of cerebral infarction (HR 1.7, 95% CI 1.0–2.9) and venous thromboembolism (HR 3.1, 95% CI 1.9–4.8) than the general population. These risks were not significantly increased in Ro/SSA‐ and La/SSB‐negative patients. Among autoantibody‐positive patients, the highest HR of cerebral infarction was seen after ≥10 years disease duration (HR 2.8, 95% CI 1.4–5.4), while the HR for venous thromboembolism was highest 0–5 years after disease diagnosis (HR 4.7, 95% CI 2.3–9.3) and remained high throughout disease duration.Conclusions: Primary Sjögren's syndrome is associated with a markedly increased risk of cardiovascular disease and the presence of Ro/SSA and La/SSB autoantibodies identify the subgroup of patients carrying the highest risk. These findings suggest that monitoring and prevention of cardiovascular disease in this patient group should be considered.
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| 28. |
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| 29. |
- Mofors, J., et al.
(author)
-
Infections increase the risk of developing Sjögren's syndrome
- 2019
-
In: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 285:6, s. 670-680
-
Journal article (peer-reviewed)abstract
- Objective: Environmental factors have been suggested in the pathogenesis of rheumatic diseases. We here investigated whether infections increase the risk of developing primary Sjögren's syndrome (pSS).Methods: Patients with pSS in Sweden (n = 945) and matched controls from the general population (n = 9048) were included, and data extracted from the National Patient Register to identify infections occurring before pSS diagnosis during a mean observational time of 16.0 years. Data were analysed using conditional logistic regression models. Sensitivity analyses were performed by varying exposure definition and adjusting for previous health care consumption.Results: A history of infection associated with an increased risk of pSS (OR 1.9, 95% CI 1.6–2.3). Infections were more prominently associated with the development of SSA/SSB autoantibody‐positive pSS (OR 2.7, 95% CI 2.0–3.5). When stratifying the analysis by organ system infected, respiratory infections increased the risk of developing pSS, both in patients with (OR 2.9, 95% CI 1.8–4.7) and without autoantibodies (OR 2.1, 95% CI 1.1–3.8), whilst skin and urogenital infections only significantly associated with the development of autoantibody‐positive pSS (OR 3.2, 95% CI 1.8–5.5 and OR 2.7, 95% CI 1.7–4.2). Furthermore, a dose–response relationship was observed for infections and a risk to develop pSS with Ro/SSA and La/SSB antibodies. Gastrointestinal infections were not significantly associated with a risk of pSS.Conclusions: Infections increase the risk of developing pSS, most prominently SSA/SSB autoantibody‐positive disease, suggesting that microbial triggers of immunity may partake in the pathogenetic process of pSS.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Nordmark, Thomas
(author)
-
A Mining Companies Development of a Green Power Concept for Rebuilding Diesel Locomotives
- 2015
-
In: 11th International Heavy Haul Conference, (IHHA 2015). - : International Heavy Haul Association. - 9780646940069 ; , s. 449-458
-
Conference paper (peer-reviewed)abstract
- LKAB mining company needed to upgrade four T46 terminal locomotives because they had reached their technical life length and lacked the tractive effort to handle the new longer and heavier trains. The first idea was to buy new locomotives, but none suited LKAB’s specific requirements. The next idea was to turn to a locomotive rebuilding company. Unfortunately, the company closed down, forcing LKAB to do the rebuilding. This paper describes how the mining company turned locomotives built in 1973 into modern environmentally friendly, state-of-the art locomotives, tailor-made for the specific requirements and conditions of LKAB in operating iron ore transports in Kiruna Sweden. LKAB was the first company in Europe to meet the European emission regulation 3A/EPA (US Tier 2) by installing a diesel engine in a loco and therefor the name of the loco was T46 Green Power Concept (GPC). The most important result was the discovery that a mining company, or any other company, can rebuild a locomotive to meet the company’s specific requirements and tailor it to its operation, if it is important to do so, provided skilled people are available for this task. The money spent was equal to the cost of purchasing new locomotives, and delivery time was equal to having the rebuilding subcontracted out.
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| 34. |
- Nordmark, Thomas, et al.
(author)
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Use of electro-dynamic braking on locomotives and its effect on rolling contact fatigue
- 2017
-
In: Proceedings of the 11th International Heavy Haul Association Conference (IHHA 2017), Cape Town, South Africa, 2–6 September 2017. - 9780911382662 ; , s. 1133-1137
-
Conference paper (peer-reviewed)abstract
- ABSTRACT: The mining company LKAB uses IORE locomotives to haul iron ore trains. When evaluated using life cycle cost (LCC) analysis for reliability, availability, maintainability, and safety (RAMS), wheel life is found to be 930,000 km. The IORE locomotives are equipped with electro-dynamic (ED) brakes, but because of the inability of the contact grid to handle the full regenerative energy from the locomotives, the use of theED-brake was restricted until the contact grid was upgraded in 2010. From around 2011, the wheel life started to decrease because of increased rolling contact fatigue (RCF), dropping to around 350,000 km. LKABsuspected the use of the ED-brake was contributing to the RCF problem. A field test compared one locomotive with ED-braking reduced to a minimum level to a locomotive with full ED-braking capacity. The wheels of the two locomotives were visually inspected at intervals of about 13,000 km. The results showed no difference in RCF performance between the locomotives.
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| 35. |
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| 36. |
- Palo, Mikael, et al.
(author)
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Condition monitoring at the wheel/rail interface for decision-making support
- 2014
-
In: Proceedings of the Institution of mechanical engineers. Part F, journal of rail and rapid transit. - : SAGE Publications. - 0954-4097 .- 2041-3017. ; 228:6, s. 705-715
-
Journal article (peer-reviewed)abstract
- Many railway assets, such as wheels, suffer from increasing deterioration during operation. Good condition monitoring based on good decision-making techniques can lead to accurate assessment of the current health of the wheels. This, in turn, will improve safety, facilitate maintenance planning and scheduling, and reduce maintenance costs and down-time. In this paper, wheel/rail forces are selected as a parameter (feature) for the condition monitoring of wheel health. Once wheels are properly thresholded, determining their condition can help operators to define maintenance limits for their rolling stock. In addition, if rail forces are used as condition indicators of wheel wear, it is possible to use measurement stations that cost less than ordinary profile stations. These stations are located on ordinary tracks and can provide the condition of wheelsets without causing shutdowns or slowdowns of the railway system and without interfering with railway traffic. The paper uses the iron-ore transport line in northern Sweden as a test scenario to validate the use of wheel/rail forces as indicators of wagon and wheel health. The iron-ore transport line has several monitoring systems, but in this paper only two of these systems will be used. Wheel/rail force measurements are performed on curves to see how the vehicle negotiates the curve, and wheel profile measurements are done on tangent track not far away. The vehicles investigated are iron-ore wagons with an axle load of 30 tonnes and a loaded top speed of 60 km/h. The measurements are non-intrusive, since trains are moving and assets are not damaged during the testing process
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| 37. |
- Palo, Mikael, et al.
(author)
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Wheel/rail condition monitoring to support rolling stock maintenance actions
- 2013
-
In: Proceedings of 10th International Heavy Haul Association Conference.
-
Conference paper (peer-reviewed)abstract
- Wheel/rail guidance is made possible by the shapes of wheel and rail profiles. For train operators to increase revenue and decrease cost for railway infrastructure owners they must monitor the conditions of the assets.The Iron Ore Line in northern Sweden has two different monitoring systems installed to monitor con- ditions of all passing vehicles. The wheel/rail force measurement are made in a curve to see the how the vehicle negotiate the curve, and the wheel profile measurements are done on tangent track not far away. The vehicles investigated are iron ore wagons from LKAB mining company with an axle load of 30 tonnes and a loaded top speed of 60 km/h.This study uses the condition from either wheel wear or wheel/rail forces as decision-making support for maintenance actions. A correlation between forces and wheel wear will make it possible to use this kind of force measurement stations at more places than just profile stations. This correlation will help to obtain maintenance limits for the operators to use on their rolling stock.
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| 38. |
- Ramirez, Jorge, et al.
(author)
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Difference in Clinical Presentation between Female and Male Patients with Primary Sjogren's Syndrome at Diagnosis and in Long-Term Follow-up
- 2017
-
In: Arthritis & Rheumatology. - : Wiley-Blackwell. - 2326-5191 .- 2326-5205. ; 69
-
Journal article (other academic/artistic)abstract
- Background/Purpose: Despite men being less prone to develop autoimmune diseases, male sex has been associated with a more severe disease course in several systemic autoimmune diseases. In the present study, we aimed to identify differences in clinical presentation between the sexes at the time of diagnosis and during long-term follow-up of primary Sjögren's syndrome (pSS), and to establish whether male sex is associated with a more severe form of pSS. Methods: Incident, treatment naïve patients (n=199, 186 females and 13 males) from Stockholm, Sweden were prospectively included during a 5-year period and examined for items of classification criteria for pSS as well as extraglandular manifestations (EGM). Serum was sampled at the time of diagnosis and anti-Ro52/SSA levels measured by ELISA. Replication of significant findings was confirmed in an independent cohort of incident pSS patients from Pisa, Italy (n=377, 368 females and 9 males), and meta-analysis performed. We further studied a cohort of 967 patients with prevalent pSS (899 females and 68 males) from Scandinavian clinical centers. The mean follow-up time (years) was 8.8 ± 7.6 for women and 8.5 ± 6.2 for men (ns). Clinical data including serological and hematological parameters, glandular, EGM and comorbidities were compared between men and women. Results: An increased frequency of EGM in men at diagnosis was observed and replicated (p=0.05, p=0.0003, and pmeta=0.002, respectively). This related to pulmonary involvement, vasculitis and lymphadenopathy being more common in men, for whom a lower age at diagnosis was observed in the exploratory cohort. Additionally, SSA positive male patients had significantly higher levels of anti-Ro52 levels than their female counterparts (p=0.02). After long-term follow-up, male patient serology was characterized by more frequent positivity for anti-SSA and anti-SSB (p=0.02), and ANA (p=0.02). Also, men with pSS were more frequently diagnosed with interstitial lung disease (p=0.008), lymphadenopathy (p=0.04) and lymphoma (p=0.007). Conversely, concomitant hypothyroidism was more common among female patients (p=0.009). Conclusion: Our analysis of two independent cohorts of incident pSS and a large cohort of prevalent pSS demonstrates significant differences between women and men with pSS. Notably, men present with more EGM, enhanced serological profile and a higher frequency of lymphoma development.
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| 39. |
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| 40. |
- Ramos-Casals, Manuel, et al.
(author)
-
Childhood-onset of primary Sjögren's syndrome : phenotypic characterization at diagnosis of 158 children
- 2021
-
In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 60:10, s. 4558-4567
-
Journal article (peer-reviewed)abstract
- Objectives: To characterize the phenotypic presentation at diagnosis of childhood-onset primary SS.Methods: The Big Data Sjögren Project Consortium is an international, multicentre registry using worldwide data-sharing cooperative merging of pre-existing clinical SS databases from the five continents. For this study, we selected those patients in whom the disease was diagnosed below the age of 19 years according to the fulfilment of the 2002/2016 classification criteria.Results: Among the 12 083 patients included in the Sjögren Big Data Registry, 158 (1.3%) patients had a childhood-onset diagnosis (136 girls, mean age of 14.2 years): 126 (80%) reported dry mouth, 111 (70%) dry eyes, 52 (33%) parotid enlargement, 118/122 (97%) positive minor salivary gland biopsy and 60/64 (94%) abnormal salivary US study, 140/155 (90%) positive ANA, 138/156 (89%) anti-Ro/La antibodies and 86/142 (68%) positive RF. The systemic EULAR Sjögren's syndrome disease activity index (ESSDAI) domains containing the highest frequencies of active patients included the glandular (47%), articular (26%) and lymphadenopathy (25%) domains. Patients with childhood-onset primary SS showed the highest mean ESSDAI score and the highest frequencies of systemic disease in 5 (constitutional, lymphadenopathy, glandular, cutaneous and haematological) of the 12 ESSDAI domains, and the lowest frequencies in 4 (articular, pulmonary, peripheral nerve and CNS) in comparison with patients with adult-onset disease.Conclusions: Childhood-onset primary SS involves around 1% of patients with primary SS, with a clinical phenotype dominated by sicca features, parotid enlargement and systemic disease. Age at diagnosis plays a key role in modulating the phenotypic expression of the disease.
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Sepulveda, Jorge I. Ramirez, et al.
(author)
-
Long-term follow-up in primary Sjögren's syndrome reveals differences in clinical presentation between female and male patients
- 2017
-
In: Biology of Sex Differences. - : BioMed Central. - 2042-6410. ; 8
-
Journal article (peer-reviewed)abstract
- Background: Despite men being less prone to develop autoimmune diseases, male sex has been associated with a more severe disease course in several systemic autoimmune diseases. In the present study, we aimed to investigate differences in the clinical presentation of primary Sjogren's syndrome (pSS) between the sexes and establish whether male sex is associated with a more severe form of long-term pSS. Methods: Our study population included 967 patients with pSS (899 females and 68 males) from Scandinavian clinical centers. The mean follow-up time (years) was 8.8 +/- 7.6 for women and 8.5 +/- 6.2 for men (ns). Clinical data including serological and hematological parameters and glandular and extraglandular manifestations were compared between men and women. Results: Male patient serology was characterized by more frequent positivity for anti-Ro/SSA and anti-La/SSB (p = 0. 02), and ANA (p = 0.02). Further, men with pSS were more frequently diagnosed with interstitial lung disease (p = 0. 008), lymphadenopathy (p = 0.04) and lymphoma (p = 0.007). Conversely, concomitant hypothyroidism was more common among female patients (p = 0.009). Conclusions: We observe enhanced serological responses and higher frequencies of lymphoma-related extraglandular manifestations in men with pSS. Notably, lymphoma itself was also significantly more common in men. These observations may reflect an aggravated immune activation and a more severe pathophysiological state in male patients with pSS and indicate a personalized managing of the disease due to the influence of the sex of patients with pSS.
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| 46. |
- Thorlacius, Guðný Ella, et al.
(author)
-
Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome
- 2021
-
In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 60:2, s. 837-848
-
Journal article (peer-reviewed)abstract
- ObjectivesClinical presentation of primary Sjögren’s syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints.MethodsWe performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls.ResultsWe found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10−62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS.ConclusionTwo subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.
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| 47. |
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| 48. |
- Weissenberg, Sarah Y., et al.
(author)
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Identification and Characterization of Post-activated B Cells in Systemic Autoimmune Diseases
- 2019
-
In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
-
Journal article (peer-reviewed)abstract
- Autoimmune diseases (AID) such as systemic lupus erythematosus (SLE), primary Sjogren's syndrome (pSS), and rheumatoid arthritis (RA) are chronic inflammatory diseases in which abnormalities of B cell function play a central role. Although it is widely accepted that autoimmune B cells are hyperactive in vivo, a full understanding of their functional status in AID has not been delineated. Here, we present a detailed analysis of the functional capabilities of AID B cells and dissect the mechanisms underlying altered B cell function. Upon BCR activation, decreased spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk) phosphorylation was noted in AID memory B cells combined with constitutive co-localization of CD22 and protein tyrosine phosphatase (PTP) non-receptor type 6 (SHP-1) along with hyporesponsiveness to TLR9 signaling, a Syk-dependent response. Similar BCR hyporesponsiveness was also noted specifically in SLE CD27-B cells together with increased PTP activities and increased transcripts for PTPN2, PTPN11, PTPN22, PTPRC, and PTPRO in SLE B cells. Additional studies revealed that repetitive BCR stimulation of normal B cells can induce BCR hyporesponsiveness and that tissue-resident memory B cells from AID patients also exhibited decreased responsiveness immediately ex vivo, suggesting that the hyporesponsive status can be acquired by repeated exposure to autoantigen(s) in vivo. Functional studies to overcome B cell hyporesponsiveness revealed that CD40 co-stimulation increased BCR signaling, induced proliferation, and downregulated PTP expression (PTPN2, PTPN22, and receptor-type PTPs). The data support the conclusion that hyporesponsiveness of AID and especially SLE B cells results from chronic in vivo stimulation through the BCR without T cell help mediated by CD40-CD154 interaction and is manifested by decreased phosphorylation of BCR-related proximal signaling molecules and increased PTPs. The hyporesponsiveness of AID B cells is similar to a form of functional anergy.
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