| 1. |
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| 2. |
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| 4. |
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| 5. |
- Biazar, C., et al.
(author)
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Cutaneous lupus erythematosus : First multicenter database analysis of 1002 patients from the European Society of Cutaneous Lupus Erythematosus (EUSCLE)
- 2013
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In: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972 .- 1873-0183. ; 12:3, s. 444-454
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Research review (peer-reviewed)abstract
- In this prospective, cross-sectional, multicenter study, we assessed clinical and laboratory characteristics from patients with cutaneous lupus erythematosus (CLE) using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). 1002 (768 females, 234 males) patients with different subtypes of CLE, such as acute CLE (ACLE, 304 patients), subacute CLE (SCLE, 236 patients), chronic CLE (CCLE, 397 patients), and intermittent CLE (ICLE, 65 patients), from 13 European countries were collected and statistically analyzed by an SPSS database. The main outcome measures included gender, age at onset of disease, LE-specific and LE-nonspecific skin lesions, photosensitivity, laboratory features, and the criteria of the American College of Rheumatology (ACR) for the classification of systemic lupus erythematosus. The mean age at onset of disease was 43.0±15.7 years and differed significantly between the CLE subtypes. In 347 (34.6%) of the 1002 patients, two or more CLE subtypes were diagnosed during the course of the disease and 453 (45.2%) presented with LE-nonspecific manifestations. Drug-induced CLE and SjögrenD́s Syndrome had the highest prevalence in SCLE patients (13.1% and 14.0%, respectively). Photosensitivity was significantly more frequent in patients with ACLE, SCLE, and ICLE compared with those with CCLE. The detection of antinuclear antibodies such as anti-Ro/SSA and anti-La/SSB antibodies revealed further significant differences between the CLE subtypes. In summary, the EUSCLE Core Set Questionnaire and its database facilitate the analysis of clinical and laboratory features in a high number of patients with CLE and will contribute to standardized assessment and monitoring of the disease in Europe.
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| 6. |
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| 10. |
- Damoiseaux, Jan, et al.
(author)
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Autoantibodies and SARS-CoV2 infection : The spectrum from association to clinical implication. Report of the 15th Dresden Symposium on Autoantibodies
- 2022
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In: Autoimmunity Reviews. - : Elsevier. - 1568-9972 .- 1873-0183. ; 21:3
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Research review (peer-reviewed)abstract
- The relation between infections and autoimmune diseases has been extensively investigated. Multiple studies suggest a causal relation between these two entities with molecular mimicry, hyperstimulation and dysregulation of the immune system as plausible mechanisms. The recent pandemic with a new virus, i.e., SARS-CoV-2, has resulted in numerous studies addressing the potential of this virus to induce autoimmunity and, eventually, autoimmune disease. In addition, it has also revealed that pre-existing auto-immunity (auto-Abs neutralizing type I IFNs) could cause life-threatening disease. Therefore, the topic of the 15th Dresden Symposium on Autoantibodies was focused on autoimmunity in the SARS-CoV-2 era. This report is a collection and distillation of the topics presented at this meeting.
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| 11. |
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| 12. |
- Einstein, Ofira, et al.
(author)
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Physical exercise therapy for autoimmune neuroinflammation : Application of knowledge from animal models to patient care.
- 2022
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In: Autoimmunity Reviews. - : Elsevier. - 1568-9972 .- 1873-0183. ; 21:4
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Journal article (peer-reviewed)abstract
- Physical exercise (PE) impacts various autoimmune diseases. Accordingly, clinical trials demonstrated the safety of PE in multiple sclerosis (MS) patients and indicated beneficial outcomes. There is also an increasing body of research on the beneficial effects of exercise on experimental autoimmune encephalomyelitis (EAE), the animal model of MS, and various mechanisms underlying these effects were suggested. However, despite the documented favorable impact of PE on our health, we still lack a thorough understanding of its effects on autoimmune neuroinflammation and specific guidelines of PE therapy for MS patients are lacking. To that end, current findings on the impact of PE on autoimmune neuroinflammation, both in human MS and animal models are reviewed. The concept of personalized PE therapy for autoimmune neuroinflammation is discussed, and future research for providing biological rationale for clinical trials to pave the road for precise PE therapy in MS patients is described.
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| 13. |
- Elrashdy, Fatma, et al.
(author)
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Autoimmunity roots of the thrombotic events after COVID-19 vaccination
- 2021
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In: Autoimmunity Reviews. - : Elsevier. - 1568-9972 .- 1873-0183. ; 20:11
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Research review (peer-reviewed)abstract
- Although vaccination represents the most promising way to stop or contain the coronavirus disease 2019 (COVID-19) pandemic and safety and effectiveness of available vaccines were proven, a small number of individuals who received anti-SARS-CoV-2 vaccines developed a prothrombotic syndrome. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can be triggered by the adenoviral vector-based vaccine, whereas lipid nanoparticle-mRNA-based vaccines can induce rare cases of deep vein thrombosis (DVT). Although the main pathogenic mechanisms behind this rare phenomenon have not yet been identified, both host and vaccine factors might be involved, with pathology at least in part being related to the vaccine-triggered autoimmune reaction. In this review, we are considering some aspects related to pathogenesis, major risk factors, as well as peculiarities of diagnosis and treatment of this rare condition.
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| 14. |
- Gauckler, Philipp, et al.
(author)
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Rituximab in adult minimal change disease and focal segmental glomerulosclerosis - What is known and what is still unknown?
- 2020
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In: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972 .- 1873-0183. ; 19:11
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Research review (peer-reviewed)abstract
- Primary forms of minimal change disease and focal segmental glomerulosclerosis are rare podocytopathies and clinically characterized by nephrotic syndrome. Glucocorticoids are the cornerstone of the initial immunosuppressive treatment in these two entities. Especially among adults with minimal change disease or focal segmental glomerulosclerosis, relapses, steroid dependence or resistance are common and necessitate re-initiation of steroids and other immunosuppressants. Effective steroid-sparing therapies and introduction of less toxic immunosuppressive agents are urgently needed to reduce undesirable side effects, in particular for patients whose disease course is complex. Rituximab, a B cell depleting monoclonal antibody, is increasingly used off-label in these circumstances, despite a low level of evidence for adult patients. Hence, critical questions concerning drug-safety, long-term efficacy and the optimal regimen for rituximab-treatment remain unanswered. Evidence in the form of large, multicenter studies and randomized controlled trials are urgently needed to overcome these limitations.
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| 15. |
- Giannopoulou, Nefeli, et al.
(author)
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COVID-19 vaccine safety during pregnancy in women with systemic lupus erythematosus
- 2023
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In: Autoimmunity Reviews. - : Elsevier. - 1568-9972 .- 1873-0183. ; 22:4
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Journal article (peer-reviewed)abstract
- COVID-19 vaccination has been shown to be safe in patients with systemic lupus erythematosus (SLE), but data on vaccine-associated adverse events (AEs) during the antenatal and lactation period are scarce or lacking. We investigated COVID-19 vaccination-related AEs in pregnant SLE patients from the COVAD study, a global esurvey involving 157 collaborators from 106 countries. A total of 9201 complete responses were extracted. Among 6787 (73.8%) women, we identified 70 (1.1%) who were exposed to at least one COVID-19 vaccine dose during pregnancy, 11 with SLE. Delayed onset (>7 days) vaccine-related AEs were triangulated with disease activity, treatment changes due to flare after vaccination, and COVID-19 infections in vaccinated pregnant women. Health-related quality of life and physical function was recorded using PROMIS. Age of patients ranged from 28 to 39 years; 5/11 women were of Asian origin. None of these patients reported major vaccine AEs or change in the status of their autoimmune disease. Although minor AEs were common, they did not impair daily functioning, and the symptoms resolved after a median of 3 (IQR: 2.5-5.0) days. All patients reported good to excellent health status. No adverse pregnancy outcomes were reported. Importantly, none of the patients reported thrombotic events post-vaccination, which provides reassurance in a patient population with a high risk for cardiovascular comorbidity and thrombosis, especially in the presence of antiphospholipid antibodies or the antiphospholipid syndrome, a considerable portion of SLE patients. Our findings provide reassurance and can contribute to informed decisions regarding vaccination in patients with SLE and highrisk pregnancies due to their background autoimmune disease. The risk/benefit ration of COVID-19 vaccination appears favourable, with vaccines both providing passive immunisation to the fetus and active immunisation to the mother with no signals of exacerbation of the mother's autoimmune disease.
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| 16. |
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| 17. |
- Gomez, Alvaro, et al.
(author)
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Do biological agents improve health-related quality of life in patients with systemic lupus erythematosus? Results from a systematic search of the literature
- 2022
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In: Autoimmunity Reviews. - : Elsevier. - 1568-9972 .- 1873-0183. ; 21:11
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Research review (peer-reviewed)abstract
- Despite an unprecedented rise in the number of biological therapies developed for systemic lupus erythematosus (SLE) during the last decades, most randomised clinical trials (RCTs) have failed to reach their primary efficacy endpoint. These endpoints mainly constitute composite outcomes that encompass disease activity indices derived from clinician-reported and laboratory data and do not necessarily reflect the patient perspective, as symptoms that represent major concerns to patients, such as fatigue, are seldom part of the evaluation. To overcome this limitation, patient-reported outcomes (PROs) constitute useful tools for evaluating the effect of an intervention on facets that are particularly relevant for the patients. In the present review, we performed a systematic literature search aiming to examine the effect of biological therapies on SLE patients' health-related quality of life (HRQoL) and fatigue in RCT and real-life settings. We summarised results concerning 14 different biological agents, the majority of which targeting B cells or type I interferons, and discuss strategies that have been used to analyse HRQoL data, putting emphasis on minimal clinically important differences and the potential use of PROs as distinct targets in treat-to-target approaches. Lastly, we discuss differences between generic and disease-specific PRO measures and highlight the need of using a combination thereof aiming to capture the patient perspective in a comprehensive manner.
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| 18. |
- Gravina, Giacomo, et al.
(author)
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Survivin in autoimmune diseases.
- 2017
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In: Autoimmunity reviews. - : Elsevier BV. - 1873-0183 .- 1568-9972. ; 16:8, s. 845-855
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Research review (peer-reviewed)abstract
- Survivin is a protein functionally important for cell division, apoptosis, and possibly, for micro-RNA biogenesis. It is an established marker of malignant cell transformation. In non-malignant conditions, the unique properties of survivin make it indispensable for homeostasis of the immune system. Indeed, it is required for the innate and adaptive immune responses, controlling differentiation and maintenance of CD4(+) and CD8(+) memory T-cells, and in B cell maturation. Recently, survivin has emerged as an important player in the pathogenesis of autoimmune diseases. Under the conditions of unreserved inflammation, survivin enhances antigen presentation, maintains persistence of autoreactive cells, and supports production of autoantibodies. In this context, survivin takes its place as a diagnostic and prognostic marker in rheumatoid arthritis, psoriasis, systemic sclerosis and pulmonary arterial hypertension, neuropathology and multiple sclerosis, inflammatory bowel diseases and oral lichen planus. In this review, we summarise the knowledge about non-malignant properties of survivin and focus on its engagement in cellular and molecular pathology of autoimmune diseases. The review highlights utility of survivin measures for clinical applications. It provides rational for the survivin inhibiting strategies and presents results of recent reports on survivin inhibition in modern therapies of cancers and autoimmune diseases.
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| 19. |
- Groen, Solveig Skovlund, et al.
(author)
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Exploring IL-17 in spondyloarthritis for development of novel treatments and biomarkers
- 2021
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In: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972. ; 20:3
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Research review (peer-reviewed)abstract
- Spondyloarthritis (SpA) is an umbrella term describing a family of chronic inflammatory rheumatic diseases. These diseases are characterised by inflammation of the axial skeleton, peripheral joints, and entheseal insertion sites throughout the body which can lead to structural joint damage including formation of axial syndesmophytes and peripheral osteophytes. Genetic evidence, preclinical and clinical studies indicate a clear role of interleukin (IL)- 23 and IL-17 as mediators in SpA pathogenesis. Targeting the IL-23/−17 pathways seems an efficient strategy for treatment of SpA patients, and despite the remaining challenges the pathway holds great promise for further advances and improved therapeutic opportunities. Much research is focusing on serological markers and imaging strategies to correctly diagnose patients in the early stages of SpA. Biomarkers may facilitate personalised medicine tailored to each patient's specific disease to optimise treatment efficacy and to monitor therapeutic response. This narrative review focuses on the IL-17 pathway in SpA-related diseases with emphasis on its role in pathogenesis, current approved IL-17 inhibitors, and the need for biomarkers reflecting core disease pathways for early diagnosis and measurement of disease activity, prognosis, and response to therapy.
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| 20. |
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| 21. |
- Havarinasab, Said, et al.
(author)
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Organic mercury compounds and autoimmunity
- 2005
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In: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972 .- 1873-0183. ; 4:5, s. 270-275
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Research review (peer-reviewed)abstract
- Based on in vitro studies and short-term in vivo studies, all mercurials were for a long time considered as prototypic immunosuppressive substances. Recent studies have confirmed that organic mercurials such as methyl mercury (MeHg) and ethyl mercury (EtHg) are much more potent immunosuppressors than inorganic mercury (Hg). However, Hg interacts with the immune system in the presence of a susceptible genotype to cause immunostimulation, antinucleolar antibodies targeting fibrillarin, and systemic immune-complex (IC) deposits, a syndrome called Hg-induced autoimmunity (HgIA). Recent studies in mice with a susceptible genotype has revealed that the immunosuppressive effect of MeHg and EtHg will within 1-3 weeks be superseded by immunostimulation causing an HgIA-like syndrome. At equimolar doses of Hg, MeHg has the weakest immunostimulating, autoimmunogen, and IC-inducing effect, while the effect of thimerosal is similar to that of inorganic mercury. The immunosuppression is caused by the organic mercurials per se. Since they undergo rapid transformation to inorganic Hg, studies are being undertaken to delineate the importance of the organic substances per se and the newly formed inorganic Hg for induction of autoimmunity. © 2004 Elsevier B.V. All rights reserved.
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| 22. |
- Heijstek, M W, et al.
(author)
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Vaccination in paediatric patients with auto-immune rheumatic diseases: A systemic literature review for the European League against Rheumatism evidence-based recommendations.
- 2011
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In: Autoimmunity reviews. - : Elsevier BV. - 1873-0183 .- 1568-9972. ; 11:2, s. 112-122
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To analyze available evidence on vaccinations in paediatric patients with rheumatic and autoinflammatory diseases. This evidence formed the basis of the recently constructed European League against Rheumatism (EULAR) recommendations for vaccination of these patients. METHODS: A systematic literature review in the MEDLINE and EMBASE databases was conducted using various terms for vaccinations, paediatric rheumatic and autoinflammatory diseases and immunosuppressive drugs. Only papers on paediatric patients (<18years of age) were selected. A panel of 13 experts in the field graded methodological quality and extracted data using predefined criteria. RESULTS: 27 papers were available. No studies were found on autoinflammatory diseases. 14 studies considered live-attenuated vaccines. Evidence so far supports the safety and immunogenicity of non-live composite vaccines, although studies were underpowered to accurately assess safety. Live-attenuated vaccines did not cause disease flares or severe adverse events, not even in patients on methotrexate and low dose glucocorticosteroids. Seven patients on anti-TNFalpha therapy were described receiving the live-attenuated measles, mumps, rubella (n=5) or varicella (n=2) booster without severe adverse events. CONCLUSIONS: Data on safety and efficacy of vaccinations in paediatric patients with rheumatic diseases is reassuring, but too limited to draw definite conclusions. More research is needed on the safety and efficacy of especially live-attenuated vaccines in patients with rheumatic and autoinflammatory diseases using high dose immunosuppressive drugs.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Kronbichler, Andreas, et al.
(author)
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The COVID-19 pandemic and ANCA-associated vasculitis - reports from the EUVAS meeting and EUVAS education forum
- 2021
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In: Autoimmunity Reviews. - : Elsevier. - 1568-9972 .- 1873-0183. ; 20:12
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Research review (peer-reviewed)abstract
- The Coronavirus Disease 2019 (COVID-19) pandemic influenced the management of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A paucity of data exists on outcome of patients with vasculitis following COVID-19, but mortality is higher than in the general population and comparable to patients undergoing haemodialysis or kidney transplant recipients (reported mortality rates of 20-25%). Delays in diagnosis have been reported, which are associated with sequelae such as dialysis-dependency. Management of ANCA-associated vasculitis has not changed with the aim to suppress disease activity and reduce burden of disease. The use of rituximab, an important and widely used agent, is associated with a more severe hospital course of COVID-19 and absence of antibodies following severe acute respiratory syndrome (SARS)-CoV-2 infections, which prone patients to re-infection. Reports on vaccine antibody response are scarce at the moment, but preliminary findings point towards an impaired immune response, especially when patients receive rituximab as part of their treatment. Seropositivity was reported in less than 20% of patients when rituximab was administered within the prior six months, and the antibody response correlated with CD19+ B-cell repopulation. A delay in maintenance doses, if disease activity allows, has been suggested using a CD19+ B-cell guided strategy. Other immunosuppressive measures, which are used in ANCA-associated vasculitis, also impair humoral and cellular vaccine responses. Regular measurements of vaccine response or a healthcare-policy time-based strategy are indicated to provide additional doses ("booster") of COVID-19 vaccines. This review summarizes a recent educational forum and a recent virtual meeting of the European Vasculitis Society (EUVAS) focusing on COVID-19.
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| 27. |
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| 28. |
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| 29. |
- Marta, Monica, et al.
(author)
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Regulation of autoimmune encephalomyelitis by toll-like receptors
- 2009
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In: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972 .- 1873-0183. ; 8:6, s. 506-509
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Journal article (peer-reviewed)abstract
- Experimental autoimmune encephalomyelitis (EAE) is a Th17-mediated autoimmune disease and an animal model for multiple sclerosis (MS). Complete Freund's adjuvant (CFA) contains pathogen-associated molecular patterns (PAMPs) that bind toll-like receptors (TLRs), and is necessary to induce EAE. Upstream TLR signals modify innate and adaptive immune responses in EAE. In detail, the common TLR adaptor molecule MyD88 is necessary for induction of EAE, and mediates activation of peripheral myeloid dendritic cells (mDCs) and differentiation of autoimmune Th17 cells. The stimulatory TLRs have not yet been identified for Th17 cells. TLR4 down regulates disease severity in EAE and Th17 cell responses, but promotes Th1 cell responses, which may inhibit the differentiation of Th17 cells. Moreover, treatment with a TLR4 ligand tolerizes mice and prevents EAE. TLR9 down regulates disease severity in myelin oligodendrocyte glycoprotein (MOG)-induced EAE, whereas it promotes disease in MOG(35-55)-induced EAE. Thus MyD88, TLR4 and TLR9 modify the disease process in EAE. Both endogenous and CFA-derived TLR ligands are implicated to modulate the disease process.
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| 30. |
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| 31. |
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| 32. |
- Moiseev, Sergey, et al.
(author)
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2020 international consensus on ANCA testing beyond systemic vasculitis
- 2020
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In: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972. ; 19:9
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Research review (peer-reviewed)abstract
- This document follows up on a 2017 revised international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance. Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCA-associated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn's disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered.
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| 33. |
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| 34. |
- Nagy, E., et al.
(author)
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The impact of the COVID-19 pandemic on autoimmune diagnostics in Europe: A lesson to be learned
- 2021
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In: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972. ; 20:12
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Journal article (peer-reviewed)abstract
- Introduction: The first wave of COVID-19 pandemic has disrupted almost all areas of the health care services to some extent throughout the world. Although the negative impact of COVID-19 on patients with autoimmune diseases has also been recognized, available data in this regard are limited. In the current study of the European Autoimmunity Standardisation Initiative (EASI) we aimed to provide reliable data on the extent of the impact of COVID-19 pandemic on test requests for different autoantibodies in European countries. Methods: Data on test numbers and on the number of positive results were collected in 97 clinical laboratories from 15 European countries on a monthly basis for the year before (2019) and the year during (2020) the COVID19 pandemic. Results: A reduction in the number of autoantibody tests was observed in all European countries in the year 2020 compared to 2019. The reduction affected all autoantibody tests with an overall decrease of 13%, ranging from 1.4% (Switzerland) to 25.5% (Greece). In all countries, the decrease was most pronounced during the first wave of the pandemic (March-May 2020) with an overall decrease in those three months of 45.2%. The most affected autoantibodies were those commonly requested by general practitioners (anti-tTG IgA (71%), RF IgM (66%) and ACPA (61%)). In the second wave of the pandemic (October-December 2020) the decrease was less pronounced (6.8%). With respect to the rate of positive results, subtle differences were observed for distinct autoantibodies during the pandemic, but the total rate of positive results was similar in both years. Conclusions: Our study demonstrated a strong decrease in autoantibody requests during the first wave of the COVID-19 pandemic in 15 European countries. The second wave was characterized by a less pronounced impact, with some participating countries hardly affected, while some other countries experienced a second decline. The decrease was clearly associated with the level of lock-down and with the required adjustments in the health care systems in different countries, supporting the importance of an effective strategy for the coordination of autoimmune testing in challenging situations as the COVID-19 pandemic.
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| 35. |
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| 36. |
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| 37. |
- Parodis, Ioannis, 1981-, et al.
(author)
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Is per-protocol kidney biopsy required in lupus nephritis?
- 2024
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In: Autoimmunity Reviews. - : Elsevier. - 1568-9972 .- 1873-0183. ; 23:1
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Research review (peer-reviewed)abstract
- Baseline kidney biopsy is recommended in lupus nephritis (LN). Biopsy allows to classify different forms of LN and differentiate other forms of renal involvement, such as tubulo-interstitial nephritis or thrombotic microangiopathy. The indications for repeat biopsy are more controversial. Some authors feel that good clinical monitoring is sufficient to assess prognosis and make therapeutic decisions. Based on the recently demonstrated discordance between clinical and histological response, some physicians recommend per-protocol biopsies either at 6 months in stable patients to verify the response to induction therapy, or after one-to-two years to assess treatment efficacy and tune the duration of maintenance therapy. Others recommend repeating kidney biopsy in case of incomplete response or to discriminate between active and chronic lesions. By definition, a per-protocol kidney biopsy differs from a repeat biopsy in that the former is foreseen at fixed timepoints, regardless of the clinical response. Although any decision should always consider the patient's overall clinical condition, there are no doubts that repeat kidney biopsy represents a useful tool in difficult cases to evaluate treatment response, modulate treatment intensity, and predict long-term renal outcome both in quiescent lupus and during flares. How to harmonize per-protocol biopsies in the LN course remains challenging.
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| 38. |
- Parodis, Ioannis, et al.
(author)
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Smoking and pre-existing organ damage reduce the efficacy of belimumab in systemic lupus erythematosus.
- 2017
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In: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972 .- 1873-0183. ; 16:4, s. 343-351
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: Belimumab is the first biologic drug approved for Systemic Lupus Erythematosus (SLE). Here, we aimed to investigate the effects of belimumab on clinical and serologic outcomes, and sought to identify predictors of treatment response in three Swedish real-life settings.METHODS: Fifty-eight patients were enrolled at initiation of belimumab and followed longitudinally for up to 53months. Surveillance outcomes included the SLE Disease Activity Index 2000 (SLEDAI-2K), 100mm Visual Analogue Scales for Physician's Global Assessment (PGA), fatigue, pain and general health, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Assessment of treatment response included the SLE responder index (SRI). B lymphocyte stimulator (BLyS) levels were determined using ELISA.RESULTS: SLEDAI-2K (median baseline score: 8.0; IQR: 4.0-13.8), PGA and corticosteroid use decreased during therapy, and patients reported improvements on fatigue, pain, and general health (p<0.0001 for all). SDI scores remained stable (p=0.08). Patients with baseline SDI scores >1 showed decreased probability and prolonged time to attain SRI response (HR: 0.449; 95% CI: 0.208-0.967), as did current smokers compared with non-smokers (HR: 0.103; 95% CI: 0.025-0.427). In contrast, baseline BLyS levels ≥1.2ng/mL predicted increased probability and shorter time to attain SRI response (HR: 2.566; 95% CI: 1.222-5.387).CONCLUSIONS: Disease activity and corticosteroid usage decreased, patient-reported outcomes improved, and no significant organ damage was accrued during follow-up. Smoking and organ damage predicted reduced treatment efficacy. These findings might contribute to a better selection of patients who are likely to benefit from belimumab.
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| 39. |
- Parodis, Ioannis, 1981-, et al.
(author)
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When should targeted therapies be used in the treatment of lupus nephritis : Early in the disease course or in refractory patients?
- 2024
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In: Autoimmunity Reviews. - : Elsevier. - 1568-9972 .- 1873-0183. ; 23:1
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Research review (peer-reviewed)abstract
- Although the prognosis of lupus nephritis (LN) has improved over the last few decades, 5-20% of patients still progress to kidney failure. Hence, there is an unmet need to improve the management of LN. Two novel drugs, belimumab and voclosporin, have been recently approved for LN and obinutuzumab is in the late stage of development. In randomised controlled trials (RCTs), all these drugs, added to the standard-of-care, were more effective than standard-of-care alone in achieving renal response. Now the question is: should these new drugs be used early in the disease course or just in refractory patients? The main reasons supporting the early use are based on the RCTs that demonstrated benefits when combinatory regimen was initiated early in incident and relapsing patients leading to a higher proportion of patients to achieve renal response, hence reducing nephron loss and the risk of kidney failure. The main reasons supporting the use of the combinatory regimens primarily in relapsing/refractory patients acknowledge that many patients responded well even without add-on medications, allowing a more economic use of innovative and costly drugs. However, good predictors of renal response to standard-of-care are lacking and, thus, the decision of adding new treatments early or just in refractory or relapsing patients has to consider drug access, risks of over or undertreatment, and preservation of kidney function in high-risk individuals.
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| 40. |
- Pollard, K Michael, et al.
(author)
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Immunology and genetics of induced systemic autoimmunity
- 2005
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In: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972 .- 1873-0183. ; 4:5, s. 282-288
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus is a multigenic disorder of unknown etiology. To investigate the role of specific genes in lupus, we have examined the effects of single gene deletions on mercury-induced autoimmunity. Deficiency of certain genes abrogated induction of autoimmunity, while absence of others had little effect. The most interesting observations were obtained with genes related to interferon-γ. Genes involved in upregulation of IFN-γ expression did not significantly influence autoimmunity whereas absence of IFN-γ or IFN-γ receptor led to greatly reduced autoantibody responses and immunopathology. Absence of IRF-1, a gene expressed in response to IFN-γ, resulted in selective retention of anti-chromatin autoantibodies demonstrating that specific defects in signaling pathways and gene expression subsequent to IFN-γ/IFN-γ receptor interaction influence specific disease parameters. These studies show that single gene deletions can have various outcomes ranging from no effect, suppression of one or more features of disease, to suppression of all features of disease, and that all three outcomes can be observed in the IFN-γ pathway. IFN-γ influences the expression and function of other lupus relevant genes such as IL-6 and β2microglobulin, therefore the effects of these gene deletions on disease expression may also reflect responses downstream of IFN-γ function. © 2005 Elsevier B.V. All rights reserved.
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| 41. |
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| 42. |
- Rönnelid, Johan, et al.
(author)
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Use of a commercial line blot assay as a screening test for autoantibodies in inflammatory myopathies
- 2009
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In: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972 .- 1873-0183. ; 9:1, s. 58-61
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Journal article (peer-reviewed)abstract
- AIMS: To evaluate the clinical utility of a commercial immunoblot assay for the detection of myositis-specific autoantibodies. METHODS: Serum samples from 153 myositis patients and 77 disease controls were investigated. The commercial Euroline assay with seven autoantigens (Mi-2, Ku, PM-Scl, Jo-1, Pl-7, Pl-12 and SSA/Ro-52) was used according to the manufacturer s instructions, and supplemented with an anti-SRP strip. In a separate experiment analyses were performed at different temperatures. Results were recorded with densitometry. RESULTS: Anti-Jo-1 was found in 18 myositis and one systemic sclerosis patient. Antibodies against Mi-2 were found in 5 myositis patients, and eleven myositis patients had antibodies against PM-Scl. Four myositis patients showed anti-Pl-7 reactivity, whereas no patients had antibodies against Pl-12. Anti-Ku antibodies were found in 4 myositis and 2 primary Sjögren's syndrome patients. Anti-SRP was found in 8 myositis patients as well as in two disease controls. Antibodies against SSA/Ro52 ranged between 23-62% in all groups except juvenile dermatomyositis patients. Most autoantibody reactivities were clearly positive, only 11% (14/127) were borderline positive. Higher assay temperature increased antibody reactivities. CONCLUSIONS: Except for anti-SSA/Ro-52 and anti-Ku the antibody reactivities were rather myositis-specific, supporting the use of this immunoblot assay. However, assay validation needs to be determined against other methods.
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| 43. |
- Segelmark, Mårten, et al.
(author)
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Autoimmune kidney diseases.
- 2010
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In: Autoimmunity Reviews. - : Elsevier BV. - 1873-0183 .- 1568-9972. ; 9, s. 366-371
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Journal article (peer-reviewed)abstract
- The second most common cause of chronic renal failure is glomerulonephritis, which is a collective term used for numerous diseases with the common denominator of histological renal inflammation emanating from the glomerular tuft. Whether all forms of glomerulonephritis should be considered as autoimmune disease is debatable, but immune mechanisms are important in all of them. This review focuses on four relatively well delineated forms of primary glomerulonephritis: Goodpastures or anti-GBM disease, IgA nephritis, membranous nephropathy and membranoproliferative glomerulonephritis. The autoantibodies are directed either to molecules within the glomeruli, such as the glomerular basement membrane in anti-GBM disease and to the podocytes in membranous glomerulonephritis, or to components of the immune system such as C3 convertase in membranoproliferative glomerulonephritis and IgA in IgA nephritis. Differences in diagnostic practices and classification controversies obscure comparative epidemiological studies, but there seem to be huge differences between incidence rates between countries and over time, both genetic factors and infections seem to matter but strong indications for a role of other environmental factors are still lacking.
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| 44. |
- Segelmark, Mårten, et al.
(author)
-
Autoimmune kidneydisease
- 2010
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In: Autoimmunity Reviews. - Philadelphia, PA, United States : Elsevier. - 1568-9972 .- 1873-0183. ; 9:5, s. A366-A371
-
Journal article (peer-reviewed)abstract
- The second most common cause of chronic renal failure is glomerulonephritis, which is a collective term used for numerous diseases with the common denominator of histological renal inflammation emanating from the glomerular tuft. Whether all forms of glomerulonephritis should be considered as autoimmune disease is debatable, but immune mechanisms are important in all of them. This review focuses on four relatively well delineated forms of primary glomerulonephritis: Goodpastures or anti-GBM disease, IgA nephritis, membranous nephropathy and membranoproliferative glomerulonephritis. The autoantibodies are directed either to molecules within the glomeruli, such as the glomerular basement membrane in anti-GBM disease and to the podocytes in membranous glomerulonephritis, or to components of the immune system such as C3 convertase in membranoproliferative glomerulonephritis and IgA in IgA nephritis. Differences in diagnostic practices and classification controversies obscure comparative epidemiological studies, but there seem to be huge differences between incidence rates between countries and over time, both genetic factors and infections seem to matter but strong indications for a role of other environmental factors are still lacking.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Smith, Vanessa, et al.
(author)
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Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud's phenomenon and systemic sclerosis
- 2020
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In: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972. ; 19:3
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Research review (peer-reviewed)abstract
- Capillaroscopy is a non-invasive and safe tool which allows the evaluation of the morphology of the microcirculation. Since its recent incorporation in the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for systemic sclerosis together with its assessed role to monitor disease progression, capillaroscopy became a ‘mainstream’ investigation for rheumatologists. Given its increasing use by a variety of physicians internationally both in daily practice to differentiate primary from secondary Raynaud's phenomenon, as well as in research context to predict disease progression and monitor treatment effects, standardisation in capillaroscopic image acquisition and analysis seems paramount. To step forward to this need, experts in the field of capillaroscopy/microcirculation provide in this very consensus paper their view on image acquisition and analysis, different capillaroscopic techniques, normal and abnormal capillaroscopic characteristics and their meaning, scoring systems and reliability of image acquisition and interpretation.
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| 49. |
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| 50. |
- van Assen, S., et al.
(author)
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Vaccination in adult patients with auto-immune inflammatory rheumatic diseases: A systematic literature review for the European League Against Rheumatism evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases
- 2011
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In: Autoimmunity Reviews. - : Elsevier BV. - 1873-0183 .- 1568-9972. ; 10:6, s. 341-352
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Research review (peer-reviewed)abstract
- Objectives: To present the systematic literature review (SLR), which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD). Methods: AIIRD, vaccines and immunomodulating drugs, as well as eight key questions were defined by the multidisciplinary expert committee commissioned by EULAR for developing the recommendations. A SLR was performed using MedLine through October 2009 and including data from meta-analyses, systematic reviews, randomized trials, and observational studies, excluding case series with participants. Articles in English and regarding patients years of age, were eligible. Results: Several vaccine-preventable infections (VPI) occur more often in AIIRD-patients and most vaccines are efficacious in AIIRD-patients, even when treated with immunomodulating agents, except rituximab. There does not appear to be an increase in vaccination-related harms in vaccinated patients with AIIRD in comparison with unvaccinated patients with AIIRD. However, these studies are underpowered and therefore not conclusive. Conclusion: Based on the current evidence from the literature, recommendations for vaccination in patients with AIIRD were made. However, more research is needed in particular regarding incidence of VPI, harms of vaccination and the influence of (new and established) immunomodulating agents on vaccination efficacy. (C) 2011 Elsevier B.V. All rights reserved.
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