| 1. |
- Ahmad, Awais, et al.
(författare)
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Doubtful Clinical Value of Subtyping Anti-U1-RNP Antibodies Regarding the RNP-70 kDa Antigen in Sera of Patients with Systemic Lupus Erythematosus
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:12
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Tidskriftsartikel (refereegranskat)abstract
- The detection of antinuclear antibodies is central to the diagnosis and prognosis of systemic lupus erythematosus (SLE), primary Sjogrens syndrome (pSS) and mixed connective tissue disease (MCTD). Anti-U1-RNP and anti-RNP70 antibodies were assayed in the sera of patients with SLE (n = 114), pSS (n = 54) and MCTD (n = 12). In the SLE group, 34/114 (30%) were anti-U1-RNP positive, and 21/114 (18%) were both anti-RNP70 positive and anti-U1-RNP positive. In the MCTD group, 10/12 (83%) were anti-U1-RNP positive, and 9/12 (75%) were anti-RNP70 positive. Only one individual with pSS was antibody positive (for both anti-U1-RNP and anti-RNP70). All anti-RNP70-positive samples were also anti-U1-RNP positive. Anti-U1-RNP-positive subjects with SLE were younger (p < 0.0001); showed lower concentrations of complement protein 3 (p = 0.03); had lower eosinophil (p = 0.0005), lymphocyte (p = 0.006) and monocyte (p = 0.03) counts; and had accrued less organ damage (p = 0.006) than the anti-U1-RNP-negative SLE patients. However, we observed no significant clinical or laboratory parameter differences between the anti-U1-RNP-positive individuals with/without anti-RNP70 in the SLE group. In conclusion, anti-RNP70 antibodies are not exclusive to MCTD but are rarely detected in pSS and healthy individuals. In SLE, anti-U1-RNP antibodies are associated with a clinical phenotype that resembles MCTD, with hematologic involvement and less damage accrual. Based on our results, the clinical value of subtyping anti-RNP70 in anti-U1-RNP-positive sera appears to be of limited value.
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| 2. |
- Arkema, Elizabeth V. V., et al.
(författare)
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Epidemiology and Damage Accrual of Systemic Lupus Erythematosus in Central Sweden: A Single-Center Population-Based Cohort Study Over 14 Years From ostergotland County
- 2023
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Ingår i: ACR Open Rheumatology. - : WILEY. - 2578-5745. ; 5:8, s. 426-432
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveVariations in prevalence and incidence of systemic lupus erythematosus (SLE) within a geographically defined area of central Sweden over a time period of 14 years were examined. Longitudinal differences in disease activity, laboratory test results, and damage accrual were investigated. MethodsAdults (aged & GE;18 years) residing in ostergotland County between 2008 and 2021 (mean adult population: 357,000 citizens) with confirmed SLE were identified and followed prospectively until death, December 31, 2021, or emigration. We estimated annual incidence per 100,000 inhabitants stratified by sex and age. Linear regression with year of diagnosis as the outcome assessed whether each clinical measurement at diagnosis varied over time. ResultsPrevalence on December 31, 2021, was 71.5 of 100,000 (87% female). One hundred twenty-six new cases were identified during the study period, yielding a mean annual incidence of 3.0 of 100,000 inhabitants; this was higher in females (4.8/100,000) than in males (1.2/100,000). Mean age at diagnosis was 43.7 years (SD 17.3). Age at diagnosis and disease activity measures increased over the calendar year of diagnosis (P < 0.05) whereas disease manifestations, including lupus nephritis, did not vary significantly. Accrual of organ damage was demonstrated over time since diagnosis and stratified by sex, lupus nephritis, and corticosteroid-related damage. Approximately 40% developed damage within 5 years. ConclusionSLE prevalence and incidence estimates remained constant over 14 years, and disease phenotypes at SLE onset were similar. SLE was diagnosed also among older individuals with a smaller female-to-male ratio. Estimates of prevalence and incidence were comparable to previous Scandinavian reports but lower than observed in registry data from the US and the UK.
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| 3. |
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| 4. |
- Saleh, Muna Atallah, et al.
(författare)
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Adverse Pregnancy Outcomes after Multi-Professional Follow-Up of Women with Systemic Lupus Erythematosus: An Observational Study from a Single Centre in Sweden
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- While the management of pregnant patients with systemic lupus erythematosus (SLE) has improved over the last decades, the risk of maternal, foetal, and neonatal complications is still substantial. We evaluated the occurrence of adverse pregnancy outcomes (APO) occurring in 2002-2018 among patients with SLE from the catchment area of the Department of Rheumatology in Lund, Sweden. Longitudinal clinical and laboratory data were collected and analysed. Results were stratified according to the sequence of conception. We investigated a total of 59 pregnancies in 28 patients. Prior lupus nephritis was the clinical feature that, in a multivariable regression analysis, displayed the strongest association with APO overall (OR 6.0,p= 0.02). SLE combined with antiphospholipid syndrome (APS) was associated with the risk of miscarriage (OR 3.3,p= 0.04). The positivity of multiple antiphospholipid antibodies (aPL) was associated with APO overall (OR 3.3,p= 0.05). IgG anti-cardiolipin during pregnancy resulted in a higher risk of preterm delivery (OR 6.8,p= 0.03). Hypocomplementaemia was associated with several APO, but only in the first pregnancies. We conclude that, despite the close follow-up provided, a majority of pregnancies resulted in >= 1 APO, but a few of them were severe. Our study confirms the importance of previous lupus nephritis as a main risk factor for APO in patients with SLE.
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| 5. |
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| 6. |
- Saleh, Muna Atallah, et al.
(författare)
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The prevalence of neutropenia and association with infections in patients with systemic lupus erythematosus: a Swedish single-center study conducted over 14 years
- 2024
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Ingår i: Rheumatology International. - : SPRINGER HEIDELBERG. - 0172-8172 .- 1437-160X.
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Tidskriftsartikel (refereegranskat)abstract
- Hematologic abnormalities are common manifestations of SLE, although neutropenia is observed less frequently and is not included in the classification criteria. Nonetheless, neutropenia is a risk factor for infections, especially those caused by bacteria or fungi. We aimed to evaluate the impact of neutropenia in SLE through a systematic investigation of all infections in a large cohort of well-characterized patients, focusing on neutropenia, lymphopenia, and hypocomplementemia. Longitudinal clinical and laboratory parameters obtained at visits to the Rheumatology Unit, Link & ouml;ping University Hospital, and linked data on all forms of healthcare utilization for all the subjects included in our regional SLE register during 2008-2022 were assessed. Data regarding confirmed infections were retrieved from the medical records. Overall, 333 patients were included and monitored during 3,088 visits to a rheumatologist during the study period. In total, 918 infections were identified, and 94 occasions of neutropenia (ANC < 1.5 x 10(9)/L) were detected in 40 subjects (12%). Thirty neutropenic episodes in 15 patients occurred in association with infections, of which 13 (43%) required in-hospital care, 4 (13%) needed intensive care, and 1 (3%) resulted in death. Bayesian analysis showed that patients with >= 1 occasion of neutropenia were more likely to experience one or more infections (OR = 2.05; probability of association [POA] = 96%). Both invasiveness (OR = 7.08; POA = 98%) and severity (OR = 2.85; POA = 96%) of the infections were significantly associated with the present neutropenia. Infections are common among Swedish SLE patients, 12% of whom show neutropenia over time. Importantly, neutropenia is linked to both the invasiveness and severity of infections. Awareness of the risks of severe infections in neutropenic patients is crucial to tailor therapies to prevent severe illness and death.
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| 7. |
- Saleh, Muna Atallah, et al.
(författare)
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Visual complications in patients with biopsy-proven giant cell arteritis : A population-based study
- 2016
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Ingår i: Journal of Rheumatology. - Lund : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 43:8, s. 1559-1565
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To study the clinical and laboratory characteristics of patients with biopsy-proven giant cell arteritis (GCA) with visual complications, and to evaluate the incidence rate of visual complications in GCA compared to the background population. Methods. Data from 840 patients with GCA in the county of Skane, Sweden, diagnosed between 1997 and 2010, were used for this analysis. Cases with visual complications were identified from a diagnosis registry and confirmed by a review of medical records. The rate of visual complications in patients with GCA was compared with an age-and sex-matched reference population. Results. There were 85 patients (10%) who developed ≥ 1 visual complication after the onset of GCA. Of the patients, 18 (21%) developed unilateral or bilateral complete visual loss. The mean age at diagnosis was 78 years (± 7.3); 69% were women. Compared with patients without visual complications, those with visual complication had lower C-reactive protein levels at diagnosis and were less likely to have headache, fever, and palpable abnormal temporal artery. The use of-adrenergic inhibitors was associated with visual complications. The incidence of visual complications among patients with GCA was 20.9/1000 person-years of followup compared to 6.9/1000 person-years in the reference population, resulting in a rate ratio of 3.0 (95% CI 2.3.3.8). Conclusion. Ten percent of patients with GCA developed visual complications, a rate substantially higher than that of the general population. Patients with GCA who had visual complications had lower inflammatory responses and were more likely to have been treated with 1β-adrenergic inhibitors compared with patients without visual complications.
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| 8. |
- Stockfelt, Marit, et al.
(författare)
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Plasma interferon-alpha protein levels during pregnancy are associated with lower birth weight in systemic lupus erythematosus
- 2024
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Ingår i: Rheumatology. - : OXFORD UNIV PRESS. - 1462-0324 .- 1462-0332.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Adverse pregnancy outcomes are more common in women with SLE compared with healthy women, but we lack prognostic biomarkers. Plasma IFN-alpha protein levels are elevated in a subgroup of pregnant women with SLE, but whether this is associated with pregnancy outcomes is unknown. We investigated the relationship between IFN-alpha, adverse pregnancy outcomes and the presence of autoantibodies in SLE pregnancy.Methods We followed 76 women with SLE prospectively. Protein levels of IFN-alpha were quantified in plasma collected in the second and third trimester with single-molecule array. Positivity for ANA and aPL antibodies was assessed during late pregnancy with multiplexed bead assay. Clinical outcomes included the adverse pregnancy outcomes small for gestational age (SGA), preterm birth and preeclampsia.Results During SLE pregnancy, women with SGA infants compared with those without had higher levels of plasma IFN-alpha protein, and IFN-alpha positivity was associated with lower birth weight of the infant. Preterm birth was associated with autoantibodies against chromatin. IFN-alpha protein levels associated positively with autoantibodies against chromatin, Smith/RNP (SmRNP) and RNP, but negatively with aPL antibodies.Conclusion Elevated IFN-alpha protein in plasma of women with SLE is a potential risk factor for lower birth weight of their infants. The association between IFN-alpha and lower birth weight warrants further investigation regarding the pathophysiological role of IFN-alpha during SLE pregnancy. Graphical Abstract
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| 9. |
- Torell, Agnes, 1993, et al.
(författare)
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Low CD4+T cell count is related to specific anti-nuclear antibodies, IFNα protein positivity and disease activity in systemic lupus erythematosus pregnancy.
- 2024
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Ingår i: Arthritis research & therapy. - : BioMed Central (BMC). - 1478-6362 .- 1478-6354. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Lymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features in systemic lupus erythematosus (SLE). We speculate whether lymphocyte subset counts are affected by pregnancy and if they relate to autoantibody profiles and/or IFNα protein in SLE pregnancy.Repeated blood samples were collected during pregnancy from 80 women with SLE and 51 healthy controls (HC). Late postpartum samples were obtained from 19 of the women with SLE. Counts of CD4+and CD8+T cells, B cells and NK cells were measured by flow cytometry. Positivity for anti-nuclear antibodies (ANA) fine specificities (double-stranded DNA [dsDNA], Smith [Sm], ribonucleoprotein [RNP], chromatin, Sjögren's syndrome antigen A [SSA] and B [SSB]) and anti-phospholipid antibodies (cardiolipin [CL] and β2 glycoprotein I [β2GPI]) was assessed with multiplexed bead assay. IFNα protein concentration was quantified with Single molecule array (Simoa) immune assay. Clinical data were retrieved from medical records.Women with SLE had lower counts of all lymphocyte subsets compared to HC throughout pregnancy, but counts did not differ during pregnancy compared to postpartum. Principal component analysis revealed that low lymphocyte subset counts differentially related to autoantibody profiles, cluster one (anti-dsDNA/anti-Sm/anti-RNP/anti-Sm/RNP/anti-chromatin), cluster two (anti-SSA/anti-SSB) and cluster three (anti-CL/anti-β2GPI), IFNα protein levels and disease activity. CD4+T cell counts were lower in women positive to all ANA fine specificities in cluster one compared to those who were negative, and B cell numbers were lower in women positive for anti-dsDNA and anti-Sm compared to negative women. Moreover, CD4+T cell and B cell counts were lower in women with moderate/high compared to no/low disease activity, and CD4+T cell count was lower in IFNα protein positive relative to negative women. Finally, CD4+T cell count was unrelated to treatment.Lymphocyte subset counts are lower in SLE compared to healthy pregnancies, which seems to be a feature of the disease per se and not affected by pregnancy. Our results also indicate that low lymphocyte subset counts relate differentially to autoantibody profiles, IFNα protein levels and disease activity, which could be due to divergent disease pathways.
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| 10. |
- Torell, Agnes, 1993, et al.
(författare)
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Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus.
- 2023
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Ingår i: Arthritis research & therapy. - : BMC. - 1478-6362 .- 1478-6354. ; 25
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Tidskriftsartikel (refereegranskat)abstract
- An increased risk of pregnancy complications is seen in women with systemic lupus erythematosus (SLE), but the specific immunopathological drivers are still unclear. Hallmarks of SLE are granulocyte activation, type I interferon (IFN) overproduction, and autoantibodies. Here we examined whether low-density granulocytes (LDG) and granulocyte activation increase during pregnancy, and related the results to IFNα protein levels, autoantibody profile, and gestational age at birth.Repeated blood samples were collected during pregnancy in trimesters one, two, and three from 69 women with SLE and 27 healthy pregnant women (HC). Nineteen of the SLE women were also sampled late postpartum. LDG proportions and granulocyte activation (CD62L shedding) were measured by flow cytometry. Plasma IFNα protein concentrations were quantified by single molecule array (Simoa) immune assay. Clinical data were obtained from medical records.Women with SLE had higher LDG proportions and increased IFNα protein levels compared to HC throughout pregnancy, but neither LDG fractions nor IFNα levels differed during pregnancy compared to postpartum in SLE. Granulocyte activation status was higher in SLE relative to HC pregnancies, and it was increased during pregnancy compared to after pregnancy in SLE. Higher LDG proportions in SLE were associated with antiphospholipid positivity but not to IFNα protein levels. Finally, higher LDG proportions in trimester three correlated independently with lower gestational age at birth in SLE.Our results suggest that SLE pregnancy results in increased peripheral granulocyte priming, and that higher LDG proportions late in pregnancy are related to shorter pregnancy duration but not to IFNα blood levels in SLE.
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