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- Wirestam, Lina, 1986-, et al.
(författare)
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Osteopontin and disease activity in patients with recent-onset systemic Lupus Erythematosus : Results from the SLICC Inception Cohort
- 2019
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 46:5, s. 492-500
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Tidskriftsartikel (refereegranskat)abstract
- Objective. In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes. Methods. We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively. Results. Compared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01). Conclusion. The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.
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| 2. |
- Ambrosi, Aurelie, et al.
(författare)
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Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern
- 2012
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 71:3, s. 334-340
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Tidskriftsartikel (refereegranskat)abstract
- Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. less thanbrgreater than less thanbrgreater thanMethods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. less thanbrgreater than less thanbrgreater thanResults There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (pandlt;0.05). Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (pandlt;0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. less thanbrgreater than less thanbrgreater thanConclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.
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| 5. |
- Eriksson, Per, et al.
(författare)
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Improved outcome in Wegener's granulomatosis and microscopic polyangiitis? A retrospective analysis of 95 cases in two cohorts
- 2009
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 265:4, s. 496-506
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Tidskriftsartikel (refereegranskat)abstract
- Mortality rates for Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) have decreased after the introduction of cyclophosphamide. Standardized mortality ratio (SMR) expresses the overall mortality of patients compared with the general population. The aims of this study were to compare survival in an old and a recent cohort of patients with WG and MPA using SMR and to determine predictors for death in both groups combined. Survival analyses were performed by Kaplan-Meier survival curves, SMR and proportional hazards regression models. The nephrology and rheumatology clinics at Linkoping University Hospital, Sweden. All patients diagnosed with WG or MPA in the catchment area during 1978-2005 were divided into two cohorts; patients diagnosed before (n = 32, old cohort) and after (n = 63, recent cohort) December 31, 1996. The two cohorts differed regarding the proportion of WG (75% vs. 56%, P = 0.03) and a tendency for more pronounced kidney involvement in the old cohort: 266 mu mol L-1 (16% dialysis-dependent) vs. 192 mu mol L-1 (5% dialysis-dependent), but were comparable regarding disease severity. SMR at 1 and 5 years were 2.1 (95% CI: 0.43-6.09) and 1.6 (95% CI: 0.6-3.2) in the recent cohort and 5.2 (95% CI: 1.07-15.14) and 2.5 (95% CI: 0.93-5.52) in the old cohort. Five-year survival was 87% and 81%. Serum creatinine, age, end-stage renal disease, diagnosis before 1997 and first relapse were independent predictors for death. Patient survival in WG and MPA analysed with SMR may be better than previously believed. Severe renal disease and disease relapse were the major predictors of reduced survival.
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| 6. |
- Salomonsson, S., et al.
(författare)
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A Population-based Investigation of the Autoantibody Profile in Mothers of Children with Atrioventricular Block
- 2011
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Ingår i: Scandinavian Journal of Immunology. - Oxford : Blackwell Publishing. - 0300-9475 .- 1365-3083. ; 74:5, s. 511-517
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.
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| 7. |
- Sjöwall, Christopher, et al.
(författare)
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Abnormal Antinuclear Antibody Titers Are Less Common Than Generally Assumed in Established Cases of Systemic Lupus Erythematosus.
- 2008
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 35, s. 1994-2000
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate antinuclear antibody (ANA) tests in established cases of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) by indirect immunofluorescence microscopy (F-ANA) and enzyme-immunoassays detecting antinucleosomal antibodies (ANSA-EIA). METHODS: Sera from 50 patients with SLE and 65 patients with RA were analyzed regarding abnormal concentrations of F-ANA (serum dilution >/= 1:200 = 95th percentile among 300 healthy blood donors). The sera were also analyzed with 2 commercial ANSA-EIA kits. RESULTS: An abnormal F-ANA titer occurred in 76% of the SLE sera compared to 23% in RA, and was not related to present use of antirheumatic drugs. At dilution 1:50, 84% of the SLE sera were F-ANA-positive compared to 20% of healthy women. Forty percent and 56%, respectively, of the SLE sera tested positive in the 2 ANSA-EIA kits. By the most sensitive assay, 96% of the ANSA-positive SLE sera produced a homogenous (chromosomal) F-ANA staining pattern compared to 18% of the ANSA-negative SLE sera. Ten of the 15 F-ANA-positive RA sera (63%) generated homogenous F-ANA staining and 13 (20%) tested positive in the most sensitive ANSA-EIA, but with no correlation to the F-ANA staining pattern. CONCLUSION: The sensitivity of F-ANA at an abnormal titer was surprisingly low (76%) in established cases of SLE. ANSA occurred in 56% of the SLE sera, but also in a fair number (20%) of RA sera. Practically all ANSA-positive SLE sera were identified by chromosomal F-ANA staining. We conclude that the antigen-specific antinucleosomal EIA does not have high enough diagnostic specificity to justify use of this analysis for routine diagnostic purposes.
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| 8. |
- Sjöwall, Christoffer, et al.
(författare)
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C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis
- 2013
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 46:3, s. 205-214
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Tidskriftsartikel (refereegranskat)abstract
- The pattern recognition molecules C-reactive protein (CRP) and C1q are of big interest in relation to the pathogenesis of systemic lupus erythematosus (SLE). Circulating autoantibodies against CRP and C1q are frequently found in SLE patients with active disease, particularly in lupus nephritis (LN), and rising levels reportedly relate to disease activity and outcome. If CRP-, or dsDNA- and/or C1q-containing immune complexes (ICs) are pathogenic in LN, glomerular IgG-deposits would be expected to co-localize with these antigens. In search for proof of this concept, renal biospsies from patients with active LN (n = 5) were examined with high-resolution immunogold electron microscopy. Renal biopsies from patients with Henoch-Schonlein purpura, pauci-immune nephritis and renal cancer served as controls. IgG antibodies against CRP, C1q and nucleosomes were analyzed in pre-post flare sera. We could demonstrate that CRP, C1q, C3c and dsDNA were co-localized with IgG in electron dense deposits in the glomerular basement membrane/subendothelial space in all of the 5 LN patients. Deposits of IgG, CRP, complement and dsDNA were 10-fold higher in LN compared to controls. All SLE patients had circulating anti-nucleosome antibodies; 4/5 had serum antibodies against CRP, dsDNA, and C1q at biopsy/flare. Despite a limited number of cases, the results support the notion of a pathogenic role not only for anti-dsDNA antibodies, but also for anti-CRP and anti-C1q in LN. The glomerular ICs may have been generated by deposition of circulating ICs or by in situ IC formation.
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| 10. |
- Sjöwall, Christoffer, et al.
(författare)
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Reduced anti-TNFα autoantibody levels coincide with flare in systemic lupus erythematosus
- 2004
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 22:4, s. 315-323
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Tidskriftsartikel (refereegranskat)abstract
- Deviating cytokine patterns, as a consequence of aberrant immunoregulation, is implicated to be of aetiopathogenetic importance in systemic lupus erythematosus (SLE). To evaluate the possibility of anti-cytokine autoantibody-mediated cytokine regulation/dysregulation, IgG class autoantibodies against cytokines (IL-1β, IL-6, IL-10, TNFα and TGFβ1) were analysed by enzyme-linked immunosorbent assay (ELISA) in serial serum samples from clinically well-characterized SLE patients and in normal human sera (NHS). Anti-TNFα autoantibody levels were lower in patients with active disease compared to inactive disease (P<0.001) as well as to NHS (P<0.001). The anti-TNFα antibody levels correlated inversely to the SLE disease activity index (SLEDAI) (r2=0.07, P<0.01), whereas anti-TGFβ antibodies were raised in SLE and correlated positively to levels of complement factor C1q (r2=0.08, P<0.005). Generally raised anti-cytokine antibody levels and correlations to disease activity measures were found in one individual. Inverse correlations were found comparing SLEDAI scores and autoantibodies to TNFα (r2=0.92) and IL-6 (r2=0.86) and positive correlations were found between levels of anti-TNFα and C1q (r2=0.86) and C3 (r2=0.90). We show, for the first time, a coincidence between reduced anti-TNFα autoantibody levels and disease exacerbation in SLE, which is of interest regarding aetiopathogenesis and disease control.
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