Immune complexes containing serum B-cell activating factor and immunoglobulin G correlate with disease activity in systemic lupus erythematosus

Friebus‐Kardash, Justa; Branco, Leonore; Ribi, Camillo; Chizzolini, Carlo; Huynh‐Do, Uyen; Dubler, Denise; Roux‐Lombard, Pascale; Dolff, Sebastian; Kribben, Andreas; Eisenberger, Ute; Trendelenburg, Marten

doi:10.1093/ndt/gfx220

Cited by 14 publications

(12 citation statements)

References 37 publications

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“…In support of this theory, abnormal serum levels of BAFF have been detected among SLE patients [10, 11]. Our previous study and numerous other reports found an association between BAFF serum concentrations, disease activity, and the occurrence of lupus nephritis [11–14]. In line with these observations, clinical trials demonstrated the effectiveness of belimumab in reducing the number of autoantibodies and reducing disease activity among SLE patients [8, 15, 16].…”

Section: Introductionsupporting

confidence: 64%

“…BAFF was considered to contribute to the pathogenesis of SLE by enhancing the proliferation and survival of autoreactive B cells, thereby leading to overproduction of diverse autoantibodies [9, 10]. In support of this theory, abnormal serum levels of BAFF have been detected among SLE patients [10, 11]. Our previous study and numerous other reports found an association between BAFF serum concentrations, disease activity, and the occurrence of lupus nephritis [11–14].…”

Section: Introductionmentioning

confidence: 74%

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Susceptibility of BAFF-var allele carriers to severe SLE with occurrence of lupus nephritis

et al. 2019

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Background: Dysregulation of the B-cell activating factor (BAFF) system is involved in the pathogenesis of systemic lupus erythematosus (SLE). Increased serum concentrations of BAFF are related to lupus nephritis and disease activity among SLE patients. Recently, a variant of the BAFF-encoding gene, BAFF-var, was identified to be associated with autoimmune diseases, in particular SLE, and to promote the production of soluble BAFF. The present study aimed to assess the prevalence of BAFF-var in a cohort of 195 SLE patients and to analyze the association of the BAFF-var genotype (TNSF13B) with various manifestations of SLE. Methods: A cohort of 195 SLE patients from Central Europe, including 153 patients from the Swiss SLE Cohort Study and 42 patients from the University Hospital Essen, Germany, underwent genotyping for detection of BAFFvar allele. Results: Of the 195 patients, 18 (9.2%) tested positive for BAFF-var variant according to the minor allele frequency of 4.6%. The presence of BAFF-var was associated with the occurrence of lupus nephritis (p = 0.038) (p = 0.03 and p = 0.003). Among various organ manifestations of SLE, the presence of BAFF-var was associated with the occurrence of lupus nephritis (p = 0.038; odds ratio [OR], 2.4; 95% confidence interval [CI], 0.89-6.34) and renal activity markers such as proteinuria and hematuria (p = 0.03; OR, 2.4; 95% CI, 0.9-6.4 for proteinuria; p = 0.003; OR, 3.9; 95% CI, 1.43-10.76 for hematuria). SLE patients carrying the BAFF-var allele exhibited increased disease activity at study entry, as determined by the physician's global assessment (PGA: p = 0.002; OR, 4.8; 95% CI, 1.54-14.93) and the SLE Disease Activity Index (p = 0.012; OR, 3.5; 95% CI, 1.12-11.18). Consistent with that, the percentage of patients treated with immunosuppressive agents at study entry was higher among those carrying the BAFF-var allele than among those tested negative for BAFF-var (p = 0.006; OR, 3.7; 95% CI, 1.27-10.84). Conclusions: Our results indicate an association between the BAFF-var genotype and increased severity of SLE. Determining the BAFF-var status of SLE patients may improve the risk stratification of patients for whom the development of lupus nephritis is more likely and thus may be helpful in the follow-up care and treatment of SLE patients.

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Section: Introductionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 74%

Susceptibility of BAFF-var allele carriers to severe SLE with occurrence of lupus nephritis

et al. 2019

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“…These findings are likely attributable to the fact that the presence of the BAFF-var allele led to an increased production of soluble BAFF, thereby resulting in sustained high levels of BAFF. Consistently, several studies have found that elevated BAFF levels are linked to lupus nephritis and exacerbation of SLE [11][12][13][14]. However, serum concentrations of BAFF are modulated by additional regulatory factors (e.g., current B-cell number, type of immunosuppressive treatment etc.)…”

Section: Discussionmentioning

confidence: 76%

Susceptibility of BAFF-var allele carriers to severe SLE with occurrence of lupus nephritis

Friebus‐Kardash

Trendelenburg

Eisenberger

et al. 2019

Preprint

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Background: Dysregulation of the B-cell activating factor (BAFF) system is involved in the pathogenesis of systemic lupus erythematosus (SLE). Increased serum concentrations of BAFF are related to lupus nephritis and disease activity among SLE patients. Recently, a variant of the BAFF-encoding gene, BAFF-var, was identified to be associated with autoimmune diseases, in particular SLE, and to promote the production of soluble BAFF. The present study aimed to assess the prevalence of BAFF-var in a cohort of 195 SLE patients and to analyze the association of the BAFF-var genotype (TNSF13B) with various manifestations of SLE. Methods: A cohort of 195 SLE patients from Central Europe, including 153 patients from the Swiss SLE Cohort Study and 42 patients from the University Hospital Essen, Germany, underwent genotyping for detection of BAFF-var allele. Results: Of the 195 patients, 18 (9.2%) tested positive for BAFF-var variant according to the minor allele frequency of 4.6%. The presence of BAFF-var was associated with the occurrence of lupus nephritis (p=0.038) (p=0.03 and p=0.003). Among various organ manifestations of SLE, the presence of BAFF-var was associated with the occurrence of lupus nephritis (p=0.038; odds ratio [OR], 2.4; 95% confidence interval [CI], 0.89-6.34) and renal activity markers such as proteinuria and hematuria (p=0.03; OR, 2.4; 95% CI, 0.9-6.4 for proteinuria; p=0.003; OR, 3.9; 95% CI, 1.43-10.76 for hematuria). SLE patients carrying the BAFF-var allele exhibited increased disease activity at study entry, as determined by the physician's global assessment (PGA: p=0.002; OR, 4.8; 95% CI, 1.54-14.93) and the SLE Disease Activity Index (p=0.012; OR, 3.5; 95% CI, 1.12-11.18). Consistent with that, the percentage of patients treated with immunosuppressive agents at study entry was higher among those carrying the BAFF-var allele than among those tested negative for BAFF-var (p=0.006; OR, 3.7; 95% CI, 1.27-10.84). Conclusions: Our results indicate an association between the BAFF-var genotype and increased severity of SLE. Determining the BAFF-var status of SLE patients may improve the risk stratification of patients for whom the development of lupus nephritis is more likely and thus may be helpful in the follow-up care and treatment of SLE patients.

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“…Raised anti-BAFF autoantibody levels were found to correlate with disease activity in pediatric SLE patients [55]. In contrast, a Swiss study of adult SLE patients did not demonstrate an increase in anti-BAFF autoantibody levels or any association with SLE disease activity while serum BAFF-IgG complexes were associated with serological and clinical SLE disease activity [13]. We recently observed elevated levels of anti-BAFF antibodies in the majority of our multi-ethnic Asian SLE patients, which correlated negatively with clinical disease activity, levels of anti-dsDNA antibodies, and serum BAFF, suggesting that they may be immunomodulatory in nature and may serve as a tool in monitoring disease progression [54].…”

Section: Anti-baff Autoantibodies In Slementioning

confidence: 85%

“…B-cell activating factor (BAFF), also known as BLyS, a member of the TNF superfamily of cytokines, contributes to SLE disease pathogenesis through promoting the survival of autoreactive B-cells, allowing their escape from negative selection [12,13]. Raised titers of anti-dsDNA and anti-Sm antibodies, hypocomplementemia, and increased BAFF levels are an independent risk factor for SLE disease flares [7].…”

Section: Serum Ifn-regulated Chemokine Levels Correlate Best With Dismentioning

confidence: 99%

Anti-Cytokine Autoantibodies in Systemic Lupus Erythematosus

Howe

Leung

2019

Cells

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Cytokine dysregulation is characteristic of systemic lupus erythematosus (SLE), a systemic autoimmune disease of considerable heterogeneity. Insights gained about the cytokine dysregulation in SLE have the potential for identifying patient subsets before the onset of clinical disease and during established disease. Clustering patients by cytokine and disease activity subsets is more informative than isolated cytokine studies, as both pro inflammatory and immunoregulatory cytokines contribute to the cytokine dysregulated state in SLE. Endogenous anti-cytokine autoantibodies (ACAAs) may be involved in the regulation of cytokine biology by reducing excessive production or by prolonging their half-life in the circulation through the formation of cytokine-antibody immune complexes. Although endogenous ACAAs may have deleterious effects such as contributing to immunodeficiency states, their role in the pathophysiology of autoimmune conditions such as SLE has yet to be clearly elucidated. The aim of the present article is to provide a focused review of the current knowledge of ACAAs in SLE.

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Immune complexes containing serum B-cell activating factor and immunoglobulin G correlate with disease activity in systemic lupus erythematosus

Abstract: BAFF-IgG complexes strongly correlate with disease activity in SLE patients, suggesting a pathogenic role in SLE.

Cited by 14 publications

References 37 publications

Susceptibility of BAFF-var allele carriers to severe SLE with occurrence of lupus nephritis

Susceptibility of BAFF-var allele carriers to severe SLE with occurrence of lupus nephritis

Susceptibility of BAFF-var allele carriers to severe SLE with occurrence of lupus nephritis

Anti-Cytokine Autoantibodies in Systemic Lupus Erythematosus

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