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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.

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