Pireddu Marta Paola, Rizzo Giulia, Congiu Fabio, Chessa Elisabetta, Pitzalis Maristella, Ragusa Elena, Floris Alberto, Deidda Francesca, Congia Mattia, Naitza Micaela Rita, Angioni Maria Maddalena, Cucca Francesco, Cauli Alberto, Piga Matteo
Rheumatology, Department of Medical Sciences and Public Health, University of Cagliari, Italy.
Rheumatology Unit, AOU Cagliari, Italy.
J Autoimmun. 2025 Jul;155:103455. doi: 10.1016/j.jaut.2025.103455. Epub 2025 Jun 29.
To examine whether SLE patients carrying the TNFSF13B variant (BAFF-var) differ in the risk of overall and renal flares and the benefits from belimumab.
This retrospective study analyzed data from a monocentric cohort of Sardinian SLE patients between January 2006 and December 2022. We recorded demographic, clinical, serological, and treatment variables. A flare was defined as a new SLE manifestation or worsening of an existing one that required a change in therapy. Renal flares, categorized as nephritic or nephrotic, were recorded. Soluble B-cell activating factor (sBAFF) levels were evaluated in patients naïve to any treatment. We used Kaplan-Meier curves, Cox regression, and Poisson regression to investigate the association between BAFF-var and flares.
Among 233 screened patients, 194 (89.2 % female, 61.3 % BAFF-var carriers) were included. The mean age was 41.1 (±14.8) years, and the mean number of follow-up visits was 17 (±8). sBAFF levels increased according to BAFF-var genotype (p < 0.001). BAFF-var was significantly associated with an increased risk of flares (HR 1.5 per copy variant; 95 %CI 1.2-2.0; p = 0.002), and the frequency of flares (IRR 1.3 per copy variant; 95 %CI 1.1-1.6; p = 0.009). In 38 biopsy-confirmed lupus nephritis patients, the BAFF-var was associated with a higher risk of renal flare (HR 9.3; 95 %CI 1.7-49.5; p = 0.008). In 35 relapsing-remitting patients, belimumab reduced both the risk and frequency of flares, with higher effectiveness in patients carrying the BAFF-var (HR 0.12; 95 %CI 0.02-0.58; p = 0.009).
Pending further validation, BAFF-var may serve as a predictive and prognostic biomarker for personalized treatment in SLE.
研究携带TNFSF13B基因变异（BAFF变异）的系统性红斑狼疮（SLE）患者在总体病情发作和肾脏病情发作风险方面是否存在差异，以及在接受贝利尤单抗治疗时是否能从中获益。
这项回顾性研究分析了2006年1月至2022年12月期间来自撒丁岛SLE患者单中心队列的数据。我们记录了人口统计学、临床、血清学和治疗变量。病情发作被定义为需要改变治疗方案的新出现的SLE表现或现有症状的恶化。记录分类为肾炎性或肾病性的肾脏病情发作情况。对未接受过任何治疗的患者评估可溶性B细胞活化因子（sBAFF）水平。我们使用Kaplan-Meier曲线、Cox回归和Poisson回归来研究BAFF变异与病情发作之间的关联。
在233名筛查患者中，纳入了194名（89.2%为女性，61.3%为BAFF变异携带者）。平均年龄为41.1（±14.8）岁，平均随访次数为17（±8）次。sBAFF水平根据BAFF变异基因型升高（p<0.001）。BAFF变异与病情发作风险增加显著相关（每拷贝变异的风险比为1.5；95%置信区间1.2 - 2.0；p = 0.002），以及病情发作频率增加（每拷贝变异的发病率比为1.3；95%置信区间1.1 - 1.6；p = 0.009）。在38例经活检确诊的狼疮性肾炎患者中，BAFF变异与肾脏病情发作风险较高相关（风险比为9.3；95%置信区间1.7 - 49.5；p = 0.008）。在35例复发缓解型患者中，贝利尤单抗降低了病情发作的风险和频率，在携带BAFF变异的患者中疗效更高（风险比为0.12；95%置信区间0.02 - 0.58；p = 0.009）。
在进一步验证之前，BAFF变异可能作为SLE个性化治疗的预测和预后生物标志物。
