Association between peripheral activated naive and double negative 2 B-cell subsets and clinical parameters in lupus nephritis patients.

IF 4.1 4区 医学 Q2 IMMUNOLOGY Scandinavian Journal of Immunology Pub Date : 2025-01-01 Epub Date: 2024-11-26 DOI:10.1111/sji.13427
Kittikorn Wangriatisak, Charlotte de Vries, Ravi Kumar Sharma, Wenqi Huang, Caroline Grönwall, Prapaporn Pisitkun, Iva Gunnarsson, Vivianne Malmström, Patchanee Chootong, Francesca Faustini
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Abstract

Altered composition of B-cell compartments is a known feature in patients with systemic lupus erythematosus (SLE). However, deep characterisation of B-cell subsets and their relation to clinical manifestations and disease activity in patients is limited. In this study, we analysed peripheral B-cell subsets phenotype in SLE (n = 35) and healthy controls (HCs, n = 15) by spectral flow cytometry. Disease activity was stratified as inactive (SLEDAI-2 K score 0, n = 2), mild (SLEDAI-2 K score 1-5, n = 12), moderate (SLEDAI-2 K score 6-10, n = 6) or high (SLEDAI-2 K > 10, n = 15). An elevated proportion of activated naive (aNAV), double negative 2 (DN2) and plasmablasts (PB) was observed in patients with high disease activity, compared to other groups of patients and HCs. An upregulation of BTLA was found on both aNAV and DN2 and shifted to lower levels with increasing disease activity. In lupus nephritis (LN) patients (n = 21), aNAV B-cells were especially expanded and positively correlated with DN2 (r = 0.5, p = 0.019) and PB (r = 0.43, p = 0.048). Also, correlation was observed between DN2 and PB (r = 0.6, p = 0.003). Moreover, aNAV frequencies positively correlated with SLEDAI-2 K score, and negatively with the complement fractions C3 and C4. Further, aNAV, DN2 and PB were more expanded in association with positive anti-dsDNA antibodies, rather than other antibody specificities (anti-Sm). These data suggest roles of extrafollicular B cells as key players in disease development of LN. Their association with presence of anti-dsDNA antibodies may indicate their value as candidate biomarkers of kidney involvement in SLE.

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狼疮性肾炎患者外周活化的天真和双阴性 2 型 B 细胞亚群与临床指标之间的关系。
B细胞组成的改变是系统性红斑狼疮(SLE)患者的一个已知特征。然而,对B细胞亚群及其与患者临床表现和疾病活动的关系的深入研究还很有限。在这项研究中,我们通过光谱流式细胞术分析了系统性红斑狼疮患者(35 人)和健康对照组(15 人)的外周 B 细胞亚群表型。疾病活动度分为非活动(SLEDAI-2 K 评分 0,n = 2)、轻度(SLEDAI-2 K 评分 1-5,n = 12)、中度(SLEDAI-2 K 评分 6-10,n = 6)或高度(SLEDAI-2 K > 10,n = 15)。与其他组患者和 HCs 相比,在疾病活动度高的患者中观察到活化的幼稚细胞(aNAV)、双阴性 2 型细胞(DN2)和浆细胞(PB)比例升高。在 aNAV 和 DN2 上都发现了 BTLA 的上调,并随着疾病活动性的增加而转为较低水平。在狼疮性肾炎(LN)患者(n = 21)中,aNAV B 细胞尤其增大,并与 DN2(r = 0.5,p = 0.019)和 PB(r = 0.43,p = 0.048)呈正相关。DN2 和 PB 之间也存在相关性(r = 0.6,p = 0.003)。此外,aNAV 频率与 SLEDAI-2 K 评分呈正相关,与补体分数 C3 和 C4 呈负相关。此外,aNAV、DN2 和 PB 与抗dsDNA 抗体阳性相关,而不是与其他抗体特异性(抗-Sm)相关。这些数据表明,滤泡外 B 细胞是 LN 疾病发展的关键因素。它们与抗dsDNA抗体的存在有关,这可能表明它们是系统性红斑狼疮肾脏受累的候选生物标志物。
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来源期刊
CiteScore
7.70
自引率
5.40%
发文量
109
审稿时长
1 months
期刊介绍: This peer-reviewed international journal publishes original articles and reviews on all aspects of basic, translational and clinical immunology. The journal aims to provide high quality service to authors, and high quality articles for readers. The journal accepts for publication material from investigators all over the world, which makes a significant contribution to basic, translational and clinical immunology.
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