Dirks Johannes, Fischer Jonas, Haase Gabriele, Holl-Wieden Annette, Hofmann Christine, Girschick Hermann, Morbach Henner
Pediatric Immunology, University Children's Hospital, Würzburg, Germany.
Pediatric Rheumatology and Osteology, University Children's Hospital, Würzburg, Germany.
Front Pediatr. 2021 Apr 16;9:635815. doi: 10.3389/fped.2021.635815. eCollection 2021.
Juvenile idiopathic arthritis (JIA) encompasses a heterogeneous group of diseases. The appearance of antinuclear antibodies (ANAs) in almost half of the patients suggests B cell dysregulation as a distinct pathomechanism in these patients. Additionally, ANAs were considered potential biomarkers encompassing a clinically homogenous subgroup of JIA patients. However, in ANA+ JIA patients, the site of dysregulated B cell activation as well as the B cell subsets involved in this process is still unknown. Hence, in this cross-sectional study, we aimed in an explorative approach at characterizing potential divergences in B cell differentiation in ANA+ JIA patients by assessing the distribution of peripheral blood (PB) and synovial fluid (SF) B cell subpopulations using flow cytometry. The frequency of transitional as well as switched-memory B cells was higher in PB of JIA patients than in healthy controls. There were no differences in the distribution of B cell subsets between ANA- and ANA+ patients in PB. However, the composition of SF B cells was different between ANA- and ANA+ patients with increased frequencies of CD21CD27IgM "double negative" (DN) B cells in the latter. DN B cells might be a characteristic subset expanding in the joints of ANA+ JIA patients and are potentially involved in the antinuclear immune response in these patients. The results of our explorative study might foster further research dissecting the pathogenesis of ANA+ JIA patients.
幼年特发性关节炎（JIA）涵盖一组异质性疾病。近半数患者出现抗核抗体（ANA），提示B细胞失调是这些患者独特的发病机制。此外，ANA被认为是JIA患者临床同质亚组的潜在生物标志物。然而，在ANA阳性的JIA患者中，B细胞活化失调的部位以及参与这一过程的B细胞亚群仍不清楚。因此，在这项横断面研究中，我们旨在通过流式细胞术评估外周血（PB）和滑液（SF）B细胞亚群的分布，以探索性方法表征ANA阳性JIA患者B细胞分化的潜在差异。JIA患者外周血中过渡性和转换记忆B细胞的频率高于健康对照。外周血中ANA阴性和ANA阳性患者的B细胞亚群分布没有差异。然而，ANA阴性和ANA阳性患者的滑液B细胞组成不同，后者中CD21CD27IgM“双阴性”（DN）B细胞频率增加。DN B细胞可能是ANA阳性JIA患者关节中扩增的特征性亚群，并可能参与这些患者的抗核免疫反应。我们的探索性研究结果可能会促进对ANA阳性JIA患者发病机制的进一步研究。
