Comment on: Persistence of circulating T-follicular helper cells after rituximab is associated with relapse of IgG4-related disease
Comment on: Persistence of circulating T-follicular helper cells after rituximab is associated with relapse of IgG4-related disease
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评论：利妥昔单抗后循环滤泡辅助性 T 细胞的持续存在与 IgG4 相关疾病的复发相关
DOI：
10.1093/rheumatology/keab687
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发表时间：
2021
期刊：
影响因子：
5.5
通讯作者：
Kaneko Yuko
中科院分区：
文献类型：
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作者：
Akiyama Mitsuhiro;Kaneko Yuko
亲爱的编辑，我们怀着极大的兴趣阅读了曼库索等人的文章[1]。他们报告说，即使在临床改善和利妥昔单抗清除B细胞后，来自IgG4相关疾病(IgG4-RD)患者的循环滤泡辅助T(TFH)细胞数量仍保持不变。他们还提出，持续的TFH可能与疾病未来的复发有关。与他们的观察一致，我们之前报道过，在糖皮质激素治疗后，IgG4-RD患者循环中Tfh细胞数量的增加并未得到纠正[2-4]。此外，我们发现在疾病复发时TFH细胞重新激活[2]。这些结果提示糖皮质激素或B细胞靶向治疗如利妥昔单抗不足以抑制IgG4-RD中TFH细胞的数量和/或其致病功能。考虑到疾病的频繁复发和糖皮质激素的毒性作用，显然需要新的治疗靶点。我们希望提供我们的观察，滤泡树突状细胞(FDCs)可能是在疾病发病机制中发挥作用的罪魁祸首细胞类型之一。在受影响的IgG4-RD组织中，众所周知，异位生发中心，即所谓的第三淋巴器官出现，并在TFH细胞的帮助下参与产生IgG4的浆细胞分化[5]。一般来说，FDC通过分泌CXCL13来启动生发中心的形成，从而吸引CXCR5+Tfh和B细胞。与Mancuso等人的报告相似[1]，我们先前报道，通过全面的蛋白质组分析，血清CXCL13水平在IgG4-RD患者中升高[7]。我们发现CD21+FDCs位于IgG4-RD异位生发中心的光区(图1)。值得注意的是，最近的一项研究表明，FDCs不仅通过分泌CXCL13来吸引Tfh和B细胞，启动生发中心的形成，而且还通过表达HLA-DR参与Tfh和B细胞的抗原依赖性选择过程[6]。事实上，IgG4-RD受累部位的FDCs呈网状，使它们能够与TfH和B细胞亲密接触(图1)。此外，FDDC直接激活生发中心的TFH细胞[6]。我们注意到位于异位生发外的T细胞
DEAR EDITOR, We read the article by Mancuso et al.[1] with great interest. They reported that the number of circulating follicular helper T (Tfh) cells from patients with IgG4-related disease (IgG4-RD) remained unchanged even after clinical improvement and B cell depletion by rituximab. They also suggested that persisting Tfh might be associated with future relapse of the disease. In line with their observations, we previously reported that the increased number of circulating Tfh cells was not corrected after clinical improvement by glucocorticoid in patients with IgG4-RD [2–4]. Furthermore, we found reactivation of Tfh cells at relapse of the disease [2]. These results suggest that glucocorticoid or B cell targeting therapy such as rituximab is insufficient to suppress the number of Tfh cells and/or their pathogenic function in IgG4-RD. Considering the frequent relapse of the disease and the toxic effects of glucocorticoids, new therapeutic targets are obviously desired in this disease.We would like to provide our observation that follicular dendritic cells (FDCs) might be one of the culprit cell types that plays a role in the disease pathogenesis. In the affected tissues of IgG4-RD, it is well known that the ectopic germinal centres, socalled tertiary lymphoid organs, emerge and are involved in IgG4-producing plasma cell differentiation with the help of Tfh cells [5]. In general, FDC attracts CXCR5+ Tfh and B cells by secreting CXCL13 to initiate germinal centre formation [6]. Similar to the report by Mancuso et al.[1], we previously reported that serum CXCL13 levels were elevated in IgG4-RD by comprehensive proteomic analysis [7]. We found that CD21+ FDCs reside within the light zone of ectopic germinal centres of IgG4-RD (Fig. 1). Of note, a recent study has revealed that FDCs not only initiate germinal centre formation by attracting Tfh and B cells through CXCL13 secretion, but are also involved in the antigen-dependent selection process of Tfh and B cells through HLA-DR expression [6]. In fact, the shape of FDCs in the affected site of IgG4-RD is like ‘meshwork’, enabling their intimate contact with both Tfh and B cells (Fig. 1). In addition, FDCs directly activate Tfh cells in the germinal centres [6]. We note that T cells residing outside of the ectopic germinal