Is the humoral immunity dispensable for the pathogenesis of psoriasis?
Is the humoral immunity dispensable for the pathogenesis of psoriasis?
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DOI：
10.1111/jdv.15101
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发表时间：
2019-01-01
影响因子：
9.2
通讯作者：
Garzorz-Stark, N.
中科院分区：
文献类型：
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作者：
Thomas, J.;Kuepper, M.;Garzorz-Stark, N.
背景 T 细胞亚群失衡是银屑病疾病特异性炎症的标志。然而，B 细胞与牛皮癣的相关性仍缺乏研究。目的分析B细胞和免疫球蛋白在银屑病特异性免疫学中的作用。方法 我们对未经治疗的银屑病患者 (n = 37) 的 B 细胞亚群和免疫球蛋白水平进行了表征，并将其与健康对照 (n = 20) 以及接受疾病控制全身治疗的银屑病患者 (n = 28) 进行比较。根据基于表面标记 CD24、CD38 和 CD138 的流式细胞门控策略对 B 细胞亚群进行分析。此外，免疫荧光染色用于检测银屑病皮肤中的 IgA。结果我们发现初治银屑病患者血清中 IgA 水平显着升高，与疾病评分相关。然而，IgA 仅在皮肤切片的真皮血管中观察到。关于 B 细胞亚群，我们仅发现初治银屑病患者中 CD138(+) 浆细胞与 IgA 水平和疾病评分呈中度正相关。为了证实我们的假设，即牛皮癣可以在缺乏功能性体液免疫的情况下发生，我们调查了一名同时患有牛皮癣和以缺乏 B 细胞和免疫球蛋白为特征的遗传性常见变异免疫缺陷 (CVID) 的患者。我们检测到 13 个已描述的 CVID 基因中的 3 个存在变异，以及 TNFRSF13B 受体配体中迄今为止未描述的变异，导致 B 细胞成熟和抗体产生受到干扰。然而，该患者在临床表现、组织学或 T 细胞浸润方面表现出典型的银屑病。最后，在一组接受全身治疗的银屑病患者中，IgA 水平既没有下降，浆细胞也没有与 IgA 水平和疾病评分相关。结论 B 细胞改变可能是银屑病的一个附带现象，其中 T 细胞明显优于 B 细胞亚群的变化。
Background Imbalances of T-cell subsets are hallmarks of disease-specific inflammation in psoriasis. However, the relevance of B cells for psoriasis remains poorly investigated. Objective To analyse the role of B cells and immunoglobulins for the disease-specific immunology of psoriasis. Methods We characterized B-cell subsets and immunoglobulin levels in untreated psoriasis patients (n = 37) and compared them to healthy controls (n = 20) as well as to psoriasis patients under disease-controlling systemic treatment (n = 28). B-cell subsets were analysed following the flow cytometric gating strategy based on the surface markers CD24, CD38 and CD138. Moreover, immunofluorescence stainings were used to detect IgA in psoriatic skin. Results We found significantly increased levels of IgA in the serum of treatment-naive psoriasis patients correlating with disease score. However, IgA was only observed in dermal vessels of skin sections. Concerning B-cell subsets, we only found a moderately positive correlation of CD138(+) plasma cells with IgA levels and disease score in treatment-naive psoriasis patients. Confirming our hypothesis that psoriasis can develop in the absence of functional humoral immunity, we investigated a patient who suffered concomitantly from both psoriasis and a hereditary common variable immune defect (CVID) characterized by a lack of B cells and immunoglobulins. We detected variants in three of the 13 described genes of CVID and a so far undescribed variant in the ligand of the TNFRSF13B receptor leading to disturbed B-cell maturation and antibody production. However, this patient showed typical psoriasis regarding clinical presentation, histology or T-cell infiltrate. Finally, in a group of psoriasis patients under systemic treatment, neither did IgA levels drop nor did plasma cells correlate with IgA levels and disease score. Conclusion B-cell alterations might rather be an epiphenomenal finding in psoriasis with a clear dominance of T cells over shifts in B-cell subsets.