Toll-Like Receptor Homolog CD180 Expression Is Diminished on Natural Autoantibody-Producing B Cells of Patients with Autoimmune CNS Disorders. Toll-Like Receptor Homolog CD180 表达在自身免疫性中枢神经系统疾病患者的天然自身抗体产生 B 细胞中降低。
Toll-Like Receptor Homolog CD180 Expression Is Diminished on Natural Autoantibody-Producing B Cells of Patients with Autoimmune CNS Disorders.
机构信息
Department of Immunology and Biotechnology, Clinical Center, University of Pécs Medical School, H-7624 Pécs, Hungary.
Department of Neurology, Clinical Center, University of Pécs Medical School, H-7623 Pécs, Hungary.
出版信息
J Immunol Res. 2021 May 25;2021:9953317. doi: 10.1155/2021/9953317. eCollection 2021.
PURPOSE
Decreased expression of TLR homolog CD180 in peripheral blood B cells and its potential role in antibody production have been described in autoimmune diseases. Effectiveness of anti-CD20 therapy in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) strengthens the role of B cells in the pathogenesis. Therefore, we aimed to investigate the CD180 expression of peripheral blood B cell subsets in NMOSD and MS patients and analyze the levels of natural anti-citrate synthase (CS) IgG autoantibodies and IgG antibodies induced by bacterial infections reported to play a role in the pathogenesis of NMOSD or MS.
METHODS
We analyzed the distribution and CD180 expression of peripheral blood B cell subsets, defined by CD19/CD27/IgD staining, and measured anti-CS IgM/G natural autoantibody and antibacterial IgG serum levels in NMOSD, RRMS, and healthy controls (HC).
RESULTS
We found decreased naïve and increased memory B cells in NMOSD compared to MS. Among the investigated four B cell subsets, CD180 expression was exclusively decreased in CD19CD27IgD nonswitched (NS) memory B cells in both NMOSD and MS compared to HC. Furthermore, the anti-CS IgM natural autoantibody serum level was lower in both NMOSD and MS. In addition, we found a tendency of higher anti-CS IgG natural autoantibody levels only in anti-Chlamydia IgG antibody-positive NMOSD and MS patients.
CONCLUSIONS
Our results suggest that reduced CD180 expression of NS B cells could contribute to the deficient natural IgM autoantibody production in NMOSD and MS, whereas natural IgG autoantibody levels show an association with antibacterial antibodies.
目的
在自身免疫性疾病中已经描述了外周血 B 细胞中 TLR 同源物 CD180 的表达降低及其在抗体产生中的潜在作用。抗 CD20 治疗在视神经脊髓炎谱系障碍（NMOSD）和多发性硬化症（MS）中的有效性增强了 B 细胞在发病机制中的作用。因此，我们旨在研究 NMOSD 和 MS 患者外周血 B 细胞亚群的 CD180 表达，并分析报道在 NMOSD 或 MS 发病机制中起作用的天然抗柠檬酸合酶（CS）IgG 自身抗体和细菌感染诱导的 IgG 抗体的水平。
方法
我们分析了外周血 B 细胞亚群的分布和 CD180 表达，通过 CD19/CD27/IgD 染色定义，并测量了 NMOSD、RRMS 和健康对照组（HC）中的抗 CS IgM/G 天然自身抗体和抗细菌 IgG 血清水平。
结果
与 MS 相比，我们发现 NMOSD 中的幼稚 B 细胞减少，记忆 B 细胞增加。在所研究的四个 B 细胞亚群中，与 HC 相比，NMOSD 和 MS 中仅 CD19CD27IgD 未转换（NS）记忆 B 细胞中的 CD180 表达降低。此外，NMOSD 和 MS 患者的抗 CS IgM 天然自身抗体血清水平较低。此外，我们发现仅在抗衣原体 IgG 抗体阳性的 NMOSD 和 MS 患者中，抗 CS IgG 天然自身抗体水平有升高的趋势。
结论
我们的结果表明，NS B 细胞中 CD180 表达的降低可能导致 NMOSD 和 MS 中天然 IgM 自身抗体产生不足，而天然 IgG 自身抗体水平与抗细菌抗体有关。
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