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类风湿关节炎中的异常 B 细胞激活和 B 细胞亚群:通过临床活动、自身抗体血清阳性和治疗进行分析。

Aberrant B-cell activation and B-cell subpopulations in rheumatoid arthritis: analysis by clinical activity, autoantibody seropositivity, and treatment.

机构信息

Centro Universitario de Ciencias de la Salud, Doctorado en Ciencias Biomédicas, Universidad de Guadalajara, Jalisco, Mexico.

Centro Universitario de Ciencias de la Salud, Instituto de Investigación en Ciencias Biomédicas (IICB), Universidad de Guadalajara, Jalisco, Mexico.

出版信息

Clin Exp Immunol. 2023 Dec 13;214(3):314-327. doi: 10.1093/cei/uxad076.

DOI:10.1093/cei/uxad076
PMID:37464892
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10719220/
Abstract

Few studies analyze the role of B-cell subpopulations in rheumatoid arthritis (RA) pathophysiology. Therefore, this study aimed to analyze the differences in B-cell subpopulations and B-cell activation according to disease activity, RA subtype, and absence of disease-modifying antirheumatic drugs (DMARDs) therapy. These subgroups were compared with control subjects (CS). One hundred and thirty-nine subjects were included, of which 114 were RA patients, and 25 were controls. Patients were divided into 99 with seropositive RA, 6 with seronegative RA, and 9 without DMARDs. The patients with seropositive RA were subclassified based on the DAS28 index. A seven-color multicolor flow cytometry panel was used to identify B-cell immunophenotypes and cell activation markers. There were no changes in total B-cell frequencies between RA patients and controls. However, a lower frequency of memory B cells and pre-plasmablasts was observed in seropositive RA compared to controls (P < 0.0001; P = 0.0043, respectively). In contrast, a higher frequency of mature B cells was observed in RA than in controls (P = 0.0002). Among patients with RA, those with moderate activity had a higher percentage of B cells (P = 0.0021). The CD69+ marker was increased (P < 0.0001) in RA compared to controls, while the CD40+ frequency was decreased in patients (P < 0.0001). Transitional, naïve, and double-negative B-cell subpopulations were higher in seronegative RA than in seropositive (P < 0.01). In conclusion, in seropositive and seronegative RA patients, there are alterations in B-cell activation and B-cell subpopulations, independently of clinical activity and DMARDs therapy.

摘要

目前很少有研究分析 B 细胞亚群在类风湿关节炎(RA)发病机制中的作用。因此,本研究旨在根据疾病活动度、RA 亚型和是否使用疾病修饰抗风湿药物(DMARDs)治疗来分析 B 细胞亚群和 B 细胞活化的差异。这些亚组与对照受试者(CS)进行比较。共纳入 139 例受试者,其中 114 例为 RA 患者,25 例为对照。患者分为血清阳性 RA 患者 99 例、血清阴性 RA 患者 6 例和未使用 DMARDs 患者 9 例。血清阳性 RA 患者根据 DAS28 指数进行亚组分类。采用七色多色流式细胞术面板来鉴定 B 细胞免疫表型和细胞活化标志物。RA 患者和对照之间总 B 细胞频率没有变化。然而,与对照相比,血清阳性 RA 患者的记忆 B 细胞和前浆母细胞频率较低(P < 0.0001;P = 0.0043)。相反,RA 患者的成熟 B 细胞频率高于对照(P = 0.0002)。在 RA 患者中,中度活动患者的 B 细胞百分比更高(P = 0.0021)。与对照相比,RA 患者的 CD69+标志物增加(P < 0.0001),而患者的 CD40+频率降低(P < 0.0001)。与血清阳性 RA 患者相比,血清阴性 RA 患者的过渡性、幼稚性和双阴性 B 细胞亚群更高(P < 0.01)。总之,在血清阳性和血清阴性 RA 患者中,B 细胞活化和 B 细胞亚群存在改变,与临床活动度和 DMARDs 治疗无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/719d/10719220/09458c5795e3/uxad076_fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/719d/10719220/09458c5795e3/uxad076_fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/719d/10719220/09458c5795e3/uxad076_fig8.jpg

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