Department of Rheumatology and Clinical Immunology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, XM, 361000, China; Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China; Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China.
School of Medicine, Xiamen University, Xiamen, XM, 361000, China.
Semin Arthritis Rheum. 2024 Oct;68:152488. doi: 10.1016/j.semarthrit.2024.152488. Epub 2024 Jun 15.
Primary Sjögren syndrome (pSjS) is one of the most prevalent systemic autoimmune diseases and characterized with hyperactivation of B cell and the abundant presence of autoantibodies in sera. The salivary gland epithelial cells (SGECs) release autoantigens to evoke autoimmunity through releasing elevated apoptosis or secreting autoantigen-containing exosomes, thus identifying autoantibodies directly to SGECs might provide insights into disease related biomarkers as well as further elucidating pathogenesis mechanisms. The present study was undertaken to identify autoantibodies to SGECs and to evaluate its clinical values in Chinese pSjS.
Cell-based indirect immunofluorescence and immunostaining, two-dimensional electrophoresis and liquid chromatograph-tandem mass spectrometry were conducted to identify the autoantibodies to human salivary gland cell line A253 in pSjS sera. Enzyme-linked immunosorbent assay (ELISA) was applied to identify autoantibody titer in pSjS cohort and healthy controls. The prevalence and clinical significance of the identified autoantibodies was further assessed in pSjS population.
Anti-calreticulin (CALR) antibody was identified as a new autoantibody directly to SGECs in sera from pSjS patients. Anti-CALR antibody were detected in 37 of 120 pSjS patients (30.83 %) and 1 of 54 healthy controls (1.85 %). It was found in 40.85 % pSjS with anti-SSA positive, 53.85 % with anti-SSB positive, and 14.7 % in sero-negative pSjS. Anti-CALR antibody was associated with clinical manifestations including weight loss(p = 0.045), vasculitis (p = 0.031), and laboratory parameters including erythrocyte sedimentation rate (ESR) (r = 0.056, p = 0.021), Krebs von den Lungen-6 (KL-6) (r = 0.121, p = 0.035), IgG (r = 0.097, p < 0.001), IgG2 (r = 0.142, p = 0.022), IgG3 (r = 0.287, p < 0.001), fibrinogen (r = 0.084, p = 0.016), D-Dimer (r = 0.086, p = 0.012) and fibrinogen degradation production (r = 0.150, p = 0.002). The expression of CALR in salivary glands was related to lymphocytes infiltration into salivary glands in pSjS patients (r = 0.7076, p = 0.0034).
To our knowledge, this was the first study to investigate the prevalence and clinical significance of anti-CALR antibody in Chinses pSjS patients. The present study identified an autoimmune antibody, anti-CALR antibody, as a good autoimmune biomarker for sero-negative pSjS.
原发性干燥综合征（pSjS）是最常见的系统性自身免疫性疾病之一，其特征为 B 细胞过度激活和血清中大量存在自身抗体。唾液腺上皮细胞（SGECs）通过释放升高的凋亡或分泌含有自身抗原的外泌体来释放自身抗原，从而直接鉴定 SGECs 中的自身抗体可能为疾病相关生物标志物提供深入了解，并进一步阐明发病机制。本研究旨在鉴定 pSjS 血清中的 SGECs 自身抗体，并评估其在中国人中的临床价值。
通过细胞间接免疫荧光和免疫染色、二维电泳和液相色谱-串联质谱鉴定 pSjS 血清中抗人唾液腺细胞系 A253 的自身抗体。酶联免疫吸附试验（ELISA）用于鉴定 pSjS 队列和健康对照组中的自身抗体滴度。进一步评估在 pSjS 人群中鉴定出的自身抗体的患病率和临床意义。
鉴定出 calreticulin（CALR）抗体为 pSjS 患者血清中直接针对 SGECs 的新型自身抗体。在 120 例 pSjS 患者中的 37 例（30.83%）和 54 例健康对照中的 1 例（1.85%）中检测到抗-CALR 抗体。在 40.85%抗-SSA 阳性、53.85%抗-SSB 阳性和 14.7%血清阴性 pSjS 中发现了抗-CALR 抗体。抗-CALR 抗体与临床表现有关，包括体重减轻（p=0.045）、血管炎（p=0.031）和实验室参数，包括红细胞沉降率（ESR）（r=0.056，p=0.021）、Krebs von den Lungen-6（KL-6）（r=0.121，p=0.035）、IgG（r=0.097，p<0.001）、IgG2（r=0.142，p=0.022）、IgG3（r=0.287，p<0.001）、纤维蛋白原（r=0.084，p=0.016）、D-二聚体（r=0.086，p=0.012）和纤维蛋白原降解产物（r=0.150，p=0.002）。CALR 在唾液腺中的表达与 pSjS 患者唾液腺中淋巴细胞浸润有关（r=0.7076，p=0.0034）。
据我们所知，这是第一项研究抗-CALR 抗体在中国人 pSjS 患者中的患病率和临床意义的研究。本研究鉴定出一种自身抗体，抗-CALR 抗体，作为血清阴性 pSjS 的良好自身免疫生物标志物。
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