特异性抗体分泌型腺体细胞能预测干燥综合症患者的临床表现
发表者：杨麟
日期：2015-02-27
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摘要: 目的：原发性干燥综合征(SS)的血清学标志物为抗SSA和SSB抗体。原发性干燥综合征炎症部位的腺体起源的B细胞的分子特征已被叙述过。但腺体抗体分泌细胞和血清的抗体特异性之间的关系还未被充分评估。我们使用重组单克隆抗体技术在研究腺体抗体分泌细胞的特异性，评估他们的分子特征，并且鉴定IgG抗体的特异性。
方法：腺体抗体分泌细胞能够分泌人类抗体。测序分析重链和轻链和免疫球蛋白亚类。酶联免疫吸附试验、间接免疫荧光、酶免疫分析法和35 s标记蛋白免疫沉淀反应分析是用来确定抗体的特异性。
结果：从一个干燥综合症患者和一个干燥和重叠系统性红斑狼疮患者的泪腺活检显示腺体起源抗体分泌细胞与血清自身一致的特异性。腺体起源抗体分泌细胞的重链和轻链广泛存在突变，提示可能由抗原刺激。重要的是,我们制造了第一个来自于泪腺的人IgG。
结论：在干燥综合症患者中,唾液腺是产生除SSA和SSB之外抗体的主要部位。腺体抗体的产生强烈提示了我们所研究的2例患者血清学的体液免疫的不同。
附原文：Objective The serologic hallmark of primary Sjögren's syndrome (SS) is the presence of IgG antibodies specific for Ro (SSA) and La (SSB). The molecular characteristics of gland-derived B cells at the site of primary SS inflammation have been described previously; however, parallels between glandular antibody-secreting cells (ASCs) and serologic antibody specificities have not been evaluated. We used recombinant monoclonal antibody (mAb) technology to study the specificities of salivary gland (SG)–derived ASCs, evaluate their molecular characteristics, and identify IgG antibody specificity.Methods Human antibodies were generated from glandular IgG ASCs. Heavy chain and light chain use and immunoglobulin subclass were analyzed by sequencing. Enzyme-linked immunosorbent assay, indirect immunofluorescence, enzyme immunoassay, and 35S-labeled protein immunoprecipitation analysis were used to determine antibody specificity. Results: Evaluation of single ASCs in SG biopsy specimens from a patient with primary SS and a patient with SS and overlapping systemic lupus erythematosus revealed significant concordance between serum autoantibody and glandular ASC specificities. Gland-derived ASC heavy chains and light chains were extensively somatically hypermutated, which is indicative of antigen-driven responses. Specifically, we produced the first fully human mAb derived from SGs. Conclusion: In patients with SS, the SGs are a site for the production of antibodies that extend beyond the canonical Ro and/or La SS specificities. Glandular antibody production strongly reflected the serologic humoral response in the 2 patients whom we studied.
引自：Maier-Moore JS, Koelsch KA, Smith K, Lessard CJ, Radfar L, Lewis D, Kurien BT, Wolska N, Deshmukh U, Rasmussen A, Sivils KL, James JA, Farris AD, Scofield RH. Antibody-Secreting Cell Specificity in Labial Salivary Glands Reflects the Clinical Presentation and Serology in Patients With Sjögren's Syndrome. Arthritis Rheumatol. 2014 Dec;66(12):3445-56. doi:10.1002/art.38872. （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）
方法：腺体抗体分泌细胞能够分泌人类抗体。测序分析重链和轻链和免疫球蛋白亚类。酶联免疫吸附试验、间接免疫荧光、酶免疫分析法和35 s标记蛋白免疫沉淀反应分析是用来确定抗体的特异性。
结果：从一个干燥综合症患者和一个干燥和重叠系统性红斑狼疮患者的泪腺活检显示腺体起源抗体分泌细胞与血清自身一致的特异性。腺体起源抗体分泌细胞的重链和轻链广泛存在突变，提示可能由抗原刺激。重要的是,我们制造了第一个来自于泪腺的人IgG。
结论：在干燥综合症患者中,唾液腺是产生除SSA和SSB之外抗体的主要部位。腺体抗体的产生强烈提示了我们所研究的2例患者血清学的体液免疫的不同。
附原文：Objective The serologic hallmark of primary Sjögren's syndrome (SS) is the presence of IgG antibodies specific for Ro (SSA) and La (SSB). The molecular characteristics of gland-derived B cells at the site of primary SS inflammation have been described previously; however, parallels between glandular antibody-secreting cells (ASCs) and serologic antibody specificities have not been evaluated. We used recombinant monoclonal antibody (mAb) technology to study the specificities of salivary gland (SG)–derived ASCs, evaluate their molecular characteristics, and identify IgG antibody specificity.Methods Human antibodies were generated from glandular IgG ASCs. Heavy chain and light chain use and immunoglobulin subclass were analyzed by sequencing. Enzyme-linked immunosorbent assay, indirect immunofluorescence, enzyme immunoassay, and 35S-labeled protein immunoprecipitation analysis were used to determine antibody specificity. Results: Evaluation of single ASCs in SG biopsy specimens from a patient with primary SS and a patient with SS and overlapping systemic lupus erythematosus revealed significant concordance between serum autoantibody and glandular ASC specificities. Gland-derived ASC heavy chains and light chains were extensively somatically hypermutated, which is indicative of antigen-driven responses. Specifically, we produced the first fully human mAb derived from SGs. Conclusion: In patients with SS, the SGs are a site for the production of antibodies that extend beyond the canonical Ro and/or La SS specificities. Glandular antibody production strongly reflected the serologic humoral response in the 2 patients whom we studied.
引自：Maier-Moore JS, Koelsch KA, Smith K, Lessard CJ, Radfar L, Lewis D, Kurien BT, Wolska N, Deshmukh U, Rasmussen A, Sivils KL, James JA, Farris AD, Scofield RH. Antibody-Secreting Cell Specificity in Labial Salivary Glands Reflects the Clinical Presentation and Serology in Patients With Sjögren's Syndrome. Arthritis Rheumatol. 2014 Dec;66(12):3445-56. doi:10.1002/art.38872. （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）