In Situ Humoral Immunity to Vimentin in HLA-DRB1*03(+) Patients With Pulmonary Sarcoidosis.
In Situ Humoral Immunity to Vimentin in HLA-DRB1*03(+) Patients With Pulmonary Sarcoidosis.
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DOI：
10.3389/fimmu.2018.01516
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发表时间：
2018
影响因子：
7.3
通讯作者：
Grunewald J
中科院分区：
文献类型：
--
作者：
Kinloch AJ;Kaiser Y;Wolfgeher D;Ai J;Eklund A;Clark MR;Grunewald J
波形蛋白作为T细胞自身抗原与肺结节病有关，特别是在HLA-DRB 1 *03、Vα2.3/Vβ22 T细胞受体（TCR）和洛夫格伦综合征的背景下。由于波形蛋白是B细胞介导的自身免疫中的已知抗原靶点，我们研究了肺结节病中的原位体液抗波形蛋白应答及其与HLA-DRB 1 *03的关系。通过多色共聚焦显微镜分析结节病和健康对照（HC）肺活检的B细胞、T细胞、增殖和波形蛋白，并与扁桃体切除术组织进行比较。对48名结节病患者和15名健康志愿者的支气管肺泡灌洗液（BALF）和血清进行HLA-DRB 1 *03分型，并通过ELISA滴定全长波形蛋白抗体、波形蛋白截短抗体和总IgG和伊加。通过质谱法测定BALF中细胞外波形蛋白的存在，并通过流式细胞术测量T细胞群。结节病肺样本，特别是来自HLA-DRB 1 *03+患者的样本，含有富含波形蛋白的三级淋巴样结构，相应的BALF高度富集IgG和伊加抗波形蛋白抗体（AVA）滴度。此外，结节病患者BALF AVA浓度（表示为任意单位/mg总免疫球蛋白同种型）与表达Vα2.3/Vβ22 TCR的CD 4 + T细胞百分比相关。BALF抗体对波形蛋白N-末端的反应性在HC中最突出，而对C-末端（VimC-末端）的反应性在结节病肺中富集。具体而言，HLA-DRB 1 *03+患者BALF中抗VimC-term抗体的浓度高于HC和HLA-DRB 1 *03−患者的BALF。与肺作为AVA产生的部位一致，BALF中AVA的浓度显著高于匹配的血清样品。总体而言，BALF和血清AVA浓度之间的相关性较差。总之，这些研究揭示了HLA-DRB 1 *03+结节病患者中T细胞和B细胞对波形蛋白的原位识别的存在，与对波形蛋白C末端的选择性体液免疫应答相关。
Vimentin has been implicated in pulmonary sarcoidosis as a T-cell autoantigen, particularly in the context of HLA-DRB1*03, the Vα2.3/Vβ22 T-cell receptor (TCR), and Löfgren’s syndrome. As vimentin is a known antigenic target in B-cell-mediated autoimmunity, we investigated in situ humoral anti-vimentin responses in pulmonary sarcoidosis and their relationship with HLA-DRB1*03. Sarcoid and healthy control (HC) lung biopsies were analyzed by multi-color confocal microscopy for B-cells, T-cells, proliferation, and vimentin, and compared to tonsillectomy tissue. Bronchoalveolar lavage fluid (BALF) and serum from 48 sarcoidosis patients and 15 healthy volunteers were typed for HLA-DRB1*03 and titrated for antibodies to full-length vimentin, vimentin truncations, and total IgG and IgA by ELISA. Presence of extracellular vimentin in BALF was determined by mass spectrometry and T-cell populations measured by flow cytometry. Sarcoid lung samples, especially from HLA-DRB1*03+ patients, contained vimentin-rich tertiary lymphoid structures and corresponding BALF was highly enriched for both IgG and IgA anti-vimentin antibody (AVA) titers. Furthermore, sarcoidosis patient BALF AVA concentrations (expressed as arbitrary units per milligram of total immunoglobulin isotype) correlated with the percentage of CD4+ T-cells expressing the Vα2.3/Vβ22 TCR. BALF antibody reactivity to the vimentin N-terminus was most prominent in HCs, whereas reactivity to the C-terminus (VimC-term) was enriched in the sarcoid lung. Specifically, HLA-DRB1*03+ patient BALF contained higher concentrations of anti-VimC-term antibodies than BALF from both HCs and HLA-DRB1*03− patients. Consistent with the lung as a site of AVA production, the concentration of AVAs in BALF was dramatically higher than in matched serum samples. Overall, there was a poor correlation between BALF and serum AVA concentrations. Together, these studies reveal the presence of linked in situ recognition of vimentin by both T- and B-cells in HLA-DRB1*03+ sarcoidosis patients, associated with a selective humoral immune response to the vimentin C-terminus.
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Kveim试剂的蛋白质组学分析鉴定了结节病中细胞免疫的靶标。
影响因子：
3.7
作者：
Eberhardt C;Thillai M;Parker R;Siddiqui N;Potiphar L;Goldin R;Timms JF;Wells AU;Kon OM;Wickremasinghe M;Mitchell D;Weeks ME;Lalvani A
通讯作者：
Lalvani A
影响因子：
21.3
作者：
Mor-Vaknin, N;Punturieri, A;Markovitz, DM
通讯作者：
Markovitz, DM
影响因子：
13.3
作者：
Kinloch, Andrew J.;Chang, Anthony;Clark, Marcus R.
通讯作者：
Clark, Marcus R.
影响因子：
24.3
作者：
Planck, A;Eklund, A;Grunewald, J
通讯作者：
Grunewald, J
DOI：
10.1111/j.1600-6143.2012.04053.x
发表时间：
2012-08
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Porcheray F;DeVito J;Helou Y;Dargon I;Fraser JW;Nobecourt P;Ferdman J;Germana S;Girouard TC;Kawai T;Saidman SL;Wong W;Colvin RB;Leguern C;Zorn E
通讯作者：
Zorn E