Anti-citrullinated heat shock protein 90 antibodies identified in bronchoalveolar lavage fluid are a marker of lung-specific immune responses.
Anti-citrullinated heat shock protein 90 antibodies identified in bronchoalveolar lavage fluid are a marker of lung-specific immune responses.
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DOI：
10.1016/j.clim.2014.08.004
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Ascherman DP
中科院分区：
文献类型：
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作者：
Harlow L;Gochuico BR;Rosas IO;Doyle TJ;Osorio JC;Travers TS;Camacho CC;Oddis CV;Ascherman DP
先前的工作已经证明了血清抗瓜氨酸化HSP 90抗体与类风湿性关节炎相关间质性肺病（RA-ILD）之间的相关性。为了进一步研究这种潜在的致病关系，我们使用基于ELISA的技术来评估不同阶段RA-ILD患者支气管肺泡灌洗液（BALF）中的抗瓜氨酸化HSP 90抗体谱。9/21份RA来源的BALF标本显示出靶向瓜氨酸化HSP 90蛋白/肽的IgG和/或伊加抗体，突出显示了IPF患者（0/5）或健康对照受试者（0/5）中未发生的疾病特异性应答（偏好RA-ILD）。BALF和匹配的血清标本之间的抗体谱的比较揭示了各种识别模式，有利于抗瓜氨酸化HSP 90抗体在肺微环境中的主要生产，进一步支持这种抗体特异性和实质性肺病之间的联系。同样重要的是，BALF和血清之间抗瓜氨酸化HSP 90谱的定性和定量差异表明肺在RA/RA-ILD的免疫库形成中起直接作用。
Previous work has demonstrated a correlation between serum anti-citrullinated HSP90 antibodies and rheumatoid arthritis-associated interstitial lung disease (RA-ILD). To further investigate this potential pathogenic relationship, we used ELISA-based techniques to assess anti-citrullinated HSP90 antibody profiles in bronchoalveolar lavage fluid (BALF) of patients with different stages of RA-ILD. 9/21 RA-derived BALF specimens demonstrated IgG and/or IgA antibodies targeting citrullinated HSP90 proteins/peptides, highlighting disease specific responses (with a predilection for RA-ILD) that did not occur in IPF patients (0/5) or healthy control subjects (0/5). Comparison of antibody profiles between BALF and matching serum specimens revealed various recognition patterns favoring predominant production of anti-citrullinated HSP90 antibodies within the lung microenvironment—further supporting the connection between this antibody specificity and parenchymal lung disease. Equally important, qualitative as well as quantitative differences in anti-citrullinated HSP90 profiles between BALF and serum indicate that the lung plays a direct role in shaping the immune repertoire of RA/RA-ILD.