Autoreactive T cells to citrullinated HSP90 are associated with interstitial lung disease in rheumatoid arthritis.
AIM
Previous analysis of comparative anti-citrullinated heat shock protein 90 (citHSP90) antibody profiles between bronchoalveolar lavage fluid and serum indicates that the lung plays a direct role in shaping the immune repertoire of rheumatoid arthritis-associated interstitial lung disease (RA-ILD).


METHODS
To address the contribution of citHSP90β-specific T cells in this process, we evaluated in vitro cytokine responses to citHSP90β in RA patients with different stages of ILD as well as in controls with non-RA connective tissue disease-associated ILD (CTD-ILD). Cultures derived from whole blood were individually stimulated with HSP90β, citHSP90β, citrullinated BSA, or no antigen. The concentrations of 13 cytokines and chemokines in the plasma supernatant were then measured using Luminex xMAP technology.


RESULTS
CitHSP90β induced significantly higher levels of interferon-γ (IFN-γ) levels in RA-ILD (interstitial lung abnormalities = 2 + 3) groups compared to the RA-no ILD group (P = 0.01), but did not stimulate the production of other cytokines (P > 0.05). Furthermore, citHSP90β did not stimulate the production of IFN-γ or other cytokines in those individuals with non-RA CTD-ILD.


CONCLUSION
Overall, the production of IFN-γ by T cells stimulated with citHSP90β demonstrates a bias toward TH1 immune responses that are likely involved in the pathogenesis of RA-ILD.
['Chen|Juan|J|http://orcid.org/0000-0002-3328-9627', 'Song|Shuli|S|', 'Liu|Yongliang|Y|', 'Liu|Dehao|D|', 'Lin|Yihua|Y|', 'Ge|Shengxiang|S|', 'Ascherman|Dana P|DP|']
D000328:Adult D000075422:Anti-Citrullinated Protein Antibodies D001172:Arthritis, Rheumatoid D015415:Biomarkers D001992:Bronchoalveolar Lavage Fluid D016022:Case-Control Studies D002478:Cells, Cultured D005260:Female D018841:HSP90 Heat-Shock Proteins D006801:Humans D007371:Interferon-gamma D017563:Lung Diseases, Interstitial D008213:Lymphocyte Activation D008297:Male D008875:Middle Aged D013601:T-Lymphocytes D018417:Th1 Cells
T cell citrullination interstitial lung disease rheumatoid arthritis heat shock protein 90 interferon-gamma