Proteomic analysis in idiopathic pulmonary fibrosis with presence of anti-modified protein antibodies

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Introduction We have discovered that certain antibodies towards anti-modified proteins (AMPA) related to rheumatoid arthritis (RA) are also present in patients with idiopathic pulmonary fibrosis (IPF). Whether levels of proteins are different based on presence of AMPA is not known. Aim To explore the protein profile in peripheral blood of patients based on the presence of AMPA. Methods Serum from 30 IPF patients was tested for antibodies using a custom-made microarray immunochip. A panel of 92 inflammation and oncology related proteins were examined with proximity extension assay. Differences in protein levels between AMPA groups were evaluated with Welch’s t-test. Results Increased levels of antibodies against modified proteins were observed in 40% (n=12) of IPF patients. Overall, 84 out of 92 measured proteins such as IL6 and TNF-alpha were similar in AMPA positive and AMPA negative patients. AMPA positive patients demonstrated decreased levels of CD94 (mean ± SD normalized protein expression (NPX): 6.84 ± 0.55 vs 6.30 ± 0.44 (p=0.006)) and GZMH (5.42 ± 0.73 vs 4.82 ± 0.53, p=0.02) compared to AMPA negative patients. Conclusion The differentiated immune responses in IPF may further be reflected by differences in protein expression. Overall, the levels of proteins were similar in AMPA positive and negative IPF patients. Further studies are necessary to investigate the significance of autoimmunity and how immunological pathways are differentially activated in IPF.

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