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American Thoracic Society, American Journal of Respiratory and Critical Care Medicine, 5(191), p. 574-583, 2015

DOI: 10.1164/rccm.201407-1341oc

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Proteomic Profiling Reveals Autoimmune Targets in Sarcoidosis

This paper is available in a repository.
This paper is available in a repository.

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Data provided by SHERPA/RoMEO

Abstract

Rationale: There is a need to further characterize the antibody repertoire in relation to sarcoidosis and potentially related auto-antigens. Objectives: We investigated bronchoalveolar lavage (BAL) and serum samples from sarcoidosis patients and healthy as well as diseased controls to discover sarcoidosis-associated autoantigens. Methods: Antigen microarrays built on 3,072 protein fragments were utilized to screen for IgG reactivity in 73 BAL samples from sarcoidosis, asthma and healthy subjects. A set of 131 targets were selected for subsequent verification on suspension bead arrays using 272 additional BAL samples as well as 141 paired sera. Reactivity to four antigens was furthermore analyzed in 22 unprocessed BAL samples from fibrosis patients and 269 plasma samples from patients diagnosed with myositis. Measurements and main results: Reactivity towards zinc finger protein 688 (ZNF688) and mitochondrial ribosomal protein L43 (MRPL43) were discovered with higher frequencies in sarcoidosis patients, for MRPL43 especially in patients with non-Löfgren's syndrome. Increased reactivity towards nuclear receptor coactivator 2 (NCOA2) was also observed in patients with non-Löfgren's syndrome as compared to Löfgrens patients. The antigen representing ADP-ribosylation factor GTPase activating protein 1 (ARFGAP1), revealed high reactivity frequency in all sample groups but with significantly higher level of IgG reactivities in sarcoidosis patients. Conclusions: Autoantigen reactivity was present in the majority of BAL and serum samples analyzed and the results revealed high inter-individual heterogeneity with the majority of reactivities observed in single individuals only. Four proteins are here proposed as sarcoidosis associated autoimmune targets and of interest for further validation in independent cohorts.