Proteomic profiling reveals autoimmune targets in sarcoidosis

Am J Respir Crit Care Med. 2015 Mar 1;191(5):574-83. doi: 10.1164/rccm.201407-1341OC.

Abstract

Rationale: There is a need to further characterize the antibody repertoire in relation to sarcoidosis and potentially related autoantigens.

Objectives: We investigated bronchoalveolar lavage (BAL) and serum samples from patients with sarcoidosis and healthy and diseased control subjects to discover sarcoidosis-associated autoantigens.

Methods: Antigen microarrays built on 3,072 protein fragments were used to screen for IgG reactivity in 73 BAL samples from subjects with sarcoidosis, subjects with asthma, and healthy subjects. A set of 131 targets were selected for subsequent verification on suspension bead arrays using 272 additional BAL samples and 141 paired sera. Reactivity to four antigens was furthermore analyzed in 22 unprocessed BAL samples from patients with fibrosis and 269 plasma samples from patients diagnosed with myositis.

Measurements and main results: Reactivity toward zinc finger protein 688 and mitochondrial ribosomal protein L43 were discovered with higher frequencies in patients with sarcoidosis, for mitochondrial ribosomal protein L43 especially in patients with non-Löfgren syndrome. Increased reactivity toward nuclear receptor coactivator 2 was also observed in patients with non-Löfgren syndrome as compared with patients with Löfgren syndrome. The antigen representing adenosine diphosphate-ribosylation factor GTPase activating protein 1 revealed high reactivity frequency in all sample groups but with significantly higher level of IgG reactivities in patients with sarcoidosis.

Conclusions: Autoantigen reactivity was present in most BAL and serum samples analyzed, and the results revealed high interindividual heterogeneity, with most of the 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.

Keywords: Löfgren syndrome; affinity proteomics; autoimmunity; bronchoalveolar lavage; sarcoidosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autoantigens / analysis*
  • Biomarkers / analysis
  • Bronchoalveolar Lavage Fluid / chemistry
  • Carrier Proteins / analysis
  • Carrier Proteins / blood
  • Carrier Proteins / immunology
  • Female
  • GTPase-Activating Proteins / analysis
  • GTPase-Activating Proteins / immunology
  • High-Throughput Screening Assays
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mitochondrial Proteins / analysis
  • Mitochondrial Proteins / blood
  • Mitochondrial Proteins / immunology
  • Nuclear Receptor Coactivator 2 / analysis
  • Nuclear Receptor Coactivator 2 / immunology
  • Protein Array Analysis
  • Proteomics
  • Ribosomal Proteins / analysis
  • Ribosomal Proteins / blood
  • Ribosomal Proteins / immunology
  • Sarcoidosis, Pulmonary / blood
  • Sarcoidosis, Pulmonary / diagnosis*
  • Sarcoidosis, Pulmonary / immunology*
  • Young Adult
  • Zinc Fingers / immunology

Substances

  • ARFGAP1 protein, human
  • Autoantigens
  • Biomarkers
  • Carrier Proteins
  • GTPase-Activating Proteins
  • L43 protein, human
  • Mitochondrial Proteins
  • NCOA2 protein, human
  • Nuclear Receptor Coactivator 2
  • Ribosomal Proteins
  • ZNF688 protein, human