Proteomic profiling reveals autoimmune targets in sarcoidosis

Area of Science:

• Immunology
• Autoimmunity
• Pulmonary Medicine

Background:

• Sarcoidosis autoimmunity requires further characterization of antibody repertoires.
• Identification of sarcoidosis-associated autoantigens is crucial for understanding disease mechanisms.

Purpose of the Study:

• To discover novel autoantigens associated with sarcoidosis.
• To investigate antibody reactivity in bronchoalveolar lavage (BAL) and serum samples from sarcoidosis patients and controls.

Main Methods:

• Utilized antigen microarrays with 3,072 protein fragments to screen IgG reactivity in BAL samples.
• Verified reactivity on suspension bead arrays using additional BAL samples and paired sera.
• Analyzed reactivity to specific antigens in BAL samples from patients with fibrosis and plasma samples from patients with myositis.

Main Results:

• Identified increased reactivity to zinc finger protein 688 and mitochondrial ribosomal protein L43 in sarcoidosis patients.
• Observed elevated reactivity to nuclear receptor coactivator 2 in patients with non-Löfgren syndrome.
• Found significantly higher IgG reactivity to adenosine diphosphate-ribosylation factor GTPase activating protein 1 in sarcoidosis patients.

Conclusions:

• Autoantigen reactivity is prevalent in sarcoidosis BAL and serum samples, exhibiting significant interindividual heterogeneity.
• Four proteins are proposed as potential sarcoidosis-associated autoimmune targets.
• Further validation of these proposed targets in independent cohorts is warranted.