AUF1, the regulator of tumor necrosis factor α messenger RNA decay, is targeted by autoantibodies of patients with systemic rheumatic diseases

Abstract

Objective. To investigate which members of the heterogeneous nuclear RNP (hnRNP) family are targeted by autoantibodies from patients with systemic rheumatic diseases.Methods. Using a semipurified preparation of natural hnRNP proteins, 365 sera from patients with rheumatic diseases and control subjects were screened by immunoblotting for the presence of autoantibodies. Bacterially expressed recombinant hnRNP D (AUF1) proteins were used for confirming the data obtained. Binding of RNA and autoantibody to AUF1 was investigated by gel retardation assays. Expression of AUF1 in cultivated cells and synovial tissue was analyzed by indirect immunofluorescence and immunohistochemistry.Results. Autoantibodies to AUF1 proteins were detected in 33% of patients with systemic lupus erythematosus, 20% of patients with rheumatoid arthritis, 17% of patients with mixed connective tissue disease, and <10% of patients with other rheumatic disorders. Epitope mapping studies showed the autoantibodies to be directed to conformational epitopes in the N-terminal RNA-binding part of AUF1. However, autoantibody binding did not interfere with RNA binding as assessed by gel-shift assays. Immunohistochemical studies revealed AUF1 to be expressed in the cytoplasm of RA synovial tissue as compared with nuclear staining in osteoarthritis and normal synovium, particularly in macrophages of the lining layer and in fibroblasts of the sublining areas.Conclusion. These data identify AUF1 proteins as novel autoantigens in SLE and related autoimmune disorders. Because AUF1 proteins are major components of messenger RNA stability complexes, our findings suggest that these complexes form a novel macromolecular target structure for autoantibodies in rheumatic autoimmune diseases.

Heterogeneous Nuclear Ribonucleoprotein H1, a Novel Nuclear Autoantigen

“…Recently, hnRNP L was identified as a novel autoantigen associated with anti-hnRNP A/B antibodies (29 ). hnRNP D (AUF1) was described as an autoantibody target in patients with systemic rheumatic diseases (mainly SLE and RA) (35 ).…”

Nucleic acid-associated autoantigens: Pathogenic involvement and therapeutic potential

“…AutoAbs to the hnRNP-C proteins were occasionally found in the sera of patients with SSc, psoriatic arthritis, and myositis [211]. AutoAbs to hnRNP-D have been reported to occur in 33% of SLE, 20% of RA, and 17% of MCTD patients [212]. HnRNP-I is an autoantigen in SSc [213].…”

Association of the RAVER2 gene with increased susceptibility for ulcerative colitis

“…A number of hnRNP proteins have been described as autoantigens in several ADs such as, rheumatoid arthritis, SLE, and mixed connective tissue disease [38]. Antibodies to hnRNP A1 and HnRNP D (AUF1) have been reported in SLE [39,40]. Antibodies to hnRNP G have been described in dogs with SLE [41].…”