Multiple specificities of autoantibodies against hnRNP A/B proteins in systemic rheumatic diseases and hnRNP L as an associated novel autoantigen

Abstract

Spliceosomal small nuclear ribonucleoproteins (U-snRNPs) are frequent and specific targets of autoantibodies in systemic rheumatic diseases. The abundant, functionally related heterogeneous nuclear ribonucleoprotein complexes (hnRNPs) have later defined as a new target of autoantibodies, of which their immunochemical/immunogenic and pathogenic properties are still under investigation. Among hnRNP proteins, those belonging to the A/B type are considered as the major autoantigens targeted by antibodies in sera of patients suffering with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). By performing an extensive screening using rat liver 40S hnRNP antigenic material, we document here the existence of multiple specificities of anti-hnRNP A/B autoantibodies in sera of Greek patients suffering with a spectrum of systemic rheumatic diseases. This included patients with SLE, Sjogren's syndrome (SS), Scleroderma (SSc) and a specific group of patients mostly with undifferentiated disease (UD patients). In total, four distinct types of anti-hnRNP A/B autoantibodies have been recognized. The first two referred to the known anti-hnRNPA2(RA33) and anti-hnRNP A1; the latter appearing very rarely. The third was of the new type selectively reacting with hnRNP B2 and an hnRNP A3 variant, while the fourth was a rare case of anti-hnRNP B2 alone. In addition, a novel specificity of autoantibodies against hnRNP L protein was identified in association with anti-hnRNP A/B antibodies. The co-existence within a serum of autoantibodies having variable specificity for hnRNP A/B and L autoantigens was shown. Specific immunochemical features of the identified autoantibodies are presented and a possible mechanism of autoepitope spreading within protein components of hnRNP complexes is discussed.

Nucleic acid-associated autoantigens: Pathogenic involvement and therapeutic potential

“…HnRNP-I is an autoantigen in SSc [213]. Anti-HnRNP-L autoAbs are found in association with hnRNP-A/B autoAbs [214]. AutoAbs to hnRNP-A1/A2/B1 were detected in the cerebrospinal fluid (but not in the sera) of 91% of patients with MS [215], and hnRNP-A1 Abs are found in cerebrospinal fluid and in sera of patients with HAM/TSP [216] (Table 9).…”

Proteomic Evaluation to Identify Biomarkers for Carpal Tunnel Syndrome: A Comparative Serum Analysis

“…Subsequent identification and genecloning analysis showed that certain protein spots were in fact different isoforms generated from the same gene [39] with a total of 19 hnRNP genes identified. These proteins mainly function in the processing of precursor mRNA, but are also involved in telomeric DNA synthesis and apoptotic processes [40,41]. Through such functions, this family of proteins could potentially regulate tumorigenesis.…”

Heterogeneous Nuclear Ribonucleoprotein H1, a Novel Nuclear Autoantigen

“…Antibodies to hnRNP C1/C2 have been reported, but it is not known whether they are related to a specific disease (34 ). 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 ).…”

“…They mainly play a role in processing of precursor mRNA, but are also involved in telomeric DNA synthesis and cellular apoptotic processes (27)(28)(29). hnRNPs are composed of at least 1 RNA recognition motif, also termed the RNA-binding domain.…”