B cell epitopes of the heterogeneous nuclear ribonucleoprotein A2: identification of a new specific antibody marker for active lupus disease

Abstract

Peptide p155-175 encompasses a disease-specific immunodominant epitope of hnRNP-A2. Since antibodies to p155-175 correlate with disease activity and nephritis, they may be useful as markers for active SLE.

Nucleic acid-associated autoantigens: Pathogenic involvement and therapeutic potential

“…The B-cell epitope hnRNP-A2 155e175 appears to be specific for SLE and is significantly associated with disease activity, skin rash, renal and mucocutaneous manifestations, and arthritis in lupus [218]. In contrast to SLE, anti-RA33 Abs in RA may be associated with a more benign disease [222] However, B and T cell reactivity to some linear sequences seems to be linked to active disease and erosion in arthritis ( [218] and unpublished results from our lab). Abs against hnRNP-A1 cross-react with the HTLV-1-tax protein, thus suggesting molecular mimicry between the two proteins.…”

“…A conformational A2-epitope recognized by Ab from MCTD patients comprises both RRMs and appears different from another one recognized by Abs from SLE and RA patients [217]. Short linear epitopes appear to be selectively recognized by autoAbs from SLE patients and recognition of one particular epitope was found to correlate with lupus disease activity [218]. The epitopes involved in HAM/TSP are encompassed in hnRNP-A1 191e202 and 293e304, and HTLV-1-tax 346e353 [219].…”

Nucleic acid-stimulated antigen-presenting cells trigger T cells to induce disease in a rat transfer model of inflammatory arthritis

“…HnRNP-A2/B1 is targeted by autoantibodies and T cells of patients with RA, SLE, and mixed connective tissue disease [9e13]. Interestingly however, B cell epitope recognition was found to differ among the diseases [14,15] and remarkable differences were observed between RA and SLE patients with respect to T cell reactivity [10,11].…”

The antigen specificity of the rheumatoid arthritis-associated ACPA directed to citrullinated fibrin is very closely restricted

“…For example, on two 15-mer peptides derived from the sequence of the centromere-associated protein CENP-A targeted by a large majority of sera containing anticentromere autoantibodies, it was shown that all sera recognise two immunologically related motifs harbouring a consensus sequence. Other examples are given by autoantibodies to Ro60 found to recognise a unique immunodominant 12-mer epitope in almost all the positive sera [36] and by autoantibodies to the heterogeneous nuclear ribonucleoprotein A2 (hnRNP-A2), mainly directed to 4 peptides of which one is immunodominant (aa 155e175) [37]. All together, data in the literature show that the immunodominance of a restricted number of epitopes is a general feature of the B immune response.…”