Induction of alternative splicing of HLA‐B27 by bacterial invasion

Abstract

Objective. Alternative splicing of certain class I major histocompatibility complex pre-messenger RNA (pre-mRNA) is known to lead to generation of a cell-free soluble protein analog. This study was undertaken to examine whether this process occurs with HLA-B27, whether the process is modified by arthritis-causing bacteria, and whether the assembly of the soluble molecules follows the same pathway as the integral parent molecules.Methods. Alternative splicing of pre-mRNA was analyzed by reverse transcriptase-polymerase chain reaction, and assembly of soluble HLA-B27 by immunoprecipitation followed by sodium dodecyl sulfatepolyacrylamide gel electrophoresis and autoradiography.Results. There was alternative splicing of the pre-mRNA of HLA-B27. The process could be amplified by invasion with Salmonella or Yersinia bacteria. The soluble HLA-B27 was assembled in a pathway similar to that of the parent molecule.Conclusion. The association between arthritiscausing bacteria and HLA-B27 positive cells is a complex event. Soluble HLA-B27 is a potential key player.Two factors contribute to reactive arthritis. First, the arthritis is induced by infection with invasive bacteria

HLA-B27-Associated Reactive Arthritis: Pathogenetic and Clinical Considerations

“…Interestingly, S. enterica serovar Typhimurium and Y. enterocolitica also induce alternative splicing of the premRNA of HLA-B27 with removal of the fifth exon. Because this fifth exon encodes the transmembrane domain, cell-free soluble HLA-B27 is generated (75).…”

The Peptide Repertoires of HLA-B27 Subtypes Differentially Associated to Spondyloarthropathy (B*2704 and B*2706) Differ by Specific Changes at Three Anchor Positions

“…It has also been suggested that misfolding of HLA-B27 heavy chains, perhaps exacerbated by infection or other environmental factors, might lead to endoplasmic reticulum stress responses and inflammation independent of antigen presentation (8,9). Other effects of HLA-B27 on modulating bacteria-host interactions have also been proposed (10,11). Supportive evidence for the arthritogenic peptide hypothesis comes from population studies showing differential association of some HLA-B27 subtypes with AS.…”

HLA-B27 Expression Does Not Modulate IntracellularChlamydia trachomatisInfection of Cell Lines

“…Indeed, an alteration in the splicing of B27 mRNA leading to the production of soluble HLA-B27 has been detected after infection of cell lines with Yersinia and Salmonella spp. (9). …”