Human major histocompatibility complex class I allele HLA-B27 is associated with a group of diseases called spondyloarthropathies. In reactive arthritis (ReA), the disease is triggered by certain infections, e.g. gastroenteritis caused by Salmonella. The host/microbe interaction is abnormal in susceptible individuals leading to inefficient elimination of arthritis-triggering bacteria, fragments of them, or both, after the initial infection. Using transfected human monocytic U937 cell lines, we demonstrate that the expression of the HLA-B27 antigen does not influence the uptake of S. enteritidis into U937 cells in vitro. Interestingly, HLA-B27 remarkably impairs the elimination of S. enteritidis within the HLA-B27 transfected U937 cells. The impaired elimination of ReA-triggering microbes by HLA-B27+ monocytes may offer an explanation for the persistence of ReA-triggering microbes in susceptible HLA-B27+ individuals. This modulation of the host/microbe interaction by HLA-B27 may have an important role in the pathogenesis of ReA.

These findings suggest that HLA-B27 enhances the invasion of Salmonella into intestinal epithelial cells. The interaction between bacteria and intestinal epithelial cells plays an important role during the early phases of ReA. HLA-B27-linked modulation of Salmonella invasion may lead to an increased load of Salmonella in intestinal tissue and thus increased susceptibility to reactive arthritis.

In Salmonella-triggered and Yersinia-triggered reactive arthritis (ReA), bacterial antigens have been demonstrated at the site of joint inflammation (1,2). In 2 previous studies by our group, Yersinia-specific plasmid (2) and chromosomal DNA (3) were not detected within the synovial fluid cells and synovial specimens from patients with ReA.In the present study, we attempted to amplify Salmonella DNA from the cells of synovial fluid and peripheral blood by applying the polymerase chain reaction (PCR) method. Initially, one set of Salmonellaspecific primers and a probe were used. The specimens were further analyzed by a hemi-nested PCR approach that uses Salmonella-specific primers and by a one-step PCR that uses primers specific for bacterial 23S ribosomal DNA (rDNA) sequences. The same specimens were studied by immunocytochemical staining to visualize Salmonella antigens. Gas chromatography-mass spectrometry (GC-MS) was used to detect bacteria-

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

Reactive arthritis is triggered by certain microbes that cause primary infections mainly on the gastrointestinal or urogenital mucosa. The disease is strongly associated with HLA-B27. Long persistence of causative microbes or their structures in the body has been thought to have an important role in the pathogenesis of reactive arthritis. This suggests that the elimination of the microbes causing reactive arthritis is ineffective or disturbed in HLA-B27-positive individuals developing this complication. We examined the role of the HLA-B27 antigen in microbe-host interaction in vitro by monitoring the invasion and intracellular survival of Salmonella enteritidis in mouse fibroblasts transfected with HLA-B27, HLA-B7, or ␤ 2-microglobulin only. S. enteritidis invaded into all the three transfectants with the same efficiency. However, at 6 and 10 days after incubation, there were more living intracellular Salmonella organisms in HLA-B27 transfectants than in the other transfected cell lines (P < 0.05), suggesting that the bactericidal effect is impaired in these cells. Impaired NO production in HLA-B27-transfected cells was indicated as a possible mechanism, since the amount of nitrite in the supernatants of the Salmonella-infected HLA-B27-transfected cells was smaller than that in the supernatants of the Salmonella-infected HLA-B7-or ␤ 2-microglobulin-transfected cells (P < 0.001). The inhibition of NO synthesis by N-monomethyl-L-arginine resulted in impaired elimination of Salmonella also in HLA-B7and ␤ 2-microglobulin-transfected cells. The inverse correlation between intracellular survival of Salmonella and the amount of nitrite detected in culture supernatants supports the hypothesis that the L-argininedependent NO pathway plays an important role in the murine fibroblast response against Salmonella. We suggest that a major histocompatibility complex class I antigen, HLA-B27, may contribute to the intracellular persistence of Salmonella by a mechanism which involves the NO pathway.