Background/Purpose:  The interrelationship between the gut microbiome and spondyloarthritis (SpA) has been highlighted by recent findings of (i) Subclinical bowel inflammation in SpA  (ii) Antimicrobial serology in AS which is comparable to inflammatory bowel disease (IBD) (iii) The association of HLA-B27 with chronicity in post-Salmonella reactive arthritis. This has raised the important unanswered question whether the HLA-B27 may influence disease susceptibility by an influencing the gut microbiome.

Methods: MHC-I transgenic mice were generated on a background of deleted endogenous MHC-I (DKO) and are designated by the transgenic allele: B27tg, B7tg, and A2tg, and compared with C57BL6 (WT). Mice were challenged with Salmonella typhimurium (5 x 10⁷ organisms) by gavage and followed to establish differential host responses.  Selected mice were euthanized at 24, 48 and 72 hr after infection. Colons were collected for H&E staining. Spleen, liver and mesenteric lymph nodes were dissected and cytokine gene expression determined by real-time PCR. At baseline and at selected time points, colonic contents were collected for analysis of the gut microbioata with primer sets specific for universal bacteria, g-proteobacteria, β-proteobacteria, bacteroidetes, firmicutes, and actinobacteria.

Results: Survival curves after oral Salmonella challenge indicated that the B27tg mouse demonstrated improved survival compared with B7tg and A2tg mice (Fig. 1).  Review of colon pathology, however, revealed no significant differences in the degree of colonic inflammation. Cytokine profiling in mesenteric lymph nodes at 72hr post-challenge showed that B7tg mice expressed less IFN-g and IL-10 and B27 expressed less Foxp3 than respective tg controls. Analysis of the gut microbioal composition at baseline prior to infectious challenge revealed differences related to the MHC-I profile of the mouse: colonization by b-Proteobacteria was enhanced in the B27tg mouse compared with B7tg and A2tg as well as with the DKO and WT control mice (Fig. 2).

Conclusion: Class I MHC expression influences survival and host immune response to oral S. typhimurium challenge in an allele-specific manner.  The endogenous gut microbial profile was distinctively different in B7tg mice, suggesting that the HLA-B27 status directly influences the composition of the gut microbiome. This raises the possibility that the clinical interface between SpA and IBD could be mediated by an interplay between host MHC and the gut microflora.

 

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hla-b27-influence-on-the-gut-microbiome/