New insight into mechanisms of HLA-B27

This experimental study found that HLA-B27 is associated with altered cecal microbiota, a finding not shown before that can potentially provide a better understanding of the clinical diseases associated with this gene, including acute anterior uveitis.

The HLA-B27 molecule has been found to increase the risk of developing acute anterior uveitis and ankylosing spondylitis in certain human populations. However, how the HLA-B27 molecule causes this increased risk is not understood. It is known that HLA-B27 transgenic rats develop spontaneous gut and joint inflammation; but the disease does not develop if transgenic rats are raised in a germ-free environment, which hints at the involvement of the gut in the disease pathogenesis. 

In this article, the authors hypothesized that the HLA-B27 molecule somehow alters the microbiotic gut flora. Using a 16S rRNA amplification technique, they analyzed differences in gut microbiota mediated by the presence of the HLA-B27 gene in transgenic versus wild-type rats (controls).

They found significant differences in the abundance of rare bacteria among wild-type and transgenic rats. The Paraprevotella family was more abundant and the Rickenellaceae less abundant in transgenic rats compared to controls; but there was no difference when comparing more common bacteria genera (Clostridia and Helicobacter).

Furthermore, using a BRISK sequence technique that allows for evaluation of the whole gut microbiome, transgenic rats showed an increased abundance of the three main bacteria (Faecalibacterium prausnitzii, Bacteroides vulgatus and Akkermansia muciniphila) compared to controls. 

It is known that Bacteroides vulgatus can cause colitis in HLA-B27+ transgenic germ-free raised rats. Also species similar to Paraprevotella appear to influence the pathogenesis of rheumatoid arthritis in humans. 

They conclude that although this study shows microbiota differences among wild-type and transgenic rats, more studies are needed to show that these differences affect the immune system and in turn the development of inflammatory diseases.