Background/Purpose:

It has been observed that ankylosing spondylitis (AS) patients have a high frequency of asymptomatic chronic gut inflammation, with as many as 60% of AS patients with evidence of microscopic gut inflammation without gastrointestinal symptoms. While much is known about the clinical relationship between AS and IBD, little is understood about the directionality of these relationships or the role of the gut in the pathogenesis of AS. This study aimed to investigate if healthy asymptomatic first-degree relatives (FDRs) of ankylosing spondylitis patients have evidence of subclinical gut inflammation that precedes development of musculoskeletal signs and symptoms of AS.

Methods:

30 healthy FDRs of AS patients between the ages of 18 and 50 years old were recruited for the purpose of this study, of which 18 are included in the current cross-sectional analysis. We collected serum biomarkers of gut inflammation including anti-Saccharomyces cerevesiae antibodies (ASCA), antineutrophil cytoplasmic antibodies (ANCA), anti-I2 (associated with anti-Pseudomonas activity), anti-Eschericia coliouter membrane porin C (anti-OmpC) and anti-flagellin antibodies (anti-CBir1), as well as stool samples to measure fecal calprotectin. Clinical data about symptoms and signs of ankylosing spondylitis was obtained using the Toronto Axial Spondyloarthritis Questionnaire in Inflammatory Bowel Disease (IBD.) Finally, we obtained a pelvic MRI on all subjects using STIR (Short TI Inversion Recovery) sequences to rule in or out the presence of asymptomatic axial spondyloarthritis. FDRs with no MRI evidence of disease will be followed and assessed yearly for the development of AS.

Results:

Of 18 FDRs included in the current analysis, six were found to be HLA B27 positive. Six FDRs (33%) reported back pain, and four FDRs (22%) reported heel pain. No participants reported other extra-articular manifestations and no participants reported gastrointestinal symptoms. On MRI, two FDRs (11%) were found to have evidence of definite sacroiliitis. Four FDRs (11%) were found to have a fecal calprotectin level which was in the upper range of normal. Six FDRs (33%) were found to have at least one positive IBD antibody, five of which have CBir positivity (27%). Two FDRs (11%) had a positive ASCA antibody.  Of the six FDRs with a positive IBD antibody, 50% were HLA B27 positive and none reported back pain, gastrointestinal symptoms, or had MRI evidence of sacroiliitis.

Conclusion:

A substantial proportion of healthy FDRs of AS patients have an elevated serum IBD antibody profile, specifically with respect to anti-CBir1, without evidence of clinical IBD, suggestive of mucosal dysregulation.  This study will contribute to our understanding of the directionality of the AS-gut inflammation relationship as well as the role of the gut in the etiology of AS. With increasing understanding of whether gut inflammation precedes AS, we can develop a prediction tool for determining who is at risk of developing the disease and begin to intervene at the earliest possible stage in order to delay the onset of debilitating symptoms.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mucosal-dysregulation-in-first-degree-relatives-of-ankylosing-spondylitis-patients/