‘Three-way interaction’ found between HLA-B27, male sex, sacroiliitis development in IBD
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CHICAGO — In patients with inflammatory bowel disease, a “strong and consistent three-way interaction” was identified between HLA-B27, male sex and the development of sacroiliitis, according to data presented at Digestive Disease Week.
Sacroiliitis occurs in approximately 20% of patients with IBD, often aligned with male sex and HLA-B27 status; however, large-scale studies on the pathogenesis of this extraintestinal manifestation of IBD are still lacking.
“Our interest is the overlap of immune-mediated inflammatory diseases,” Dermot McGovern, MD, PhD, director of translational research at the Inflammatory Bowel Disease Center and Immunobiology Research Institute at Cedars-Sinai Medical Center, told Healio. “We wanted to see how frequent sacroiliitis was in IBD patients and what the relationship was to HLA-B27, which has a strong association with spondylitis in IBD.”
To determine the effect of HLA-B27 status and gender on the development of sacroiliitis in IBD patients, McGovern and colleagues examined data from two independent cohorts of IBD patients with European ancestry: the Cedars MIRAID cohort (n = 991) and the SHARE cohort (n = 3,497). The researchers determined sacroiliac joint status of patients either by chart review or blinded review of CT abdomen/pelvis by a musculoskeletal radiologist; HLA-B27 status of the cohorts was established through genotyping the HLA region on the Illumina ImmunoChip.
McGovern and colleagues then performed logistic regression with adjustment for principal components from population stratification analyses to ascertain the association between HLA-B27 and sacroiliitis.
According to a meta-analysis of the two study cohorts, researchers identified a strong association between HLA-B27 and sacroiliitis only in male patients with Crohn’s disease (OR = 7.72, P = 4.026E-12) and significant interaction (OR = 8.26, P = 3.52E-8), yet no association with other subgroups, such as female patients, female patients with Crohn’s disease or male patients with ulcerative colitis.
“We identified that there is a genetic interaction between sex and HLA-B27,” McGovern told Healio. “There was a strong and consistent three-way interaction between HLA-B27, male sex and IBD subtype in development of sacroiliitis in IBD patients. Within male Crohn’s disease patients [who are] HLA-B27 carriers, up to 26% of individuals have sacroiliac joint inflammation.”
In the MIRAID cohort, McGovern and colleagues reported a “striking difference” in the frequency of HLA-B27 allele between male patients with Crohn’s disease and sacroiliitis (0.13) vs. no sacroiliitis (0.025; OR = 9.32 after adjustment for population structure; P = 2.84E-7). This same correlation was absent for women with CD (OR = 1.15, P = .895), men with UC (OR = 1.57, P = .702) and women with UC (OR = 0.84, P = .843).
Similarly, in the SHARE cohort, the researchers identified this same pattern between HLA-B27 and sacroiliitis only in male patients with CD (OR = 6.58, P = 2.95E-6), but lacking in women with CD (P = .818), men with UC (P = .527) and women with UC (P = .975).
“If you look for inflammation in the sacroiliac joints, it is much more common than if it’s just diagnosed clinically,” McGovern said “As IBD doctors, we are not looking hard enough for this extraintestinal manifestation, and this is important because the presence or absence of this would direct our therapy.”
He advised gastroenterologists to “think about asking [your] patients about joint symptoms, and make sure your radiologists are looking at joints, as well as other organs when they review CTs and MRI scans. Think musculoskeletal health as well as gut health for our IBD patients.”
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McGovern DPB., et al. Abstract Mo1772: Sacroiliitis in IBD patients: A strong and consistent interaction between HLA-B27, gender and CD/UC status. Presented at: Digestive Disease Week; May 6-9, 2023; Chicago (hybrid).
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