Background-Genetic anticipation has been proposed to explain observed age diVerences at diagnosis of Crohn's disease in aVected parents and oVspring. Aims-To compare aVected parent-child pairs with Crohn's disease and ulcerative colitis with a control group of non-familial patients with inflammatory bowel disease (IBD) in order to quantify whether ascertainment bias could account for this eVect. Methods-137 aVected parent-child pairs from 96 families and 214 patients with sporadic IBD were studied. Age at onset of symptoms and diagnosis were ascertained by interview and disease confirmed from clinical records. Results-Of the 137 aVected parent-child pairs, 50 had Crohn's disease only, 51 had ulcerative colitis only, and in 36, one had Crohn's disease and the other ulcerative colitis. The median age of parents at diagnosis was 17.5 years older, 16 years older, and 18 years older in the Crohn's disease, ulcerative colitis, and mixed disease families respectively (p<0.001 in each case). These observed age diVerences were compatible with those predicted from the regression lines of years of birth against age at diagnosis for the non-familial IBD patients. No evidence was found for an eVect of parental sex on age at diagnosis or disease extent in oVspring. Conclusions-There was no evidence of genetic anticipation or genomic imprinting of age at diagnosis in this sample of IBD families. Ascertainment bias is responsible for the age diVerences at diagnosis between aVected parents and children. (Gut 1999;44:808-811)
There is substantial interest regarding the perceived risk that immunomodulator and biologic therapy could have on COVID-19 disease severity among patients with inflammatory bowel disease (IBD) and clinicians. In this study, we show that infliximab/thiopurine combination therapy is associated with significantly lower IgA, a range of lower IgG responses as well as impaired neutralising antibody responses, compared to responses observed in healthy individuals. We also demonstrate that whilst IgG responses were significantly reduced in individuals with IBD treated with infliximab or vedolizumab monotherapy compared to healthy controls, there was no significant reduction in IgA and neutralising antibody responses. As neutralising antibody responses correlate with protection, this observation may provide the mechanistic explanation for the observation reported by the SECURE-IBD study that individuals on infliximab/thiopurine combination therapy were at greater risk of severe COVID-19 outcomes than patients on monotherapy.
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