8 research outputs found
A loss-of-function <i>IFNAR1</i> allele in Polynesia underlies severe viral diseases in homozygotes
International audienceGlobally, autosomal recessive IFNAR1 deficiency is a rare inborn error of immunity underlying susceptibility to live attenuated vaccine and wild-type viruses. We report seven children from five unrelated kindreds of western Polynesian ancestry who suffered from severe viral diseases. All the patients are homozygous for the same nonsense IFNAR1 variant (p.Glu386*). This allele encodes a truncated protein that is absent from the cell surface and is loss-of-function. The fibroblasts of the patients do not respond to type I IFNs (IFN-α2, IFN-Ï, or IFN-ÎČ). Remarkably, this IFNAR1 variant has a minor allele frequency >1% in Samoa and is also observed in the Cook, Society, Marquesas, and Austral islands, as well as Fiji, whereas it is extremely rare or absent in the other populations tested, including those of the Pacific region. Inherited IFNAR1 deficiency should be considered in individuals of Polynesian ancestry with severe viral illnesses
High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohnâs Disease
International audienceBackground & AimsLittle is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohnâs disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohnâs perianal disease followed up in the Cancers Et Surrisque AssociĂ© aux Maladies Inflammatoires Intestinales En France (CESAME) cohort.MethodsWe collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohnâs disease. Subjects were followed up for a median time of 35 months (interquartile range, 29â40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex.ResultsAmong the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohnâs lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistulaârelated adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistulaârelated adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohnâs disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03).ConclusionsIn an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohnâs disease have a high risk of anal cancer, including perianal fistulaârelated cancer, and a high risk of rectal cancer