Evaluation de l'éducation thérapeutique des patients atteints de polyarthrite rhumatoïde sous anti-TNF dans le service de rhumatologie du CHU de Caen

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

Women with rheumatoidarthritis have higher lifetime professional and non-professional exposure to silica dust compared to french general population

Background Occupational exposure to silica dust is associated with increased risk of developing ACPA positive Rheumatoid arthritis (RA). Little is known about non-occupational exposure, as there are no available tools to assess it in clinical practice.The Dust Exposure Life-Course Questionnaire (DELCQ), developed within the SILICOSIS project, a European Research Council Advanced Grant, provides clinical research with a tool derived from social sciences. The DELCQ allows to quantify both occupational and non-occupational (e.g. body care; hobbies such as DIY, woodworking, stone cutting, etc..) exposure to silica and some other inorganic particles during the whole lifetime.In the DELCQ, the identification of sources of exposure is grounded on an extensive list of products and activities summed up by the International Agency on Research on Cancer and on a wide overview of the literature addressing silica exposure and silica-related (or suspected-to-be-related) diseases.Objectives To explore occupational and non-occupational silica exposure in a series of consecutive RA patients and the association of quantified silica dust exposure with major disease features (ACPA positivity) or outcomes (erosive disease).Methods The DELCQ was administered to 97 consecutive RA patients (77F, 20M, mean age 59.1+/- 13.3 yrs.,75 ACPA positives, 66 with erosive disease) attending the rheumatology department of Avicenne Hospital (Bobigny, FRANCE). The DELCQ scores of patients were compared to those of 388 controls, matched for sex, age and smoking status, from a 2739-subject national cohort, representative of the general French population (ELIPSSilice). Within RA subjects, the association of the scores with ACPA positivity and with erosive disease was assessed after adjustment for tobacco use.Results RA patients had higher median scores of occupational (10 [0, 17] vs. 0 [0, 4]) exposure vs. controls (p5 pack/y vs. nonsmokers or smokers <5 pack/y), neither professional of non-professional scores were associated with erosive disease, despite a strong negative interaction with tobacco use.Conclusion Women with RA have higher professional and nonprofessional lifetime exposure to silica dust compared to age, and sex-matched subjects from the French general population. In this series, constituted mainly of non-smoking women, exposure to silica may be a relevant environmental factor for the development of RA. Higher occupational exposure in RA is confirmed in men with RA. Neither occupational nor non-occupational exposure was associated with ACPA positivity or erosive disease, likely due to the high prevalence these features in the patient series

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old