Objective. Previously, only the HLA-DRB1 alleles have been assessed in rheumatoid arthritis (RA). The aim of the present study was to identify the key major histocompatibility complex (MHC)... Show moreObjective. Previously, only the HLA-DRB1 alleles have been assessed in rheumatoid arthritis (RA). The aim of the present study was to identify the key major histocompatibility complex (MHC) susceptibility factors showing a significant association with anti-carbamylated protein antibody-positive (anti-CarP+) RA.Methods. Analyses were restricted to RA patients who were anti-cyclic citrullinated peptide antibody negative (anti-CCP), because the anti-CCP status dominated the results otherwise. Therefore, we studied samples from 1,821 anti-CCP- RA patients and 6,821 population controls from Spain, Sweden, and the Netherlands. The genotypes for similar to 8,000 MHC biallelic variants were assessed by dense genotyping and imputation. Their association with the anti-CarP status in RA patients was tested with logistic regression and combined with inverse-variance meta-analysis. Significance of the associations was assessed according to a study-specific threshold of P < 2.0 x 10(-5).Results. The HLA-B*08 allele and its correlated amino acid variant Asp-9 showed a significant association with anti-CarP+/anti-CCP- RA (P < 3.78 x 10(-7); I-2 = 0). This association was specific when assessed relative to 3 comparator groups: population controls, anti-CarP-/anti-CCP- RA patients, and anti-CCP- RA patients who were positive for other anti-citrullinated protein antibodies. Based on these findings, anti-CarP+/anti-CCP- RA patients could be separated from other antibody-defined subsets of RA patients in whom an association with the HLA-B*08 allele has been previously demonstrated. No other MHC variant remained associated with anti-CarP+/anti-CCP- RA after accounting for the presence of the HLA-B*08 allele. Specifically, the reported association of HLA-DRB1*03 was observed at a level comparable to that reported previously, but it was attributable to linkage disequilibrium.Conclusion. These results identify HLA-B*08 carrying Asp-9 as the MHC locus showing the strongest association with anti-CarP+/anti-CCP- RA. This knowledge may help clarify the role of the HLA in susceptibility to specific subsets of RA, by shaping the spectrum of RA autoantibodies. Show less
Najm, A.; Kostine, M.; Pauling, J.D.; Ferreira, A.C.; Stevens, K.; Smith, E.; ... ; Sepriano, A. 2020
Background Multidisciplinary collaboration is defined as a collective work involving multiple disciplines and is common in clinical care and research. Our aim was to describe current clinical and... Show moreBackground Multidisciplinary collaboration is defined as a collective work involving multiple disciplines and is common in clinical care and research. Our aim was to describe current clinical and research collaboration among young specialists and to identify unmet needs in this area. Methods An online survey was disseminated by email and social media to members of the EMerging EUlar NETwork, the Young Nephrologists' Platform, the Paediatric Rheumatology European Society Emerging Rheumatologists and Researchers and the European Academy of Allergy and Clinical Immunology Junior Members. Results Of 303 respondents from 36 countries, 61% were female, 21% were aged below 30 years and 67% were aged 31-40 years. Young rheumatologists were the most represented (39%), followed by young nephrologists (24%), young paediatricians (20%), young allergologists (11%) then young internists (3%) and 3% other specialities. Collaborations were reported frequently by phone and email, also by various combined clinics while common local multidisciplinary meetings were uncommon. 96% would like to develop clinical research collaborations and 69% basic research collaborations. The majority of young specialists would be interested in online (84%) and/or 1-2 days (85%) common courses including case discussion (81%) and training workshops (85%), as well as webinars recorded with several specialists on a specific disease (96%). Conclusions This collaborative initiative highlighted wishes from young specialists for developing (1) regular local multidisciplinary meetings to discuss complex patients, (2) clinical research collaboration with combined grants and (3) multidisciplinary online projects such as common courses, webinars and apps. Show less
Objective This study aims to (1) assess the perceived need for a postdoctoral (post-doc) mentoring programme in rheumatology, (2) describe the characteristics and organisational aspects of a pilot... Show moreObjective This study aims to (1) assess the perceived need for a postdoctoral (post-doc) mentoring programme in rheumatology, (2) describe the characteristics and organisational aspects of a pilot mentoring programme implemented by the EMerging European League Against Rheumatism NETwork (EMEUNET) and (3) report mentors' and mentees' evaluation of the pilot programme.Methods An online survey was conducted among young researchers in rheumatology to evaluate the need and preferred characteristics of a post-doc mentoring initiative. Informed by the survey, a pilot programme was designed and launched. The pilot programme was evaluated with 3-month, 6-moth and 12-month surveys and interviews with mentees and a 12-month survey among mentors, after completion.Results From 275 responses (43 countries, 86% from Europe) collected, analyses were restricted to the target population (total population=158; post-docs (n=103 (65%)) and PhD students (n=55 (35%))). There was a clear need (99% positive responses) for a post-doc mentoring programme. Discussions about current and new projects, and how to lead projects were ranked as priorities in post-doc mentoring. The most desired mentor attribute was generosity and interest in helping (86%), followed by research experience (68%) and having a well-established network (66%). The pilot programme included four mentees (through competitive application) allocated to three mentors. Evaluation surveys and interviews revealed that the programme organisation and content were well appreciated by mentees and mentors.Conclusions The EMEUNET post-doc mentoring programme addresses unmet need for mentoring, is viable and appreciated by mentors and mentees. The programme structure and content are transferable to other fields where there is need for academic career mentoring. Show less