Clinical and immunogenetic characteristics of European multicase rheumatoid arthritis families

Abstract

Objective-To describe the characteristics of a new set of European families with aVected sib pairs (ASP) collected by the European Consortium on Rheumatoid Arthritis Families (ECRAF) to replicate the results of our first genome scan. Potential gradients for disease severity in Europe and concordance within families were studied. Patients and methods-From 1996 to 1998 European white families with at least two aVected siblings were enrolled in the study. Demographic (sex, age at onset), clinical data (rheumatoid factor (RF), disease duration, erosive disease, extraarticular features (EF)), and HLA-DRB1 oligotyping were analysed. Results-565 patients with rheumatoid arthritis (RA), belonging to 271 families including 319 aVected sib pairs (ASP) were collected. Belgium, France, Italy, the Netherlands, Portugal, and Spain contributed 20, 96, 52, 24, 9, and 70 families, respectively. Sex (78% women), age at onset (mean 44 years), and RF positivity (79%) were similar among the countries. DiVerences were found in disease duration (11-18 years) and in the prevalence of erosive disease (70-93%), nodules (15-44%), subjective Sjögren's syndrome (5-38%), and EF (3-16%) (p<0.05 in all cases). A total of 22% RA sibs were shared epitope (SE) negative, whereas 47% and 30% carried one and two SE alleles respectively. Carriage of SE diVered widely among countries (p<0.0001): no SE alleles (6-36%), one allele (43-60%), and two alleles (20-39%). SE encoding alleles were mainly DRB1*04 in the Netherlands and Belgium, whereas SE carriage was less common and evenly distributed between DRB1*01, *04, and *10 in Mediterranean countries. No concordance within families was found either in age/calendar year of onset (intraclass correlation coefficient <0.50) or in clinical and radiological features ( <0.22). Conclusions-The diVerences in RA characteristics between European countries and within families underline the heterogeneity of the disease. No clear cut gradient of disease severity was seen in Europe.

Familial disease, the HLA-DRB1 shared epitope and anti-CCP antibodies influence time at appearance of substantial joint damage in rheumatoid arthritis

“…There is a wide range of results on the association between familial RA and radiographic progression. Some studies report a lack of association [17][18][19][20][21][22][23] and others a considerable influence of familial RA on damage progression [24][25][26][27][28][29]. These apparently contradictory results may be explained by differences in the definitions of familial RA and radiographic progression across studies, and in the study designs and statistical methods used ( Table 3).…”

“…The term ''familial'' has been used arbitrarily in the reports on the genetic epidemiology of autoimmune diseases, which causes difficulties in the interpretation of results [30]. Some reports make a distinction between familial and sporadic disease based solely on the number of siblings affected [24,28,30]. In the current study, we use the term ''familial'' to describe the aggregation of RA in FDRs.…”

HLA B27 as Predisposition Factor to Suffer Age Related Macular Degeneration

“…This indicates that in our population, the association is really with B27 and not by a mistake due to linkage disequilibrium with Cw0701 (27,28). On the other hand, the mentioned study is of an English population and therefore different from the group we studied, which was a Mediterranean population of the south of Spain (29)(30)(31). However, great numbers of studies that associate HLA-B27 with different pathologies do exist (32)(33)(34), such as spondyloarthropathies (mainly the ankylosing spondylitis).…”

IRF5 rs2004640-T allele, the new genetic factor for systemic lupus erythematosus, is not associated with rheumatoid arthritis

“…13 All clinical data were reviewed by rheumatologists of our team. Families with an additional affected sibling and patients with RA aged ,18 years were excluded.…”