Clinical and immunogenetic characteristics of European multicase rheumatoid arthritis families

Objective-To describe the characteristics of a new set of European families with affected sib pairs (ASP) collected by the European Consortium on Rheu matoid Arthritis Families (ECRAF) to replicate the results of our first gen ome scan. Potential gradients for disease severity in Europe and concordanc e within families were studied. Patients and methods-From 1996 to 1998 European white families with at leas t two affected siblings were enrolled in the study. Demographic (sex, age a t onset), clinical data (rheumatoid factor (RF), disease duration, erosive disease, extra-articular features (EF)), and HLA-DRB1 oligotyping were anal ysed. Results-565 patients with rheumatoid arthritis (RA), belonging to 271 famil ies including 319 affected 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 year s), and RF positivity (79%) were similar among the countries. Differences w ere found in disease duration (11-18 years) and in the prevalence of erosiv e disease (70-93%), nodules (15-44%) subjective Sjogren's syndrome (5-38%), and EF (3-16%) (p<0.05 in all cases). A total of 22% RA sibs were shared e pitope (SE) negative, whereas 47% and 30% carried one and two SE alleles re spectively. Carriage of SE differed widely among countries (p<0.0001): no S E alleles (6-36%), one allele (43-60%), and two alleles (20-39%). SE encodi ng alleles were mainly DRB1*04 in the Netherlands and Belgium, whereas SE c arriage was less common and evenly distributed between DRB1*01, *04, and *1 0 in Mediterranean countries. No accordance within families was found eithe r in age/calendar year of onset (intraclass correlation coefficient <0.50) or in clinical and radiological features (<kappa><0.22). Conclusions-The differences in RA characteristics between European countrie s and within families underline the heterogeneity of the disease. No clear cut gradient of disease severity was seen in Europe.