A5.19 In African Patients with Rheumatoid Arthritis ACPA Recognise Citrullinated Fibrinogen and the Immunodominant Epitopes Borne by the Fibrin Peptides α36–50 and β60–74, Like in Caucasians. (25th February 2013) - Nogueira, L
Abstract : Background and Objectives: Although most studies concerning the Rheumatoid Arthritis (RA)-specific antibodies to citrullinated proteins (ACPA) have been performed in populations of Caucasian ancestry, anti-CCP2 antibodies were demonstrated to be also good markers for RA in African patients. In one cohort from Cameroon, frequency of the HLA-DRB1 shared epitope (SE) alleles, although higher in RA patients than in controls, was lower than in Caucasian patients. Furthermore, known Caucasian non-HLA susceptibility genes did not confer the same risk in Africans. The purposes of the present study were, first, to analyse in African patients with RA the autoantibodies to citrullinated human fibrinogen (AhFibA), then, to investigate to what extent the two citrullinated fibrin peptides α36–50 and β60–74, which bear the immunodominant epitopes, were recognised by the sera of these patients. Methods: AhFibA and autoantibodies to α36–50 and β60–74 were measured by ELISA in the serum of 56 consecutive RA patients with established disease from the Rheumatology unit of Yaoundé, Cameroon. 101 patients with other rheumatic diseases or healthy individuals were used as controls. Results: Using the 95%-specificity thresholds previously defined with a French cohort, 73% of the RA sera from African patients were positive for AhFibA ve rsus 83% in French patients. The anti-β60–74 and anti-α36–50 autoantibodies were detected in 41/56 (73%) and 25/56 (45%) African RA sera versus 71% and 51% in French RA patients, respectively. Moreover, 38/41 (93%) of the AhFibA-positive sera recognised either α36–50 and/or β60–74, as previously observed in French patients. Finally, the mean AhFibA (OD = 1.28) and anti-β60–74 (OD = 1.32) titers were significantly higher in patients with at least one copy of the HLA-DRB1 SE (17/56, 30%) than in those without SE (OD = 0.64 and 0.60, respectively; p < 0.005 and p < 0.02), while the titer of anti-α36–50 autoantibodies did not differ. Conclusions: AhFibA are markers for RA also in African patients. In these patients, autoantibodies to α36–50 and β60–74 peptides are present in proportions similar to those found in Caucasians. Like in Caucasians, they account for almost all the reactivity to fibrinogen. HLA-DRB1 SE alleles, although less common among African RA patients, are associated with higher titres of AhFibA and of auto antibodies to β60–74, suggesting that SE alleles partly control the AhFibA production, besides still unknown factors. This study shows that even in different genetic backgrounds the ACPA response is a hallmark of RA, and strongly suggests that its fine specificity to citrullinated fibrin is identical in Caucasians and Africans.