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Genotyping can predict disease outcomes in rheumatoid arthritis patients
Date:6/13/2014

nts with 2811 X-rays); the Early Rheumatoid Arthritis Study-ERAS (421 patients with 3758 X-rays); and a cohort from 57 UK centres-BRAGGSS* (1846 patients with treatment response) were used to assess whether HLA-DRB1 positions 11, 71, 74 could predict radiological outcome, anti-TNF response and mortality in patients with RA.

The finding that the amino acid valine at position 11 of HLA-DRB1 (Val11) was the strongest independent genetic determinant of radiological damage in RA was replicated in separate cohorts. Three positions 11, 71 and 74, which together define 16 haplotypes (combinations of gene segments), were strongly associated with disease outcome, superseding the shared epitope. The hierarchy, ranging from risk to protective effects, was perfectly correlated with that observed for disease susceptibility.

HLA-DRB1 haplotypes associated with RA susceptibility and severe outcome were also predictors of good treatment response with anti-TNF therapy. For example, the Val11Lys71Ala74-haplotype, carried by 52% of patients, was associated with a good EULAR response. On average, 17 patients needed to be treated with anti-TNF to see one more patient responding better, based solely on the carriage of this haplotype. Both all-cause and cardiovascular mortality was also predicted by the 16 haplotypes.

HLA typing was determined using a reverse dot-blot method or dense genotyping of the HLA region by the ImmunoChip array, followed by imputation. Longitudinal modelling of the presence of erosions was performed with Generalized Estimating Equation (GEE) models, whilst the Larsen score was modelled with Generalized Linear Latent and Mixed Modelling (GLLAMM).


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Contact: EULAR Press Office
eularpressoffice@cohnwolfe.com
44-078-801-73209
European League Against Rheumatism
Source:Eurekalert

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