Background Although therapeutic targeting of humoral and cellular inflammatory biomarkers has improved outcomes in subsets of patients with severe RA, the identification of novel targets based on insights into disease immunopathogenesis remains a priority.
Objectives to identify relationships between radiographic damage, circulating cytokines/chemokines/growth factors, and shared epitope (SE) risk alleles classified according to the Du Montcel system
Methods DMARD-naïve, predominantly African female patients (n=142) with early RA (<2 yrs) were assessed radiographically with the modified Larsen score, measurement of serum cytokines using Luminex xMAP multiplex technology, and PCR typing of the HLA-DRB1 allele classified risk allele positive (S2 and /or S3P) or risk allele negative (S2 and/or S3D and/or X).
Results 82 (58%) carried the SE risk allele, 52% had erosive disease, and the mean Larsen score was 22(SD 12,6). There was no significant difference in the Larsen score between risk allele positive or negative group of patients. In the risk allele -ve patients, but not risk allele +ve group, Larsen scores were positively and significantly correlated with IL-7, IL-8, and VEGF (see table 1). No correlations were noted with the other circulating biomarkers. In the risk allele -ve group, IL-7 and VEGF also correlated positively and significantly with erosive disease. Inter-correlations between the various inflammatory biomarkers were generally strongest in the SE risk allele-negative group with notably increased correlations between IL 7 and IL 2/IL 4.
Conclusions IL-7 and VEGF, which promote osteoclastogenesis and neovascularization respectively, were found to correlate with erosive disease in SE risk allele-negative patients. These observations are compatible with possible differences in the immunopathogenesis of RA in SE risk allele-negative and –positive patients, identifying IL-7 and VEGF as potential targets for biologic therapy in the former group.
Hartgring SAY et al. Interleukin-7 induced immunopathology in arthritis. Ann Rheum Dis 2006;65(Suppl):69-74.
P.W. Meyer, B et al., “Circulating cytokine profiles and their relationships with autoantibodies, acute phase reactants, and disease activity in patients with rheumatoid arthritis,” Mediators of Inflammation, 2010;2010:158514, Epub 2011
Disclosure of Interest None Declared
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