Co-expression of CD21L and IL17A defines a subset of rheumatoid synovia, characterised by large lymphoid aggregates and high inflammation

OBJECTIVE: To determine whether the expression of IL17A and CD21L genes in inflamed rheumatoid synovia is associated with the neogenesis of ectopic lymphoid follicle-like structures (ELS), and if this aids the stratification of rheumatoid inflammation and thereby distinguishes patients with rheumatoid arthritis that might be responsive to specific targeted biologic therapies. METHODS: Expression of IL17A and CD21L genes was assessed by RT-PCR, qRT-PCR and dPCR in synovia from 54 patients with rheumatoid arthritis. A subset of synovia (n = 30) was assessed by immunohistology for the presence of CD20(+) B-lymphocytes and size of CD20(+) B-lymphocyte aggregates as indicated by maximum radial cell count. The molecular profiles of six IL17A(+)/CD21L(+) and six IL17A(-)/CD21L(-) synovia were determined by complementary DNA microarray analysis. RESULTS: By RT-PCR, 26% of synovia expressed IL17A and 52% expressed CD21L. This provided the basis for distinguishing four subgroups of rheumatoid synovia: IL17A(+)/CD21L(+) (18.5% of synovia), IL17A(+)/CD21L(-) (7.5%), IL17A(-)/CD21L(+) (33.3%) and IL17A(-)/CD21L(-) (40.7%). While the subgroups did not predict clinical outcome measures, comparisons between the synovial subgroups revealed the IL17A(+)/CD21L(+) subgroup had significantly larger CD20+ B-lymphocyte aggregates (P = 0.007) and a gene expression profile skewed toward B-cell- and antibody-mediated immunity. In contrast, genes associated with bone and cartilage remodelling were prominent in IL17A(-)/CD21L(-) synovia. CONCLUSIONS: Rheumatoid synovia can be subdivided on the basis of IL17A and CD21L gene expression. Ensuing molecular subgroups do not predict clinical outcome for patients but highlight high inflammation and the predominance of B-lymphocyte mediated mechanisms operating in IL17A(+)/CD21L(+) synovia. This may provide a rationale for more refined therapeutic selection due to the distinct molecular profiles associated with IL17A(+)/CD21L(+) and IL17A(-)/CD21L(-) rheumatoid synovia.