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The link of HLA-B27 with interleukin-23/interleukin-17 axis in coexisting systemic lupus erythematosus and ankylosing spondylitis

Sir, We read with great interest the contribution by Mrabet et al. They reported an unusual case of coexisting systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) with positive human leukocyte antigen (HLA)-B27 but did not explicate the exact mechanisms. We would like to suggest a possible pathomechanism in the development of the two inflammatory diseases. Interleukin (IL)-23, a heterodimer composed of IL-12p40 and IL-23p19 subunits, and IL-17A, a cytokine produced by the IL-23-maintained T helper 17 (Th 17) subset, have been implicated in a number of inflammatory autoimmune diseases such as rheumatoid arthritis and SLE. Th 17 development producing the pro-inflammatory cytokine IL-17 is promoted by IL-23. Quite recently and importantly, Bowness et al. showed that H chain dimers of HLA-B27, termed HLA-B27(2)-expressing APCs which bind the killer-cell Ig-like receptor KIR3DL2 stimulate IL17 production of KIR3DL2(þ) CD4 T cells. Strikingly, KIR3DL2(þ) CD4 T cells account for the majority of peripheral blood CD4 T cell IL-23R expression and produce more IL-17 in the presence of IL-23. These findings link HLA-B27 with IL-17 production. In the previous study of Whittingham et al., there was also an increased risk of SLE with HLA-B8/B27 (relative risk1⁄4 27.6). The result suggested that susceptibility to SLE is influenced by one or more genes in linkage disequlibrium with the HLA-antigens-DR3 haplotype. AS, the most common spondyloarthritis, is genetically associated with both HLA-B27 and IL-23R polymorphisms. Wang et al. reported that the patients with AS showed elevated levels of IL-23 and IL-17 in the serum and supernatants of cultured peripheral blood mononuclear cells and speculated that these two cytokines might be responsible for the development of AS. Wendling also supported the potential central role of the IL-23/IL-17 axis in AS and speculated that p19 IL-23 blockade might be more efficacious in a new therapeutic pathway. Therefore, there is a possibility that enhanced IL23R expression and increased production of IL-17 through KIR3DL2(þ) CD4 T cells linked with positiveHLA-B27homodimersmayplay critical roles in the pathogenesis of coexisting AS and SLE. However, further studies are necessary to elucidate the exact molecular role and signaling transduction pathway of IL-23 and IL-17 during the diseases process. The role of IL-21, a member of the type I cytokine superfamily, and IL-32, originally named natural killer cell transcript 4 (NK4), in AS and SLE should also be further evaluated in the future.