In contrast, the elevated levels of soluble Sema4D protein in rheumatoid arthritis are not due to increased Sema4D mRNA expression but are driven by a disintegrin and metalloproteinase with thrombospondin motif 4 (ADAMTS4)-mediated proteolytic cleavage of membrane-bound Sema4D [35]. This evidence concerns the gene SEMA4D and rheumatoid arthritis.