A HEV-restricted sulfotransferase is expressed in rheumatoid arthritis synovium and is induced by lymphotoxin-α/β and TNF-α in cultured endothelial cells

We examined the expression of GlcNAc6ST-2 in relationship to the MECA-79 epitope in rheumatoid arthritis (RA) synovial vessels. Expression of GlcNAc6ST-2 was specific to RA synovial tissues as compared to osteoarthritis synovial tissues and localized to endothelial cells of HEV-like vessels and small flat-walled vessels. Double MECA-79 and GlcNAc6ST-2 staining showed colocalization of the MECA-79 epitope and GlcNAc6ST-2. We further found that both TNF-α and lymphotoxin-αβ induced GlcNAc6ST-2 mRNA and protein in cultured human umbilical vein endothelial cells.These observations demonstrate that GlcNAc6ST-2 is induced in RA vessels and provide potential cytokine pathways for its induction. GlcNAc6ST-2 is a novel marker of activated vessels within RA ectopic lymphoid aggregates. This enzyme represents a potential therapeutic target for RA.Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial membrane that leads to the destruction of cartilage and bone tissues. The major cellular components of the inflammatory infiltrate in RA synovium are T cells, macrophages, B cells, and dendritic cells (DCs) [1]. Tissue-infiltrating lymphocytes are often arranged in follicles which exhibit variable degrees of germinal center (GC) reactions [2-4]. These highly organized structures are similar to secondary lymphoid organs, and the process is referred to as lymphoid neogenesis [5,6]. In RA, this ectopic formation of lymphoid structures correlates with the expression of lymphotoxin-β (LT-β) and homing chemokines such as BLC (CXCL13) and SLC (CCL21), recapitulating the developmental process of lymphoid organogenesis [7].The recruitment of cellular elements to secondary lymphoid organs relies on interactions between circulating leukocytes and the specialized endothelium of high endothelial venules (HEV), which are exclusive to these organs under physiological conditions. The interaction of L-selectin on lymphocytes with sulfated glycoprot