title: How to translate basic knowledge into clinical application of biologic therapy in spondyloarthritis.
abstract: Spondyloarthritis (SpA) is a family of many diseases, and these diseases share some clinical, genetic, and radiologic features. The disease process in the spine at the beginning is spinal inflammation, in which TNF α is the principal cytokine involved. Therefore, the dramatic clinical and pathologic response of anti-TNF α therapy in SpA is based upon the presence of increased TNF α in synovial tissues and sacroiliac joints, which perpetuates chronic inflammation. The increased Toll-like receptors (TCR) 2 and 4 in the serum, peripheral blood mononuclear cells, or synovial tissues of ankylosing spondyloarthritis (AS) or SpA patients suggest that SpA is highly associated with innate immunity. Any drug including anti-TNF α blocker which can downregulate the TCR, infiltrated neutrophils, or CD163+ macrophages in the synovial tissue is the rationale for the management of SpA. Like rheumatoid arthritis, the increased TH22 and TH17 cells either in blood, synovial fluid, or synovial tissues were also demonstrated in SpA. Thus, TH17 and TH22 may be reasonable cellular targets for therapeutic intervention. Drugs (anti-IL6R or anti-IL6) which can reduce the binding of IL6 and IL6R to the cell surface may be beneficial in SpA. Many proteins are implicated in the new bone formation (syndesmophyte) or ankylosis in AS or SpA. The enhanced BMP and Wnt pathway will activate osteoblasts which promote the new bone formation. However, no drug including anti-TNF α can stop or prevent the syndesmophyte in AS. In summary, looking for new targeting therapies for either anti-inflammation (beyond anti-TNF) or anti-bone formation (including anti-TGF β or PDGF) is warranted in the future.
authors.affiliation: Division of Allergy-Immunology-Rheumatology, Department of Medicine, Veterans General Hospital, No. 201, Section 2, Shipai Road, Beitou District, Taipei 112, Taiwan. ctchou1007@gmail.com
authors.forename: Chung-Tei
authors.initials: CT
authors.lastname: Chou
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D025241:Spondylarthritis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013582:Synovial Fluid / Q000187:drug effects* / Q000276:immunology; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D000098902:CD163 Antigen; D000093242:Interleukin-6 Inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015850:Interleukin-6; D011956:Receptors, Cell Surface; D019947:Receptors, Interleukin-6; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000098902:CD163 Antigen; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human