Ankylosing spondylitis: from cells to genes

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown etiology, though it is considered an autoimmune disease. HLA-B27 is the risk factor most often associated with AS, and although the mechanism of involvement is unclear, the subtypes and other features of the relationship between HLA-B27 and AS have been studied for years. Additionally, the key role of IL-17 and Th17 cells in autoimmunity and inflammation suggests that the latter and the cytokines involved in their generation could play a role in the pathogenesis of this disease. Recent studies have described the sources of IL-17 and IL-23, as well as the characterization of Th17 cells in autoimmune diseases. Other cells, such as NK and regulatory T cells, have been implicated in autoimmunity and have been evaluated to ascertain their possible role in AS. Moreover, several polymorphisms, mutations and deletions in the regulatory proteins, protein-coding regions, and promoter regions of different genes involved in immune responses have been discovered and evaluated for possible genetic linkages to AS. In this review, we analyze the features of HLA-B27 and the suggested mechanisms of its involvement in AS while also focusing on the characterization of the immune response and the identification of genes associated with AS.

Figure 1

Proposed theories to explain the molecular pathogenic role of HLA-B27 in AS.

Figure 2

Possible role of Th17 in AS: dendritic cells (DC) could present an arthritogenic peptide derived from microbial pathogens or self-antigens to T_H0 cells. The differentiation of these T cells could be influenced by IL-17 secreted by NK cells that recognize HLA-B27 homodimers and mast cells to induce the differentiation to T_H17 cells that are involved in inflammation by molecules secreted, such as IL-6 and IL-8.