Association between secretor status and Lewis phenotype with seronegative spondyloarthritis as indicator of autoimmunity

Abstract

The classical paradigm of autoimmune pathogenesis involving specific genetic makeup and exposure to environmental triggers has been challenged recently by the addition of a third element, the loss of intestinal barrier function. Regardless of HLA B27 phenotype or gastrointestinal symptoms, evidence of ileitis, ileocolitis or colitis exists in patients with spondyloarthropathy. The FUT2 secretory gene is a strong candidate for Crohn's susceptibility by shaping the functional states of mucosal microbiota and may thus have influence on the release of zonulin, the main regulator of gut permeability. Gram negative bacteria precipitate and may be involved in the pathogenesis of spondyloarthropathies. Susceptibility to many infectious agents is associated with ABO blood group or secretor state. Patients who cannot secrete ABO and Lewis blood group antigens into body fluids, an ability controlled by a single gene on chromosome 19, are known to be at increased risk of certain autoimmune diseases associated with human leukocyte antigen (HLA) markers. Lewis (Le) blood group phenotype can be used to infer secretor status. The objective of this study was to determine the distribution of secretor state and Lewis blood group phenotype in patients with seronegative spondyloarthropathies and healthy control subjects. Hundred and ten (110) patients with seronegative spondyloarthropathies (58 females and 52 males) and 103 control (74 males and 29 females) subjects participated in this study. Samples of saliva and blood were subjected to haemagglutination inhibition tests for determination of secretor status and Lewis phenotype. A total of 92(84%) patients and 92 (89%) control subjects were secretors while 18 (16%) patients and 11 (11%) control subjects were non-secretors. There was no statistically significant difference (?2 1,461 p<0,05 and degrees of freedom 1) in distribution of secretor status in comparison to seronegative spondyloarthropathies by comparing two observed populations. Seven patients had modified (reduced) expression of Lewis b antigen on their erythrocytes. Reduction of Lewis b antigen expression was not observed on erythrocytes of healthy subjects. Reduced expression of Lewis b antigen could be a consequence of the inflammatory process within the gut and it also suggests several pathogenic mechanisms which may be relevant to the synthesis of Lewis antigens inside the gut or its absorption on erythrocytes in patients with spondyloarthropathy.