Structural Identity of Human Histocompatibility Leukocyte Antigen-B27 Molecules from Patients with Ankylosing Spondylitis and Normal Individuals

Abstract

A B S T R A C T Although the association between human histocompatibility leukocyte antigen (HLA) B27 and ankylosing spondylitis is the prototype of HLAdisease association, the mechanism underlying these associations has not been determined. We have investigated the possibility that the B27 molecules from patients with ankylosing spondylitis are different from those of normals, and only the "different" molecules predispose the individual to disease. Biosynthetically radiolabeled HLA-B27 molecules from patients with ankylosing spondylitis and normal individuals were compared by two-dimensional gel electrophoresis and tryptic peptide mapping with high pressure liquid chromatography. Extensive charge heterogeneity in the 45,000-dalton heavy chain was detected when B27 molecules were analyzed by two-dimensional gel electrophoresis; the charge heterogeneity was reduced, but not eliminated, when the B27 molecules were treated with neuraminidase to remove sialic acid residues before analysis. No structural difference in the B27 molecules from an ankylosing spondylitis patient and a normal individual were detected by two-dimensional gel electrophoresis. Analysis of [3H]leucine-labeled and[3H]arginine-labeled tryptic peptides and chymotryptic peptides of the trypsin insoluble material by reverse-phase high pressure liquid chromatography revealed identity of the B27 molecules from ankylosing spondylitis patients and normal individuals. These studies indicate that development of akylosing spondylitis in only some B27 positive individuals is not at-

Specific Cell‐Mediated Responses to Bacterial Antigens and Clinical Correlations in Reactive Arthritis, Reiter's Syndrome and Ankylosing Spondylitis

“…Evidence in favor of structural identity of the B27 antigen in AS, RS and controls has been shown using monoclonal antibody (Grumet et al 1981). Studies using biosynthetically radiolabelled B27 molecules in AS and controls showed no difference by two-dimensional gel electrophoresis, and neither did [^H] argininelabelled tryptic and chymotryptic peptides of trypsin-insoluble material by reverse-phase high pressure liquid chromatography (Karr et al 1982). Evidence in favor of epitope similarity of the B27 antigen and certain bacteria has been the demonstration of cross-reactivity of klebsiella, shigella and yersinia antigens with determinants recognized by monoclonals B27M1 and -M2 (van Bohemen et al 1984).…”

Ankylosing Spondylitis, HLA-B27 and Klebsiella - An Overview: Proposal for Early Diagnosis and Treatment

“…Studies of the HLA-B27 molecule by two-dimensional gel electrophoresis [11] DNA sequencing [12] and restriction fragment length polymorphism [13] have all shown no molecular differences in this genetic marker between patients with AS and healthy controls. Furthermore, using HLA-B27 specific monoclonal antibodies, no disease-associated variant of HLA-B27 has been observed in AS [14].…”

Klebsiella 'modifying factor': binding studies with HLA-B27+ and B27- lymphocytes.

“…However, such a polymorphism has not been detected in two studies using two-dimensional PAGE and tryptic and chymotryptic peptide mapping. 19 20 In fact no difference in structure of B27 was noted between subjects with AS and normal subjects. The polymorphism in B27 structure defined by B27m2 (12% of individuals typed as B27+ by conventional means lack the determinant detected by this monoclonal antibody) does not correlate with susceptibility to AS.'…”