Immunochemical characterization of Klebsiella antigens which specifically modify an HLA-B27-associated cell-surface...

Culture filtrates of some Klebsiella isolates contain a factor(s) capable of specifically modifying the HLA-B27-positive lymphocytes of normal individuals, resulting in a phenotypic change similar to that seen on lymphocytes from patients with ankylosing spondylitis (AS). To further delineate the nature of the interaction between HLA-B27 and some Klebsiella products we have undertaken a chemical characterization of B27+AS+-cross-reactive Klebsiella antigens from the culture filtrate and the bacterial cell-membrane. Biogel P-100 chromatography of the Klebsiella K43-derived modifying factor from the culture filtrate and from an NP-40-solubilized membrane extract gave a molecular weight of 26,000-30,000. Isoelectric focusing revealed that the modifying factor had an isoelectric point of approximately 5.4. Membrane-associated modifying factor activity was found only in outer-membrane preparations indicating that the cross-reactivity between Klebsiella K43 and B27+AS+ cells is defined, at least in part, by outer-membrane antigens. These studies demonstrate that membrane components of Klebsiella K43 share antigenic determinants with a modifying factor, which is released into the culture medium, and that these components are capable of specifically altering the HLA-B27 antigen or an associated cell-surface structure. Such a modification occurring in vivo following exposure to Klebsiella, or to antigenically related organisms, could explain the triggering of the B27-associated arthropathies such as AS.