HLA-B27 Misfolding
Robert A. Colbert, MD, PhD, has been pursuing pathogenic mechanisms in HLA-B27 disease for some years and has published experimental data supporting the hypothesis that HLA-B27 is a protein misfolding disease. Many laboratories have failed to find specific arthritogenic peptides presented by the HLA-B27 molecule, an earlier alternative view. Observations leading to this theory stem directly from a pilot project of Dr. Colbert and his lab, "Antigen Presentation in HLA-B27 Transgenic Animals."
Protein misfolding may contribute to activation to of the innate immune system via the UPR response, suggesting an unusual pathogenic mechanism for an inflammatory arthritic process. As a result of these studies, many new research directions have been established. A translational component investigating the UPR response in patients with spondoarthropathies has been included in this proposed Multidisciplinary Clinical Research Center (MCRC) cycle.
Publications
Mear JP, Schreiber KL, Munz C, Zhu X, Stevanovic S, Rammensee H-G, Rowland-Jones SL, Colbert RA. Misfolding of HLA-B27 as a result of its B pocket suggests a novel mechanism for its role in susceptibility to spondyloarthropathies. J Immunol 1999; 163:6665-6670.
Dangoria NS, DeLay ML, Kingsbury DJ, Mear JP, Uchanska-Ziegler B, Ziegler A, Colbert RA. HLA-B27 misfolding is associated with aberrant intermolecular disulfide bond formation (dimerization) in the endoplasmic reticulum. J. Biol. Chem. 2002; 277:23459-23468.
Colbert RA. The immunobiology of HLA-B27: Variations on a theme. Curr. Mol. Med. 2004; 4:21-30.
