title: Expression of MHC class I dimers and ERAP1 in an ankylosing spondylitis patient cohort.
abstract: The human leucocyte antigen HLA-B27 is strongly associated with ankylosing spondylitis, a form of seronegative inflammatory arthritis. In this study aspects related to several hypothesized mechanisms of disease pathogenesis have been investigated. Blood monocyte-derived dendritic cells (DC) from a small patient cohort of 29 patients with ankylosing spondylitis and one with reactive arthritis, were compared with DC from 34 healthy control subjects, of whom four were found to be HLA-B27 positive. The ability of HLA-B27 to form heavy-chain dimers reactive with monoclonal antibody HC10 was tested, along with the induction of endoplasmic reticulum (ER) stress, assessed by splicing xbp1 mRNA and immunoblotting of Immunoglobulin Binding Protein (BiP). Additionally, the protein expression levels of the ER resident aminopeptidase gene ERAP1 in patients with ankylosing spondylitis was also determined, following its recent identification as a novel disease-associated gene. No significant difference was noted in the global levels of HC10-reactive MHC class I dimers formed in either the patient or control DC populations. Stress on the ER, as determined by xbp1 mRNA splicing, was not detected but lower levels of BiP were observed in the DC from patients. Of further potential interest, in this patient cohort the expression of ERAP1 appeared to be higher in a number of patient DC samples when compared with controls, suggesting over-expression of ERAP1 as a mechanism promoting ankylosing spondylitic pathogenesis.
authors.affiliation: St Andrews Medical School, University of St Andrews, Fife Ninewells Hospital, Dundee, UK.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Campbell
authors.forename: Franziska
authors.initials: F
authors.lastname: Fettke
authors.forename: Smita
authors.initials: S
authors.lastname: Bhat
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Morley
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Powis
mesh_terms: D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D003713:Dendritic Cells / Q000276:immunology*; D019281:Dimerization; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D005805:Genes, MHC Class I / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D015778:Minor Histocompatibility Antigens; D017510:Protein Folding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013167:Spondylitis, Ankylosing / Q000235:genetics / Q000503:physiopathology*
chemical_list: D015796:HLA-B27 Antigen; D015778:Minor Histocompatibility Antigens; D000626:Aminopeptidases; C464841:ERAP1 protein, human