Secretory autoantibodies in primary biliary cirrhosis (PBC).
It is unclear how breakdown in immune tolerance to the ubiquitous self-antigen pyruvate dehydrogenase complex (PDC), seen in the autoimmune liver disease PBC, gives rise to tissue damage with such a limited distribution (restricted to the liver and salivary and lachrymal glands). One property shared by these tissues is the ability to export secretory IgA by the process of transcytosis. The aim of this study was to address whether active transcytosis of anti-PDC IgA occurs across epithelial surfaces in PBC, a finding that might implicate mucosal specific immune mechanisms in the pathogenesis of this disease. Parotid saliva was collected from PBC patients (n = 44), normal controls (n = 28) and PBC patients post-liver transplantation (n = 11). IgA and secretory component-positive antibodies specific for human PDC were quantified by ELISA and immunoblotting. PBC patients (but not control subjects) had anti-PDC IgA in their saliva. The strong correlation seen between titres detected using anti-IgA and anti-secretory component antibodies suggests that this is predominantly secretory IgA reaching the saliva by the active process of epithelial transcytosis. Titres of anti-PDC IgA remain high in PBC patients saliva post-liver transplant. Findings from studies of IgA in viral infection models raise the possibility that anti-PDC IgA could, whilst undergoing transcytosis, bind to newly translated PDC components in the cytoplasm of the epithelial cells transporting them out of the cell and inducing metabolic damage. This model would, if correct, help to explain the mechanism and tropism of tissue damage in PBC and the aberrant pattern of expression of PDC on the apical surface of biliary and salivary epithelial cells reported in this disease.
Palmer
J M
JM
Centre for Liver Research and School of Biochemistry and Genetics, University of Newcastle, Newcastle-upon-Tyne, UK.
Doshi
M
M
Kirby
J A
JA
Yeaman
S J
SJ
Bassendine
M F
MF
Jones
D E
DE
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000276:immunology; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000503:physiopathology; D008875:Middle Aged; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology*; D012463:Saliva / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D007071:Immunoglobulin A, Secretory; D011768:Pyruvate Dehydrogenase Complex