title: Autoantibodies in human chronic graft-versus-host disease after hematopoietic cell transplantation.
abstract: Primary biliary cirrhosis (PBC) and graft-versus-host disease (GVHD) are thought to have common immunopathologic features and previous studies have reported that 5.2 to 81% of patients with chronic GVHD after allogeneic hematopoietic cell transplant have antimitochondrial antibodies (AMA). We studied a total of 89 patients with chronic GVHD and 60 controls for AMA reactivity by ELISA and immunoblotting using recombinant PDC-E2, BCOADC-E2, and OGDC-E2, immunoblotting of beef heart mitochondrial proteins, and reactivity to nuclei, smooth muscle (ASMA), ribonucleoprotein JO-1, extractable nuclear antigen, nuclear proteins SSA/ SSB, ribonucleic P proteinase III, cardiolipin (ACA), liver kidney microsomal, thyroid microsomal, myeloperoxidase, and the reactivity of rheumatoid factor. A subset of 60 chronic GVHD sera were tested for reactivity to gp210 and LBR. Finally, liver tissue from patients with chronic GVHD and PBC was studied by immunohistochemistry to determine whether there was comparable abnormal apical staining of biliary epithelial cells using PDC-E2-specific monoclonal antibodies. Surprisingly, there were no AMA found in the sera from the 89 patients with chronic GVHD. Review of published data on AMA in GVHD suggests that previous results were primarily false positives. In contrast, sera from the patients with GVHD did have a variety of other autoantibodies and, in particular, 20/89 (22.4%) positive ANA, 23/89 (25.8%) positive ASMA, and 9/89 (10.1%) positive ACA. The other autoantibodies assayed were not statistically different from controls. Finally, abnormal biliary epithelial luminal staining of bile ducts was found, as expected, in liver tissue of patients with PBC but was absent in chronic GVHD.
authors.affiliation: University of California, Davis 95616-8660, USA.
authors.forename: S
authors.initials: S
authors.lastname: Quaranta
authors.forename: H
authors.initials: H
authors.lastname: Shulman
authors.forename: A
authors.initials: A
authors.lastname: Ahmed
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
authors.forename: J
authors.initials: J
authors.lastname: Peter
authors.forename: G B
authors.initials: GB
authors.lastname: McDonald
authors.forename: J
authors.initials: J
authors.lastname: Van de Water
authors.forename: R
authors.initials: R
authors.lastname: Coppel
authors.forename: C
authors.initials: C
authors.lastname: Ostlund
authors.forename: H J
authors.initials: HJ
authors.lastname: Worman
authors.forename: M
authors.initials: M
authors.lastname: Rizzetto
authors.forename: K
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Y
authors.initials: Y
authors.lastname: Nakanuma
authors.forename: A
authors.initials: A
authors.lastname: Ansari
authors.forename: F
authors.initials: F
authors.lastname: Locatelli
authors.forename: S
authors.initials: S
authors.lastname: Paganin
authors.forename: F
authors.initials: F
authors.lastname: Rosina
authors.forename: M
authors.initials: M
authors.lastname: Manns
authors.forename: M E
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D000328:Adult; D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens; D016022:Case-Control Studies; D002417:Cattle; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000209:etiology / Q000276:immunology / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000276:immunology; D009130:Muscle, Smooth / Q000276:immunology
chemical_list: D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens