Antibodies to soluble liver antigen/liver pancreas and HLA risk factors for type 1 autoimmune hepatitis.
OBJECTIVE
Antibodies to soluble liver antigen/liver-pancreas are highly specific markers of type 1 autoimmune hepatitis that have been associated with relapse. Our aim was to determine if these antibodies are reflective of a genetic predisposition for recrudescent disease.


METHODS
One hundred forty-four white North American patients were evaluated by an enzyme immunoassay and by Western blot using recombinant soluble liver antigen/liver-pancreas; 122 were assessed for class II human leukocyte antigens (HLAs).


RESULTS
Twenty-two patients (15%) had antibodies to soluble liver antigen/liver-pancreas. These patients were indistinguishable from seronegative patients by clinical, laboratory, and histological features at presentation. Patients with antibodies to soluble liver antigen/liver pancreas had HLA DR3 (79% vs 50%, p = 0.02) more commonly and HLA DR4 less often (16% vs 47%, p = 0.02) than patients with smooth muscle antibodies and/or antinuclear antibodies. Seropositivity was associated with DRB1*0301 and seronegativity was associated with DRB1*0401. Relapse after drug withdrawal occurred in all patients with antibodies to soluble liver antigen/liver-pancreas and at a higher frequency than in patients with conventional antibodies (100% vs 78%, p = 0.05).


CONCLUSIONS
Antibodies to soluble liver antigen/liver pancreas are associated with HLA DR3 and the susceptibility allele, DRB1*0301. Antibodies to soluble liver antigen/liver-pancreas may be surrogate markers of a genetic propensity for recrudescent disease or the target autoantigen. They may be complementary to antinuclear antibodies and smooth muscle antibodies in diagnosis and management.
Czaja
Albert J
AJ
Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Donaldson
Peter T
PT
Lohse
Ansgar W
AW
D000328:Adult; D000974:Antibodies, Antinuclear / Q000032:analysis* / Q000276:immunology; D001324:Autoantigens / Q000032:analysis* / Q000276:immunology; D015153:Blotting, Western; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015803:HLA-DR3 Antigen / Q000032:analysis* / Q000276:immunology; D015804:HLA-DR4 Antigen / Q000032:analysis* / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010182:Pancreatic Diseases / Q000276:immunology; D011336:Probability; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012995:Solubility; D018709:Statistics, Nonparametric
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; C046431:liver antigen LA-1