dsDNA were shown in 64% of patients with autoimmune To determine the significance of antibodies to singlehepatitis, 46% with cryptogenic hepatitis, and 43% with stranded (anti-ssDNA) and double-stranded DNA (antichronic hepatitis B. 8 Tsuchiya and colleagues, using an ELISA dsDNA) in antinuclear antibody (ANA)-positive type 1 autobased on a similar substrate, found anti-dsDNA in 48% of immune hepatitis, sera from 53 patients were tested by patients with autoimmune hepatitis and 17% of patients with enzyme immunosorbent assay (ELISA) and indirect immunoprimary biliary cirrhosis. 9 Testing of the same sera by an fluorescence using the Crithidia luciliae substrate. Antiindirect immunofluorescence assay based on the kinetoplast dsDNA were detected in 18 patients (34%) by ELISA and 12
of Crithidia luciliae, a pure source of dsDNA, disclosed simipatients (23%) by the Crithidia-based assay. Twenty patients lar results. 9 A smaller study from Australia, using an immuwith anti-dsDNA by either assay (38%) had higher serum nofluorescence assay based on Crithidia luciliae, also showed levels of immunoglobulin G (3971 { 270 mg/dL vs. 3201 { a significant serologic overlap with SLE. 10 247 mg/dL, P Å .05) than seronegative patients. They also Methodological differences can affect the detection of antihad human leukocyte antigen (HLA) DR4 more commonly dsDNA and the assessment of its clinical significance. Conthan other patients (83% vs. 41%, P Å .006) and normal tamination of the dsDNA substrate with single-stranded DNA subjects (83% vs. 30%, P Å .00007). In contrast to patients (ssDNA) may result in false positive results in some inseropositive by the Crithidia-based assay, those seropositive stances. 5 Differences in antibody avidity and class may also by ELISA failed corticosteroid therapy more commonly (24% influence detection. ELISAs detect antibodies of low avidity vs. 3%, P Å .04). Anti-ssDNA were found in 45 patients that may predominate in diseases other than SLE whereas (85%) and they did not distinguish patients with different the Crithidia assay may detect only high avidity antibodies clinical features or outcomes. We conclude that anti-dsDNA of greater pathogenic importance. 11 are common in ANA-positive type 1 autoimmune hepatitis.
In this report, we determine the concordance of tests for HLA DR4 is associated with their production, and seroposianti-dsDNA by an ELISA and a Crithidia-based assay in pativity by ELISA characterizes patients who have a poorer tients with well-characterized antinuclear antibody (ANA)immediate response to corticosteroid treatment. Anti-ssDNA positive type 1 autoimmune hepatitis. We correlate seroare common but they do not have important clinical implicapositivity by each assay to clinical features and treatment tions. (HEPATOLOGY 1997;26:567-572.) outcome to determine the clinical pertinence of the findings and we evaluate the association between antibody expression Antibodies to double-stranded DNA (anti-dsDNA) have a and the known genetic risk factors for type 1 autoimmune high specificity for the diagnosis of systemic lupus erythemahepatitis. We also determine the frequency of antibodies to tosus (SLE) and they correlate closely with disease activity. [1][2][3][4][5][6][7] ssDNA (anti-ssDNA) to evaluate further the clinical relevance Nonrheumatic diseases, including autoimmune hepatitis, of anti-dsDNA. may also have anti-dsDNA and the specificity of these antibodies for SLE has been challenged. [8][9][10]
PATIENTS AND METHODS
In our earlier experience using an enzyme-linked immuno-Study Population. Fifty-three patients were selected for further sorbent assay (ELISA) and highly purified dsDNA, antistudy from the 303 patients entered in our chronic hepatitis treat- ment program. Patients were selected because: 1) each satisfied international criteria for autoimmune hepatitis; 12 2) each had ANA in serum that justified their designation as ANA-positive type 1 Abbreviations: Anti-dsDNA, antibodies to double-stranded DNA; SLE, systemic autoimmune hepatitis; 13 3) each had been screened and seronegalupus erythematosus; ELISA, enzyme-linked immunosorbent assay; ssDNA, singletive for serological markers of hepatitis B and C virus infection by stranded DNA; ANA, antinuclear antibodies; anti-ssDNA, antibodies to single-stranded second generation assays; 4) none satisfied the criteria of the Ameri-DNA; SMA, smooth muscle antibody; PBS, phosphate buffered saline; IU, international unit; HLA, human leukocyte antigens.