cathepsin-g and Hepatitis--Autoimmune

Anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 are diagnostic of Wegener's granulomatosis, but ANCA occur also in patients with other inflammatory disorders, such as ulcerative colitis, primary sclerosing cholangitis (PSC) and autoimmune hepatitis. As their predictive value for autoimmune liver disease remains unknown, we analysed the prevalence and antigen specificity of ANCA in patients with various chronic liver diseases (CLD).. We studied sera from 100 patients with primary biliary cirrhosis (PBC), from 76 with PSC and from 279 with various CLD, consecutively drawn during a 5-year period at the time of liver biopsy. The ANCA were detected by indirect immunofluorescence (IIF) while the antigen specificity was characterized by ELISA by using lactoferrin, neutrophil elastase, cathepsin G and BPI (bactericidal/permeability increasing protein) as antigens.. In PBC, ANCA were detected by IIF in 39 patients (39%). The antigen reactivity by ELISA was lactoferrin in seven, elastase in 15, BPI in 20 and cathepsin G in four patients. Four patients had reactivity against more than one antigen. In PSC, IIF demonstrated ANCA in 49 patients (65%). The antigen reactivity was lactoferrin in 17, elastase in 14, BPI in 20 and cathepsin G in four patients. Twelve patients showed reactivity against more than one antigen. In CLD, ANCA were observed in sera from 55 patients (20%). Nineteen of 45 patients (42%) with autoimmune liver disease were ANCA positive versus 36/234 (15%) with non-autoimmune liver disease (P = 0.0002). Among IIF-positive patients, antibody reactivity against lactoferrin was noted in 14, elastase in 28, BPI in 25 and cathepsin G in five patients. Twenty-one patients had reactivity against more than one antigen. Elastase and BPI antibodies occurred more frequently in patients with autoimmune compared to non-autoimmune liver disease (P < 0.01).. Anti-neutrophil cytoplasmic antibodies are prevalent in patients with chronic liver diseases, but although they occur more frequently in patients with autoimmune liver disease their specificity and sensitivity for autoimmune liver disease is low. The predominant antigens are lactoferrin, elastase and BPI, but the correlation between IIF findings and ELISA reactivity against these antigens is weak.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antimicrobial Cationic Peptides; Autoantigens; Biomarkers; Blood Proteins; Cathepsin G; Cathepsins; Cholangitis, Sclerosing; Enzyme-Linked Immunosorbent Assay; Epitopes; Fluorescent Antibody Technique, Indirect; Hepatitis, Autoimmune; Humans; Lactoferrin; Leukocyte Elastase; Liver Cirrhosis, Biliary; Membrane Proteins; Myeloblastin; Prognosis; Sensitivity and Specificity; Serine Endopeptidases

High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 have been identified as novel antigens of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCAs), and the existence of anti-HMG1 and anti-HMG2 antibodies in a population of patients with ulcerative colitis has been reported.. To investigate whether HMG1 and HMG2 are target antigens for p-ANCAs in autoimmune hepatitis (AIH).. Serum samples from 28 patients with AIH, 44 patients with primary biliary cirrhosis (PBC), 27 patients with chronic hepatitis C, and 23 patients with chronic hepatitis B were tested.. ANCAs were detected by routine indirect immunofluorescence (IIF). Anti-HMG1 and anti-HMG2 antibodies were assayed by enzyme linked immunosorbent assay.. p-ANCAs were detected in 89% (25/28) of patients with AIH, 36% (16/44) of patients with PBC, 11% (3/27) of patients with chronic hepatitis C, and 13% (3/23) of patients with chronic hepatitis B. Anti-HMG1 and/or anti-HMG2 antibodies were detected in 89% (25/28) of patients with AIH, 70% (31/44) with PBC, 26% (7/27) with chronic hepatitis C, and 9% (2/23) with chronic hepatitis B. In AIH, anti-HMG1 and/or anti-HMG2 antibodies were detected in 96% (24/25) of p-ANCA positive patients. The p-ANCA staining pattern detected by IIF using sera from patients with AIH disappeared or decreased in titre after preincubation with a mixture of HMG1/HMG2. The presence and titres of those antibodies in AIH correlated significantly with those of p-ANCA, but not with those of anti-nuclear antibody or anti-smooth muscle antibody.. HMG1 and HMG2 are significant target antigens of p-ANCA in AIH.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Cathepsin G; Cathepsins; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Hepatitis B, Chronic; Hepatitis C, Chronic; Hepatitis, Autoimmune; High Mobility Group Proteins; Humans; Lactoferrin; Liver Cirrhosis, Biliary; Male; Middle Aged; Serine Endopeptidases; Statistics, Nonparametric