Prevalence, kinetics, and therapeutic modulation of autoantibodies against Sp100 and promyelocytic leukemia protein in a large cohort of patients with primary biliary cirrhosis.
Antinuclear antibodies (ANA) staining nuclear dot structures predominantly occur in primary biliary cirrhosis (PBC) patients and recognize the Sp100 and promyelocytic leukemia protein (PML). From retrospective analysis of sera from a clinically well-defined Canadian series of 170 PBC patients included into a 24-month therapeutic trial of ursodeoxycholic acid (UDCA), we report the prevalence of these ANA and their dynamics in the course of the disease. Using an enzyme-linked immunosorbent assay (ELISA), anti-Sp100 autoantibodies were shown in 35 (21%) patients. Thirty-three patients (19%) had autoantibodies against PML as determined by indirect immunostaining of cells overexpressing PML. Altogether, anti-nuclear dot autoantibodies were present in 25% of the 170 PBC patients. Their occurrence correlated with an unfavorable disease course, because these patients progressed significantly more frequently from early stages (I/II) to late stages (III/IV) within the 24-month observation period (P < .05). During the course of the disease, the autoantibody levels against the Sp100 full-length protein remained nearly constant in all 35 positive patients. However, 9 patients showed remarkable changes in Sp100 epitope recognition as revealed by ELISA and immunoblotting. When the occurrence of these changes and the treatment of the patients were compared retrospectively, it became evident that 8 of the 9 patients had received UDCA (42% of all Sp100-positive patients treated with UDCA). These findings indicate subtle changes of the Sp100 epitope recognition pattern during the natural course of the disease and its induction or acceleration by UDCA treatment. This implies that UDCA can modulate immunoglobulin (Ig) expression not only quantitatively, but also qualitatively.
Züchner
D
D
Heinrich-Pette-Institut für experimentelle Virologie und Immunologie an der Universität Hamburg, Germany.
Sternsdorf
T
T
Szostecki
C
C
Heathcote
E J
EJ
Cauch-Dudek
K
K
Will
H
H
D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D002467:Cell Nucleus / Q000276:immunology; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D009687:Nuclear Proteins / Q000276:immunology*; D015388:Organelles / Q000276:immunology; D015995:Prevalence
D034961:Antigens, Nuclear; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C066642:SP100 protein, human