Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis

Abstract

Although there have been significant advances in understanding the clinical and biochemical features of primary biliary cirrhosis (PBC), there is still a paucity of data on the usefulness of biomarkers as prognostic indicators. This is particularly important at the time of initial diagnosis. Indeed, the widespread use of antimitochondrial antibody testing has led to an earlier diagnosis of asymptomatic PBC and it is difficult to predict which patients will experience a benign versus a rapidly progressive course. To address this issue, we examined a unique population of 127 newly diagnosed patients with PBC during a 15-year period of observation that began in January 1990. Sera from these patients were analyzed for antimitochondrial, antinuclear, and anti-smooth muscle antibodies, and immunoblotting was performed for nuclear pore complex (NPC). The patients were then followed up longitudinally using biochemical liver function tests. No patient was under any medical therapy for PBC at the time of the initial sera collection. Data were analyzed based not only on the clinical features, but also the Mayo score and specific outcome measures, including time to death, need for liver transplantation, and complication free survival. Among patients with early disease, bilirubin increased to >2 mg/dL in the anti-NPC(؉) patients (26% vs. 5%, P ‫؍‬ .019). Anti-NPC antibodies remained stable or slightly increased over the period of observation. In conclusion, anti-NPC identifies patients likely to experience an unfavorable clinical course and more rapid disease progression. (HEPATOLOGY 2006;43:1135-1144

Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis

“…[22][23][24][25] However, this finding needs to be validated in larger longitudinal studies. Sp100 and gp210 proteins are the main antigenic targets of anti-ND and anti-nuclear pore complex antibodies, respectively.…”

Single-nucleotide polymorphism analysis of the multidrug resistance protein 3 gene for the detection of clinical progression in Japanese patients with primary biliary cirrhosis

“…5,6 However, this marker is not associated with progression of PBC. [5][6][7][8][9][10] Furthermore, antinuclear antibodies are also specifically detected in approximately 50% of PBC patients. 5,6,11 Because anti-gp210 and anti-sp100 antibodies are highly specific for PBC and are associated with disease severity, these autoantibodies are good biomarkers not only for making a diagnosis, but also for predicting both the prognosis and severity of PBC.…”

“…5,6,11 Because anti-gp210 and anti-sp100 antibodies are highly specific for PBC and are associated with disease severity, these autoantibodies are good biomarkers not only for making a diagnosis, but also for predicting both the prognosis and severity of PBC. [5][6][7][8][9][10][11] PBC is a multifactorial disorder in which both multiple genetic and environmental factors may contribute to the etiology. 1,2,12 Unknown genetic factors predominantly determine the disease susceptibility, onset, and progression of PBC, because the concordance rate of PBC in monozygotic twins is 63%, 13 compared with 12% in rheumatoid arthritis, 14 and familial PBC is reported at variable frequency rates, 12,15 including 5.1% in Japan, 16 as calculated by the number of unrelated index PBC cases.…”

Reply:

“…2 We have reason to believe that the actual target was mouse Reg3␤ (also known as Reg III␤; or PAP, PAP1 and HIP in other species). [3][4][5] As shown in Fig. 1, the polymerase chain reaction (PCR) primers used to genotype the knockout offspring were perfectly matched to the genomic sequence of mouse Reg3␤ gene (access number D63360), which would generate a product of 687 base pairs, similar to the 600 base pairs reported.…”