Late-Onset Autoimmunity: The Paradigm of Primary Biliary Cirrhosis – A Mini-Review

Abstract

The incidence of autoimmune diseases appears to be increasing in virtually every population. This is well illustrated by primary biliary cirrhosis, a disease characterized by an immune response to small bile ducts and an incidence increasing with age. The etiology of primary biliary cirrhosis remains enigmatic, although there is clearly an interplay of genetics and environment with a possible role for immunosenescence. The increasing usage of serologic tests for the hallmark of primary biliary cirrhosis, the antimitochondrial antibody, has dramatically changed the spectrum of disease presentation and natural history. In the past, data were predominantly based on the greater prevalence of advanced cases, whereas now most patients are detected earlier through the use of multi-phasic chemistry panels. In this review, we will place the epidemiology of primary biliary cirrhosis in the context of its clinical features and treatment as well as emphasize the future directions to further understand the immunobiology of this disease.

The Immunology of Fibrosis

“…In autoimmune hepatitis, these are α-smooth muscle actin, liver kidney microsomal antigens, and soluble liver/liver pancreas-or liver-cytosol-specific antigens (102). In primary biliary cirrhosis, the multienzyme 2-Oxo-acid dehydrogenase complex contains the culprit autoantigens (103).…”

Liver disorders in the elderly

“…The age at presentation in the last years is around 60 years, but many patients are over 65 at onset of the disease [63]. Several prognostic models for PBC have confirmed that increasing age does have an independent and adverse effect on prognosis [64], implying that the natural history in elderly subjects may be worse.…”

Unravelling autoimmune pathogenesis by screening random peptide libraries with human sera

“…Primary biliary chirrosis (PBC) [77] and autoimmune cholangitis (AIC) are autoimmune liver diseases affecting biliary ductular cells. In predicting the immunodominant epitope of the pyruvate dehydrogenase complex E2 in PBC [78], phagotopes were selected from RPLs with PBC sera and shown to be reactive by capture ELISA with antibodies affinity purified on the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2) [79].…”