Pbc and Ama—What Is the Connection?

Abstract

Primary Biliary Cirrhosis (PBC) is very closely associated with the presence of antimitochondrial antibodies (AMA); indeed, the presence of these antibodies is virtually disease specific. Despite the major advances made during the last decade in identifying the antigens with which these antibodies react, the reason for the close association remains uncertain. In this review, we examine the clinical correlates of AMA with features of PBC and discuss the possible implications of the association. CLINICAL CORRELATES Epidemiology of PBCThere is geographical variation in the prevalence of PBC, being highest in areas such as the north of England and parts of North America but rare in Africa and the Indian subcontinent. 1 Studies from the north of England suggest that the incidence of PBC is increasing. Clustering of cases is well described. 2 PBC may occur in families, and up to 4% of first-degree relatives may have PBC. Where PBC does occur in families, it may be related to maternally inherited factors and tends to present earlier in the second generation. 3 AMA Are Detectable Before the Clinical and Histological Features of PBCOf 29 asymptomatic patients who were found to have AMA in serum (later confirmed to be reactive with E2 components of pyruvate dehydrogenase) but with normal liver tests only two had normal liver histology. 4 A decade later, 76% had developed symptoms of PBC and 83% had cholestatic liver tests. None had progressed to cirrhosis. 5

Primary biliary cirrhosis: New thoughts on pathophysiology and treatment

“…In one clinical trial with ursodeoxycholic acid (UDCA), the improvement in liver function tests corresponded with a reduction in AMA titers [6]. Otherwise, AMA do not appear to have an obvious correlation with the disease process, because PBC patients without detectable AMA have a disease process that is comparable with the process of those who have detectable AMA, AMA titers do not correlate with disease activity, and some AMA-positive individuals have no disease at all [7]. Although reduced AMA levels coincide with improved hepatic biochemistry studies in UDCA treatment, there is little to suggest a causal role for autoimmunity in PBC.…”

New ELISA for Detecting Primary Biliary Cirrhosis–Specific Antimitochondrial Antibodies

“…Moreover, approximately 5% of well-documented PBC patients are negative for AMAs by IFL and do not react with any of the PDC-based preparations (18,20 ). These findings have raised questions as to whether AMA-negative PBC cases represent a distinct patient population or simply have AMA titers and specificities not detectable with the conventional IFL and molecular-based assays (9,13,(21)(22)(23). Thus, attempts have been made in the recent past to develop in-house ELISAs based on antigenic mixtures (13,24 ) or a hybrid containing the immunodominant PDC-E2, BCOADC-E2, and OGDC-E2 epitopes, designated as MIT3 (because it contains the 3 major mitochondrial epitopes) (23 ) or BPO (from the abbreviations BCOADC, PDC, and OGDC) (25 ).…”

Editorial: Recurrent primary biliary cirrhosis

“…11 What can the lessons of transplantation for PBC tell us about the disease and its treatment? Although controversy remains about some of the observations regarding recurrent PBC, there are some strands of agreement.…”