Autoimmunity in Liver Disease
Primary biliary cirrhosis (PBC)
Presentation
PBC is a disease of older women (90% of patients are female).
Clinical features include initially:
profound fatigue starting in the prodrome
intense itch
arthralgia.
With disease progression:
hepatosplenomegaly
xanthelasma
skin pigmentation
eventually hepatic decompensation with jaundice.
The disease is strongly associated with other autoimmune diseases,
ncluding Sjögren’s syndrome, thyroid disease, cryptogenic fibrosing alveolitis, CREST (calcinosis, Raynaud’s, oesophageal dysmotility, sclerodactyly, and telangiectasia), and renal tubular acidosis.
Other autoimmune diseases (any type) occur more rarely.
Immunogenetics
No specific genetic linkages identified (familial occurrence is uncommon).
Cause unknown, but epidemiological work on clusters of disease suggests a possible infectious aetiology.
It is particularly common in the northeast of England.
Immunopathology
Not strictly a cirrhotic disease, as the primary pathology is inflammation around the portal triads (intrahepatic bile ducts), leading eventually to fibrosis.
Occasional overlap patients occur with features of PBC and also of chronic autoimmune hepatitis.
Increased HLA-DR expression on the biliary epithelium and an infiltrate of CD4+ T cells specific for biliary epithelial antigens.
An excess of IgM-producing B cells is seen around the biliary ducts.
Diagnosis (see Box 8.1)
LFTs show elevated alkaline phosphatase. Caeruloplasmin, lipoproteins, and cholesterol are also raised.
Biopsy shows typical features.
Total IgM levels are polyclonally raised, often significantly (20-30g/L), although the reason for this is not known.
Occasionally small monoclonal bands will be seen on electrophoresis.
Autoantibodies are diagnostic.
Box 8.1 Testing for primary biliary cirrhosis
|
Autoantibodies
Typical immunological features are the presence of mitochondrial antibodies, found in 96% of cases.
A variety of different mitochondrial antibody patterns are identifiable (with difficulty!) by immunofluorescence (see Chapter 18 for descriptions).
The M2 pattern is most commonly associated with PBC.
M2 autoantigens have now been identified as trypsin-sensitive molecules on the inner mitochondrial membrane.
Primary antigen is the large multimeric 2-oxo-acid dehydrogenase complex, pyruvate dehydrogenase complex (PDC).
M2c recognizes the E2 antigen of oxoglutarate dehydrogenase (OGDC) (39-88% of PBC) and branch-chain 2-oxo-acid dehydrogenase (BCOADC) (54%), and the protein × component of PDC (95%).
M2d and M2e antigens are the E1-α and E1-β? components of PDC (41-66% and 2-7%, respectively).
Solid-phase assays are available for M2 antigens and should be used to confirm the specificity of antibodies identified by immunofluorescence.
Antibodies recognize conserved epitopes on related proteins found in fungi and bacteria.
Antibodies, which are mainly IgM and IgG3, are known to inhibit enzyme function and may penetrate viable cells.
Other antibodies have been thought to identify subgroups of PBC.
M9 antibody (anti-glycogen phosphorylase) may be a marker for early PBC with a benign prognosis (also found in low titres in healthy individuals).
M4 antibody may be a marker of aggressive disease (anti-sulphite oxidase).
Non-M2 anti-mitochondrial antibodies (AMAs) are found in myocarditis, SLE, syphilis, and some drug reactions.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
