Antinuclear Antibodies in Primary Biliary Cirrhosis

Abstract

Patients with primary biliary cirrhosis (PBC) generate a variety of autoantibodies, which are primarily directed against mitochondrial antigens (AMA). However, a subgroup of patient sera are also positive for antibodies to nuclear components (ANAs). At indirect immunofluorescence (IIF), PBC sera mostly produce homogeneous, nuclear dot, speckled, centromere, or rim-like patterns. During the last two decades, a number of nuclear structures have been recognized as specific targets of ANA in PBC. These include Sp100 and promyelocytic leukemia proteins, which generate a nuclear dot IIF pattern, and two components of the nuclear pore complex specifically associated with a perinuclear pattern (i.e., gp210 and p62). In recent years, the clinical significance of ANA in PBC has been widely investigated and data indicate that, unlike AMAs, PBC-specific ANAs correlate with disease severity and may therefore be a marker of poor prognosis.

Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation

“…Group 2 S.i-inoculated BALB/c mice also produced antinuclear antibodies (ANAs), as shown by staining using HEp2 cells (Figure 7d, A), whereas, in the Group 1 S.i.-inoculated BALB/c mice, the titers for ANAs seemed to be much lower than those in Group 2 (Figure 7d, B). As antigp210 antibodies have been detected in patients with PBC, 4,24 anti-gp210 reactivity was measured using an ELISA. When the OD value exceeded the mean OD value of the Group 2 PBS-injected mice þ 3 s.d., we defined the sample as being positive for anti-gp210 antibody induction.…”

“…Primary biliary cirrhosis (PBC), a slowly progressive autoimmune disease of the liver, is characterized by immune-mediated portal inflammation and destruction of the intrahepatic bile ducts and serologically by the presence of anti-mitochondrial antibodies (AMAs) 2,3 and anti-gp210. 4 As for coexisting autoimmune tissue damage characterized by multifocal epithelial inflammation, Sjögren's syndrome, hypothyroidism, renal tubular acidosis, and other conditions have been reported. 2 Although the pathogenesis of biliary epithelial cell damage in PBC is still not clearly understood, molecular mimicry has been proposed as a possible mechanism.…”

Clinicopathological Significance of Serum Fractalkine in Primary Biliary Cirrhosis

“…Although a serological hallmark of PBC is the presence of AMA, which is found in >90% of patients, ANAs are also detected in PBC patients [13][14][15][16][17]. Anti-gp210 and anti-sp100 antibodies are highly specific for PBC and useful for its diagnosis, particularly those who are negative for AMAs [13][14][15][16][17].…”

“…Anti-gp210 and anti-sp100 antibodies are highly specific for PBC and useful for its diagnosis, particularly those who are negative for AMAs [13][14][15][16][17]. In addition, although AMAs are not associated with disease progression, ANAs are associated with disease severity and are therefore useful as a marker of poor prognosis [15][16][17][18].…”

Experimental evidence on the immunopathogenesis of primary biliary cirrhosis

“…Multiple nuclear dots reactivity is based on the recognition of Sp100 and promyelocytic leukemia proteins (possibly also crossreacting with small ubiquitinlike modifiers). 73 Rim-like reactivity reacts against proteins of the nuclear pore complexes (NPCs) that include gp210 (a 210-kDa transmembrane glycoprotein involved in the attachment of NPC constituents within the nuclear membrane), nucleoporin p62 (a glycoprotein located in the core of NPCs) and the inner nuclear membrane protein lamin B receptor. Serum anti-gp210 antibodies are detected in about 25% of patients with PBC (range: 10-40%), while anti-p62 and antilamin B receptor antibodies are found in about 13 and 1%, respectively.…”