Evolving Concepts in Primary Sclerosing Cholangitis
Evolving Concepts in Primary Sclerosing Cholangitis
Antineutrophil cytoplasmatic antibodies (ANCA) are a heterogeneous group of autoantibodies against cellular components of leucocytes. ANCA in PSC, AIH and UC mainly produce an 'atypical' perinuclear fluorescence pattern ('atypical' pANCA) with staining of the nuclear periphery and intranuclear fluorescent foci. This pANCA subtype in PSC occurs in 29–94%. High prevalence of pANCA in PSC with coexisting IBD has been reported. Whether pANCA also occur in small duct PSC has not yet been investigated. As pANCA can also be found in AIH and UC, specificity in establishing diagnosis of PSC is low and routine testing is not recommended. Besides ANCA of IgG class, ANCA of IgA class have been reported in up to 55% of PSC patients. Furthermore, IgA class ANCA were found in 28–52% of patients with UC, suggesting involvement of the gut-associated lymphoid tissue (GALT) in ANCA production. However, IgA class ANCA are significantly more prevalent in AIH than in PSC patients but their overall prevalence is significantly lower compared with IgG class ANCA. No association has been reported between the presence of IgA class ANCA and clinical characteristics of PSC and AIH. An antibody against human tropomyosin isoform 5 (hTM5) – a 40 kDa antigenetic protein expressed in colonic and biliary epithelium – has been found in PSC but its diagnostic relevance remains uncertain. Antibodies against biliary epithelial cells inducing expression of IL-6, CD44 and Toll-like receptors could be isolated from sera of PSC and PBC patients with undefined clinical relevance. In addition, low specificity was reported for ANA, SMA, anti-endothelial cell antibody, anti-cardiolipin antibody, thyroperoxidase, thyroglobulin and rheumatoid factor in PSC. Taken together, routine autoantibody testing has no role as standard diagnostic test in PSC.
What is the Value of Antibody Testing in PSC?
Antineutrophil cytoplasmatic antibodies (ANCA) are a heterogeneous group of autoantibodies against cellular components of leucocytes. ANCA in PSC, AIH and UC mainly produce an 'atypical' perinuclear fluorescence pattern ('atypical' pANCA) with staining of the nuclear periphery and intranuclear fluorescent foci. This pANCA subtype in PSC occurs in 29–94%. High prevalence of pANCA in PSC with coexisting IBD has been reported. Whether pANCA also occur in small duct PSC has not yet been investigated. As pANCA can also be found in AIH and UC, specificity in establishing diagnosis of PSC is low and routine testing is not recommended. Besides ANCA of IgG class, ANCA of IgA class have been reported in up to 55% of PSC patients. Furthermore, IgA class ANCA were found in 28–52% of patients with UC, suggesting involvement of the gut-associated lymphoid tissue (GALT) in ANCA production. However, IgA class ANCA are significantly more prevalent in AIH than in PSC patients but their overall prevalence is significantly lower compared with IgG class ANCA. No association has been reported between the presence of IgA class ANCA and clinical characteristics of PSC and AIH. An antibody against human tropomyosin isoform 5 (hTM5) – a 40 kDa antigenetic protein expressed in colonic and biliary epithelium – has been found in PSC but its diagnostic relevance remains uncertain. Antibodies against biliary epithelial cells inducing expression of IL-6, CD44 and Toll-like receptors could be isolated from sera of PSC and PBC patients with undefined clinical relevance. In addition, low specificity was reported for ANA, SMA, anti-endothelial cell antibody, anti-cardiolipin antibody, thyroperoxidase, thyroglobulin and rheumatoid factor in PSC. Taken together, routine autoantibody testing has no role as standard diagnostic test in PSC.
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