Aim: D-3-phosphoglycerate dehydrogenase (3-PHGDH) was identified as a putative target of autoantibodies in autoimmune hepatitis (AIH). The aims of the present study were to detect anti-3-PHGDH in patients with AIH and other chronic liver diseases and to analyze their clinical relevance.
Methods: Human 3-PHGDH gene was cloned and expressed in Escherichia coli and used in enzyme-linked immunosorbent assays and Western blots. Serum from patients with AIH (n = 101), primary biliary cirrhosis (PBC, n = 122), chronic hepatitis C (CHC, n = 117), chronic hepatitis B (CHB, n = 112), and from patients with other autoimmune disease (n = 125) were investigated.
Results: The highest incidence and activity of anti-PHGDH was observed in AIH patients. Thirty-two of 40 untreated (80%) and 37 of 61 AIH patients treated with corticosteroid (60.7%) were positive. Antibody titers decreased significantly during corticosteroid treatment. 15.8% of PBC patients, 9.8% of CHB and 12.8% of CHC patients, were anti-PHGDH-positive, with less than 12% of patients positive with other autoimmune diseases via reactions with recombinant 3-PHGDH protein.
Conclusion: Anti-PHGDH were detected in chronic liver diseases. They occur predominantly in AIH, and corticosteroid treatment seems to decrease antibody titers. Whether the antibodies are primary or secondary phenomena and whether they are related to the etiology or pathogenesis, at least in a subgroup of patients with chronic liver diseases, has still to be evaluated.