A 45-year-old woman with autoimmune hepatitis is found to have serum anti-SLA/LP antibody positivity (anti-soluble liver antigen/liver-pancreas). She is also ANA positive and anti-smooth muscle antibody positive. Which gene product is the target of anti-SLA/LP antibody and what is its clinical significance?
- A UGA suppressor tRNA-associated protein (SEPSECS/SepSecS) — anti-SLA/LP is highly specific for autoimmune hepatitis and associated with severe disease, risk of relapse, and need for long-term immunosuppression ✓
- B Cytochrome P450 2D6 (CYP2D6) — also targeted by anti-LKM-1 antibodies in AIH type 2
- C LC-1 (liver cytosol antigen type 1) — formiminotransferase cyclodeaminase; associated with AIH type 2 in overlap with PBC
- D Mitochondrial M2 antigen (pyruvate dehydrogenase complex E2) — the target of AMA antibodies in primary biliary cholangitis
Explanation
Anti-SLA/LP (anti-soluble liver antigen/liver-pancreas) antibodies target SepSecS (selenocysteine tRNA synthase/UGA suppressor tRNA-associated protein), a cytoplasmic enzyme involved in selenoprotein synthesis. Anti-SLA/LP is highly specific (>99%) for autoimmune hepatitis and is associated with HLA-DRB1*0301, a severe and relapsing disease course, and requirement for long-term immunosuppression. It defines a subset that may be seronegative for ANA/ASMA in some cases. Anti-LKM-1 targets CYP2D6 and defines AIH type 2; anti-LC-1 targets FTCD in AIH type 2 (young patients with concurrent HCV); anti-AMA (anti-M2) targets PDC-E2 in primary biliary cholangitis.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.