Autoantibodies to human cytosol: a marker of sporadic porphyria cutanea tarda

The enzymes potentially involved in the pathogenesis of sporadic porphyria cutanea tarda (PCT) reside in liver cytosoles and microsomes. PCT is freque ntly associated with hepatitis C virus (HCV) infection, which is in turn as sociated with autoimmune manifestations. To investigate whether autoimmune reactions, possibly triggered by HCV, are involved in the pathogenesis of P CT, we measured by immunoblot autoantibodies to human cytosolic and microso mal liver fractions in 82 patients with PCT (77% with HCV infection), 105 w ith other liver disorders and 40 healthy subjects. Anti-liver cytosolic ant ibodies were more frequent in PCT patients (38/82, 46%) than in pathologica l controls (P < 0.05-P < 0.001) or in healthy subjects (3/40, 8%, P < 0.001 ). Among PCT patients, anticytosolic antibodies were more frequent in HCV p ositive (36/63, 57%) than in HCV negative (2/19, 11%, P < 0.05) cases. Reac tivity to a 40-kDa cytosolic polypeptide was present in 20 PCT patients (19 HCV positive), being more frequent than in all pathological controls (P < 0.01-P < 0.0001). Histological activity index (P = 0.04) and antibodies to HCV (P = 0.027) - but not HCV RNA - were associated independently with anti cytosolic antibodies as assessed by multivariate analysis. In contrast, fre quency of antiliver microsomal antibodies was similar in PCT patients (24/8 2, 29%) and pathological controls (8-26%), being higher in the autoimmune h epatitis control group (23/23, 100%, P < 0.0001). In conclusion, anticytoso lic antibodies, particularly to a 40-kDa polypeptide, are frequent in PCT a nd associated with HCV infection and severity of liver damage.