Autoantibodies to human cytosol: a marker of sporadic porphyria cutanea tarda
Y. Ma
Institute of Hepatology, University College London and University College London Hospitals,
Search for more papers by this authorA. L. Fracanzani
Dipartimento di Medicina Interna, IRCCS Ospedale Maggiore, Milano, Italy
Search for more papers by this authorM. Sampietro
Dipartimento di Medicina Interna, IRCCS Ospedale Maggiore, Milano, Italy
Search for more papers by this authorM. Mattioli
Dipartimento di Medicina Interna, IRCCS Ospedale Maggiore, Milano, Italy
Search for more papers by this authorP. Cheeseman
Department of Child Health, King’s College Hospital, London, UK, and
Search for more papers by this authorR. Williams
Institute of Hepatology, University College London and University College London Hospitals,
Search for more papers by this authorG. Mieli-Vergani
Department of Child Health, King’s College Hospital, London, UK, and
Search for more papers by this authorD. Vergani
Institute of Hepatology, University College London and University College London Hospitals,
Search for more papers by this authorS. Fargion
Dipartimento di Medicina Interna, IRCCS Ospedale Maggiore, Milano, Italy
Search for more papers by this authorY. Ma
Institute of Hepatology, University College London and University College London Hospitals,
Search for more papers by this authorA. L. Fracanzani
Dipartimento di Medicina Interna, IRCCS Ospedale Maggiore, Milano, Italy
Search for more papers by this authorM. Sampietro
Dipartimento di Medicina Interna, IRCCS Ospedale Maggiore, Milano, Italy
Search for more papers by this authorM. Mattioli
Dipartimento di Medicina Interna, IRCCS Ospedale Maggiore, Milano, Italy
Search for more papers by this authorP. Cheeseman
Department of Child Health, King’s College Hospital, London, UK, and
Search for more papers by this authorR. Williams
Institute of Hepatology, University College London and University College London Hospitals,
Search for more papers by this authorG. Mieli-Vergani
Department of Child Health, King’s College Hospital, London, UK, and
Search for more papers by this authorD. Vergani
Institute of Hepatology, University College London and University College London Hospitals,
Search for more papers by this authorS. Fargion
Dipartimento di Medicina Interna, IRCCS Ospedale Maggiore, Milano, Italy
Search for more papers by this authorAbstract
The enzymes potentially involved in the pathogenesis of sporadic porphyria cutanea tarda (PCT) reside in liver cytosoles and microsomes. PCT is frequently associated with hepatitis C virus (HCV) infection, which is in turn associated with autoimmune manifestations. To investigate whether autoimmune reactions, possibly triggered by HCV, are involved in the pathogenesis of PCT, we measured by immunoblot autoantibodies to human cytosolic and microsomal liver fractions in 82 patients with PCT (77% with HCV infection), 105 with other liver disorders and 40 healthy subjects. Anti-liver cytosolic antibodies were more frequent in PCT patients (38/82, 46%) than in pathological 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 positive (36/63, 57%) than in HCV negative (2/19, 11%, P < 0·05) cases. Reactivity 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 anticytosolic antibodies as assessed by multivariate analysis. In contrast, frequency of antiliver microsomal antibodies was similar in PCT patients (24/82, 29%) and pathological controls (8–26%), being higher in the autoimmune hepatitis control group (23/23, 100%, P < 0·0001). In conclusion, anticytosolic antibodies, particularly to a 40-kDa polypeptide, are frequent in PCT and associated with HCV infection and severity of liver damage.
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