Detection of Liver Kidney Microsomal Type 1 Antibody Using Molecularly Based Immunoassays

Overview

Journal J Clin Pathol

Specialty Pathology

Date 2002 Dec 4

PMID 12461054

Citations 4

Authors

N Kerkar

Y Ma

E T Davies

P Cheeseman

G Mieli-Vergani

D Vergani

Affiliations

Soon will be listed here.

Abstract

Aims: To assess the diagnostic value of two commercial molecularly based immunoassays detecting liver kidney microsomal type 1 antibody (LKM1).

Methods: The performance of Varelisa and LKM1 enzyme linked immunosorbent assay (ELISA) was compared with immunofluorescence, and two validated research techniques-an in house ELISA and a radioligand assay measuring antibodies to P4502D6. Thirty serum samples from three patients with autoimmune hepatitis type 2 covering immunofluorescence titres of 1/10 to 1/10 240 and 55 LKM1 negative controls were tested.

Results: All 30 sera that were LKM1 positive by immunofluorescence were positive by the in house ELISA, the radioligand assay, and LKM1-ELISA, and 29 were also positive by Varelisa. None of the 55 sera negative for LKM1 by immunofluorescence was positive by the in house ELISA and radioligand assay, but one was positive by Varelisa and 14 were positive using the LKM1-ELISA. Agreement between immunofluorescence, the in house ELISA, the radioligand assay, and Varelisa was high (kappa > 0.8), and agreement between immunofluorescence and LKM1-ELISA was moderate (kappa = 0.63).

Conclusion: The assay kit marketed as Varelisa allows accurate detection of LKM1.

Citing Articles

Evaluation of immunoserological detection of anti-liver kidney microsomal, anti-soluble liver antigen and anti-mitochondrial antibodies.

Campos-Murguia A, Henjes N, Loges S, Wedemeyer H, Jaeckel E, Taubert R Sci Rep. 2023; 13(1):10038.

PMID: 37340049 PMC: 10282044. DOI: 10.1038/s41598-023-37095-z.

Autoantibodies in Autoimmune Liver Disease-Clinical and Diagnostic Relevance.

Sebode M, Weiler-Normann C, Liwinski T, Schramm C Front Immunol. 2018; 9:609.

PMID: 29636752 PMC: 5880919. DOI: 10.3389/fimmu.2018.00609.

Antihistone Autoantibodies in Dobermans With Hepatitis.

Dyggve H, Meri S, Spillmann T, Jarva H, Speeti M J Vet Intern Med. 2017; 31(6):1717-1723.

PMID: 28963850 PMC: 5697184. DOI: 10.1111/jvim.14838.

Autoimmune liver serology: current diagnostic and clinical challenges.

Bogdanos D, Invernizzi P, Mackay I, Vergani D World J Gastroenterol. 2008; 14(21):3374-87.

PMID: 18528935 PMC: 2716592. DOI: 10.3748/wjg.14.3374.

References

Rizzetto M, Swana G, Doniach D . Microsomal antibodies in active chronic hepatitis and other disorders. Clin Exp Immunol. 1973; 15(3):331-44. PMC: 1553909. View

Alvarez F, Berg P, Bianchi F, Bianchi L, Burroughs A, Cancado E . International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999; 31(5):929-38. DOI: 10.1016/s0168-8278(99)80297-9. View

Landis J, Koch G . The measurement of observer agreement for categorical data. Biometrics. 1977; 33(1):159-74. View

Kenny R, Czaja A, Ludwig J, Dickson E . Frequency and significance of antimitochondrial antibodies in severe chronic active hepatitis. Dig Dis Sci. 1986; 31(7):705-11. DOI: 10.1007/BF01296447. View

HOMBERG J, Abuaf N, Bernard O, Islam S, Alvarez F, Khalil S . Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: a second type of "autoimmune" hepatitis. Hepatology. 1987; 7(6):1333-9. DOI: 10.1002/hep.1840070626. View

Zanger U, Hauri H, Loeper J, HOMBERG J, Meyer U . Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II. Proc Natl Acad Sci U S A. 1988; 85(21):8256-60. PMC: 282408. DOI: 10.1073/pnas.85.21.8256. View

Martini E, Abuaf N, Cavalli F, Durand V, Johanet C, HOMBERG J . Antibody to liver cytosol (anti-LC1) in patients with autoimmune chronic active hepatitis type 2. Hepatology. 1988; 8(6):1662-6. DOI: 10.1002/hep.1840080632. View

Manns M, Johnson E, Griffin K, Tan E, Sullivan K . Major antigen of liver kidney microsomal autoantibodies in idiopathic autoimmune hepatitis is cytochrome P450db1. J Clin Invest. 1989; 83(3):1066-72. PMC: 303785. DOI: 10.1172/JCI113949. View

Gueguen M, Yamamoto A, Bernard O, Alvarez F . Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1. Biochem Biophys Res Commun. 1989; 159(2):542-7. DOI: 10.1016/0006-291x(89)90027-2. View

10.

Czaja A, Manns M, Homburger H . Frequency and significance of antibodies to liver/kidney microsome type 1 in adults with chronic active hepatitis. Gastroenterology. 1992; 103(4):1290-5. DOI: 10.1016/0016-5085(92)91518-9. View

11.

Seelig R, Renz M, Bunger G, Schroter H, Seelig H . Anti-LKM-1 antibodies determined by use of recombinant P450 2D6 in ELISA and western blot and their association with anti-HCV and HCV-RNA. Clin Exp Immunol. 1993; 92(3):373-80. PMC: 1554777. DOI: 10.1111/j.1365-2249.1993.tb03408.x. View

12.

Gregorio G, Portmann B, Reid F, Donaldson P, Doherty D, McCartney M . Autoimmune hepatitis in childhood: a 20-year experience. Hepatology. 1997; 25(3):541-7. DOI: 10.1002/hep.510250308. View

13.

Yamamoto A, Johanet C, Duclos-Vallee J, Bustarret F, Alvarez F, HOMBERG J . A new approach to cytochrome CYP2D6 antibody detection in autoimmune hepatitis type-2 (AIH-2) and chronic hepatitis C virus (HCV) infection: a sensitive and quantitative radioligand assay. Clin Exp Immunol. 1997; 108(3):396-400. PMC: 1904695. DOI: 10.1046/j.1365-2249.1997.4071302.x. View

14.

Ma Y, Gregorio G, Gaken J, Muratori L, Bianchi F, Mieli-Vergani G . Establishment of a novel radioligand assay using eukaryotically expressed cytochrome P4502D6 for the measurement of liver kidney microsomal type 1 antibody in patients with autoimmune hepatitis and hepatitis C virus infection. J Hepatol. 1997; 26(6):1396-402. DOI: 10.1016/s0168-8278(97)80477-1. View

15.

Kerkar N, Ma Y, Hussain M, Muratori L, Targett C, Williams R . A novel assay for detecting antibodies to cytochrome P4502D6, the molecular target of liver kidney microsomal antibody type 1. J Immunol Methods. 1999; 223(2):227-35. DOI: 10.1016/s0022-1759(98)00213-0. View

16.

Smith M, Williams R, Walker G, Rizzetto M, Doniach D . Hepatic disorders associated with liver-kidney microsomal antibodies. Br Med J. 1974; 2(5910):80-4. PMC: 1610709. DOI: 10.1136/bmj.2.5910.80. View