Practical laboratory medicine · 2023
Liver kidney microsome antibodies. Analysis of a laboratory series.
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Sanchez Sandra, Fang Diana, Xiao Shaoming, Rezavi Lu Ann, Howard Brittney M, Caturegli Patrizio, Cihakova Daniela
Аннотация
OBJECTIVES: The objectives were to characterize the liver kidney microsome (LKM) antibody profile of a 14-month-old girl with autoimmune hepatitis and analyze the laboratory prevalence of LKM positivity.
DESIGN AND METHODS: This is retrospective analysis of the LKM antibody immunofluorescence tests performed by the Immunology Laboratory of Johns Hopkins Hospital from September 8, 2020 to July 31, 2022. LKM positive sera were also tested by an ELISA for LKM1 antibodies, which recognize the cytochrome P450 2D6 antigen. In silico analysis of 2D6 mRNA expression across anatomical sites was performed using Bgee and GTEx Portal databases.
RESULTS: Of the total of 1598 patients (893 F, 705 M, ages 0.8-94 years) tested for LKM antibodies, 3 were positive, yielding a 0.2% period prevalence. The clinical diagnosis was autoimmune hepatitis in the index case, acute viral hepatitis in a 3-yo male, and hepatocellular carcinoma in a 54-yo male. LKM antibodies yielded the classical homogenous staining pattern in the liver cytosol and proximal kidney tubular cells. The first two patients were also positive for LKM1 antibodies, whereas the third was negative. 2D6 mRNA was expressed highly in the liver, moderately in the duodenum, and minimally in other tissues.
CONCLUSIONS: Overall, LKM antibodies are rare. They contribute to establish a diagnosis of autoimmune hepatitis, although they are also found in other liver diseases. The cytochrome P450 2D6 is one of the antigens recognized by LKM antibodies, but other antigens are likely targeted considering that 2D6 is minimally expressed in the kidney and yet LKM antibodies bind to kidney tubuli.
DESIGN AND METHODS: This is retrospective analysis of the LKM antibody immunofluorescence tests performed by the Immunology Laboratory of Johns Hopkins Hospital from September 8, 2020 to July 31, 2022. LKM positive sera were also tested by an ELISA for LKM1 antibodies, which recognize the cytochrome P450 2D6 antigen. In silico analysis of 2D6 mRNA expression across anatomical sites was performed using Bgee and GTEx Portal databases.
RESULTS: Of the total of 1598 patients (893 F, 705 M, ages 0.8-94 years) tested for LKM antibodies, 3 were positive, yielding a 0.2% period prevalence. The clinical diagnosis was autoimmune hepatitis in the index case, acute viral hepatitis in a 3-yo male, and hepatocellular carcinoma in a 54-yo male. LKM antibodies yielded the classical homogenous staining pattern in the liver cytosol and proximal kidney tubular cells. The first two patients were also positive for LKM1 antibodies, whereas the third was negative. 2D6 mRNA was expressed highly in the liver, moderately in the duodenum, and minimally in other tissues.
CONCLUSIONS: Overall, LKM antibodies are rare. They contribute to establish a diagnosis of autoimmune hepatitis, although they are also found in other liver diseases. The cytochrome P450 2D6 is one of the antigens recognized by LKM antibodies, but other antigens are likely targeted considering that 2D6 is minimally expressed in the kidney and yet LKM antibodies bind to kidney tubuli.