Increased gene frequency of KIR2DS4 in autoinmune hepatitis

N. PALADINO; A.C. FLORES; A. PODHORZER; T. SHROEDER; H.A. FAINBOIM; L. FAINBOIM

Congreso; 13th Meeting of the Society for Natural Immunity; 2012

INTRODUCTION. A previous study from our lab revealed a difference in thegenetic predisposition to autoimmune hepatitis (AH) between children (PAH) andadults (AAH). The haplotype HLA-DRB1*1301-DQB1*0603 is associated withPAH. HLA-DRB1*0405 predisposes to AAH, with an additional effect of HLA-A11in increasing the likelihood of patients to develop extra hepatic autoimmunemanifestations. The present study is orientated to detect genetic differences inPAH and AAH within the KIR locus.METHODS. The study included 420 healthy controls, 73 pediatric (PAH) and 51adult (AAH) type I autoimmune hepatitis. Genomic DNA was used to identify thepresence or absence of each 16 KIR genes, by two PCR amplifications: PCR-1for domains D1 and D2 combined and the PCR-2 for thetransmembrane/cytoplasmic region. The KIR2DS4 gene was amplified by PCRwith primers previously described to analyze the full-length and the deletedversion of the KIR2DS4 gene. HLA-Cw genotyping was performed within exons 2and 3 of the HLA-C gene. SSOP typing used probes specific for the HLA-Calleles that belong to the C1 group (Asn 80) and to the C2 group (Lys 80)RESULTS. The frequencies of 2DL1, 2DL2, 2DL3, 2DL5 3DL1, 2DS1, 2DS2,2DS3, 2DS4, 2DS5, 3DS1 and 2DP1 were similar in controls and in AAH andPAH. In our Argentinean Caucasoid healthy population, KIR2DS4-allelescontaining the 22 bp deletion in exon 5 account for 81%. The frequency of thefull-length gene in our population is 40%, frequencies similarly reported in otherCaucasoid populations (Middleton et al 2007). In contrast, the full-length2DS4*001 allotype was present in 68% of PAH, 53% of AAH and in 38% ofcontrols. The differences between PAH and controls was highly significant(p