HLA and killer cell immunoglobulin-like receptor (KIRs) genotyping in patients with acute viral encephalitis.

Antonino Tuttolomondo,Domenico Gerardo Iacopino,Danilo Di Bona,Rosaria Pecoraro,Vittoriano Della Corte,Antonio Cascio,Valentina Arnao,Carlo Maida,Giuseppe Clemente,Antonio Pinto,Giulia Accardi,Anna Aiello,Irene Simonetta,Domenico Di Raimondo,Rosario Maugeri,Calogero Caruso,Paolo Ragonese,Alessandra Casuccio,Claudia Colomba

doi:10.18632/oncotarget.24778

Antonino Tuttolomondo, Domenico Gerardo Iacopino + Show 17 more

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https://doi.org/10.18632/oncotarget.24778

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Abstract

IntroductionThe HLA genes, as well as the innate immune KIR genes, are considered relevant determinants of viral outcomes but no study, to our knowledge, has evaluated their role in the clinical setting of acute viral encephalitis.ResultsSubjects with acute viral encephalitis in comparison to subjects without acute viral encephalitis showed a significantly higher frequency of 2DL1 KIR gene and AA KIR haplotypes and of HLA-C2 and HLA-A-Bw4 alleles. Subjects without acute viral encephalitis showed a higher frequency of interaction between KIR2DL2 and HLAC1. Multiple logistic regression analysis showed the detrimental effect of HLA-A haplotype and HLA-C1, HLA-A-BW4 HLA-B-BW4T alleles, whereas multiple logistic regression showed a protective effect of AB+BB KIR haplotype and a detrimental effect of interaction between KIR3DL1 and HLA-A-Bw4.DiscussionOur findings of a lower frequency of activating receptors in patients with acute encephalitis compared to controls could result in a less efficient response of NK cells. This finding could represent a possible pathogenetic explanation of susceptibility to acute symptomatic encephalitis in patients with viral infection from potentially responsible viruses such as Herpes virus.Materials and Methods30 Consecutive patients with symptomatic acute viral encephalitis and as controls, 36 consecutive subjects without acute encephalitis were analyzed. The following KIR genes were analyzed, KIR2DL1, 2DL2, 2DL3, 2DL5, 3DL1, 3DL2, 3DL3, 2DL4, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DS1, 2 pseudogenes (2DP1 and 3DP1) and the common variants of KIR2DL5 (KIR2DL5A, KIR2DL5B).

Highlights

The human leukocyte antigen (HLA) genes, as well as the innate immune killer immunoglobulin-like receptors (KIRs) genes, are considered relevant determinants of viral outcomes but no study, to our knowledge, has evaluated their role in the clinical setting of acute viral encephalitis
Subjects without acute viral encephalitis showed a higher frequency of interaction between KIR2DL2 and HLAC1
Multiple logistic regression analysis showed the detrimental effect of HLA-A haplotype and HLA-C1, HLA-A-BW4 HLA-B-BW4T alleles, whereas multiple logistic regression showed a protective effect of AB+BB KIR haplotype and a detrimental effect of interaction between KIR3DL1 and HLA-A-Bw4

Summary

Introduction

The HLA genes, as well as the innate immune KIR genes, are considered relevant determinants of viral outcomes but no study, to our knowledge, has evaluated their role in the clinical setting of acute viral encephalitis. Acute encephalitis is a severe form of neurological disease caused by inflammation of the brain parenchyma. It is commonly characterized by the acute onset of fever, altered mental status, new onset of focal neurological symptoms, and generalized or focal seizures. It can be produced by various etiologies, but viral infection and autoimmune disorders are the most common [1, 2]. Natural killer (NK) cell activation or inhibition pathways mediated by HLA expression could have a potential detrimental or protective role in viral encephalitis onset in immunocompetent hosts [4,5,6,7,8,9,10]. NK cell target recognition is strictly linked to the role of human leukocyte antigen (HLA) class I molecules and of killer immunoglobulin-like receptors (KIRs), activating or inhibitory receptors on the surface of NK cells and T-cells [11]

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