Oncotarget

Research Papers:

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

Antonino Tuttolomondo _, Claudia Colomba, Danilo Di Bona, Alessandra Casuccio, Domenico Di Raimondo, Giuseppe Clemente, Valentina Arnao, Rosaria Pecoraro, Paolo Ragonese, Anna Aiello, Giulia Accardi, Rosario Maugeri, Carlo Maida, Irene Simonetta, Vittoriano Della Corte, Domenico Gerardo Iacopino, Calogero Caruso, Antonio Cascio, Antonio Pinto and on behalf of KIRIIND (KIR Infectious and Inflammatory Diseases) Collaborative Group

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Oncotarget. 2018; 9:17523-17532. https://doi.org/10.18632/oncotarget.24778

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Abstract

Antonino Tuttolomondo1, Claudia Colomba2, Danilo Di Bona6, Alessandra Casuccio4, Domenico Di Raimondo1, Giuseppe Clemente1, Valentina Arnao5, Rosaria Pecoraro1, Paolo Ragonese5, Anna Aiello3, Giulia Accardi3, Rosario Maugeri5, Carlo Maida1, Irene Simonetta1, Vittoriano Della Corte1, Domenico Gerardo Iacopino5, Calogero Caruso3, Antonio Cascio2 and Antonio Pinto1 on behalf of KIRIIND (KIR Infectious and Inflammatory Diseases) Collaborative Group

1U.O.C di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), Università degli Studi di Palermo, Palermo, Italy

2U.O.C di Malattie Infettive, Dipartimento di Scienze per la Promozione della Salute e Materno Infantile G. D'Alessandro, Università degli Studi di Palermo, Palermo, Italy

3Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, Palermo, Italy

4Dipartimento di Scienze per la Promozione della Salute e Materno Infantile “G. D'Alessandro”, Università degli Studi di Palermo, Palermo, Italy

5Dipartimento di BioMedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Palermo, Italy

6School of Allergology, Dipartimento delle Emergenze e Trapianti d'Organo, University of Bari, Bari, Italy

Correspondence to:

Antonino Tuttolomondo, email: [email protected]

Keywords: KIRs; HLA; encephalitis

Received: December 11, 2017     Accepted: February 25, 2018     Published: April 03, 2018

ABSTRACT

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.

Results: Subjects 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.

Discussion: Our 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 Methods: 30 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).


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