PMID- 30995924 OWN - NLM STAT- MEDLINE DCOM- 20191206 LR - 20200225 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 16 IP - 1 DP - 2019 Apr 17 TI - HLA and killer cell immunoglobulin-like receptor (KIRs) genotyping in patients with acute ischemic stroke. PG - 88 LID - 10.1186/s12974-019-1469-5 [doi] LID - 88 AB - INTRODUCTION: In humans, a major component of natural killer (NK) and T cell target recognition depends on the surveillance of human leukocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIRs). AIMS: To implement the knowledge about the immunological genetic background of acute ischemic stroke susceptibility in relation to the frequency of the KIR genes and HLA alleles. METHODS: Subjects with acute ischemic stroke and subjects without stroke were genotyped for the presence of KIR genes and of the three major KIR ligand groups, HLA-C1, HLA-C2, and HLA-Bw4, both HLA-B and HLA-A loci. RESULTS: Between November 2013 and February 2016, consecutive patients with acute ischemic stroke were recruited. As healthy controls, we enrolled subjects without acute ischemic stroke. Subjects with acute ischemic stroke in comparison with controls showed a higher frequency of 2DL3, 2DL5B, 2DS2, and 2DS4 KIR genes and a lower frequency of HLA-B-Bw4(I) alleles. Subjects without acute ischemic stroke showed a higher frequency of interaction between KIR 2DS2 and HLAC2. We also observed a higher frequency of 2DL3 and 2 DL4 KIR genes in subjects with atherosclerotic (LAAS) subtype. Multiple logistic regression analysis showed a protective effect towards stroke of HLA-B-Bw4(I) and interaction between KIR 2DL2 and HLAC1 and 2DS2-HLAC2 and a detrimental effect of 2DL2-HLA-C1_A interactions. CONCLUSION: Our findings of a higher frequency of activating KIR genes seem to be consistent with findings previously reported patients with coronary syndrome. This higher frequency of "proinflammatory" genes in subjects with ischemic stroke could also explain the immunoinflammatory activation of the acute phase of stroke. FAU - Tuttolomondo, Antonino AU - Tuttolomondo A AUID- ORCID: 0000-0001-6440-7318 AD - Internal Medicine and Stroke Care Ward, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, P.zza delle Cliniche n.2, 90127, Palermo, Italy. bruno.tuttolomondo@unipa.it. FAU - Di Raimondo, Domenico AU - Di Raimondo D AD - Internal Medicine and Stroke Care Ward, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, P.zza delle Cliniche n.2, 90127, Palermo, Italy. FAU - Pecoraro, Rosaria AU - Pecoraro R AD - Pronto Soccorso Unit, Giuseppe Giglio Hospital, Cefalu, Italy. AD - PhD Programme in Clinical Medicine and Behavioural Sciences, University of Palermo, Palermo, PA, 90133, Italy. FAU - Casuccio, Alessandra AU - Casuccio A AD - Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, P.zza delle Cliniche n.2, 90127, Palermo, Italy. FAU - Di Bona, Danilo AU - Di Bona D AD - School and Chair of Allergology, Dipartimento delle Emergenze e Trapianti d'Organo, University of Bari, Bari, Italy. FAU - Aiello, Anna AU - Aiello A AD - Dipartimento di Biopatologia e Biotecnologie Mediche, Universita' degli Studi di Palermo, Palermo, Italy. FAU - Accardi, Giulia AU - Accardi G AD - Dipartimento di Biopatologia e Biotecnologie Mediche, Universita' degli Studi di Palermo, Palermo, Italy. FAU - Arnao, Valentina AU - Arnao V AD - Dipartimento di BioMedicina Sperimentale e Neuroscienze Cliniche, Universita degli Studi di Palermo, Palermo, Italy. FAU - Clemente, Giuseppe AU - Clemente G AD - Internal Medicine and Stroke Care Ward, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, P.zza delle Cliniche n.2, 90127, Palermo, Italy. FAU - Corte, Vittoriano Della AU - Corte VD AD - PhD Programme in Molecular and Clinical Medicine, University of Palermo, Palermo, PA, 90133, Italy. FAU - Maida, Carlo AU - Maida C AD - Internal Medicine and Stroke Care Ward, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, P.zza delle Cliniche n.2, 90127, Palermo, Italy. FAU - Simonetta, Irene AU - Simonetta I AD - Internal Medicine and Stroke Care Ward, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, P.zza delle Cliniche n.2, 90127, Palermo, Italy. FAU - Caruso, Calogero AU - Caruso C AD - Dipartimento di Biopatologia e Biotecnologie Mediche, Universita' degli Studi di Palermo, Palermo, Italy. FAU - Squatrito, Rosario AU - Squatrito R AD - Pronto Soccorso Unit, Giuseppe Giglio Hospital, Cefalu, Italy. FAU - Pinto, Antonio AU - Pinto A AD - Internal Medicine and Stroke Care Ward, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, P.zza delle Cliniche n.2, 90127, Palermo, Italy. CN - KIRIIND (KIR Infectious and Inflammatory Diseases) Collaborative Group LA - eng PT - Journal Article DEP - 20190417 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Receptors, KIR) SB - IM MH - Aged MH - Cross-Sectional Studies MH - Female MH - Genetic Predisposition to Disease/genetics MH - Genotype MH - Histocompatibility Antigens Class I/*genetics MH - Humans MH - Male MH - Middle Aged MH - Receptors, KIR/*genetics MH - Stroke/*genetics/*immunology PMC - PMC6471781 OTO - NOTNLM OT - HLA OT - Killer immunoglobulin-like receptors (KIRs) OT - Stroke COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This protocol study was approved by the Ethics Committee of the Policlinico P. Giaccone Hospital and of Giuseppe Giglia Hospital, Cefalu (Palermo). All patients gave their written informed consent to participate in the study, as well as for sampling and banking of the biological material. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. FIR - Tuttolomondo, Antonino IR - Tuttolomondo A FIR - Di Raimondo, Domenico IR - Di Raimondo D FIR - Di Bona, Danilo IR - Di Bona D FIR - Caruso, Calogero IR - Caruso C FIR - Pinto, Antonio IR - Pinto A EDAT- 2019/04/19 06:00 MHDA- 2019/12/18 06:00 PMCR- 2019/04/17 CRDT- 2019/04/19 06:00 PHST- 2018/11/25 00:00 [received] PHST- 2019/03/27 00:00 [accepted] PHST- 2019/04/19 06:00 [entrez] PHST- 2019/04/19 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/04/17 00:00 [pmc-release] AID - 10.1186/s12974-019-1469-5 [pii] AID - 1469 [pii] AID - 10.1186/s12974-019-1469-5 [doi] PST - epublish SO - J Neuroinflammation. 2019 Apr 17;16(1):88. doi: 10.1186/s12974-019-1469-5.