The effects of killer cell immunoglobulin-like receptor (KIR) genes on susceptibility to severe COVID-19 in the Iranian population.
COVID-19
Killer cell immunoglobulin-like receptors (KIRs)
NK cell
Journal
BMC immunology
ISSN: 1471-2172
Titre abrégé: BMC Immunol
Pays: England
ID NLM: 100966980
Informations de publication
Date de publication:
28 Jun 2024
28 Jun 2024
Historique:
received:
19
10
2023
accepted:
13
06
2024
medline:
29
6
2024
pubmed:
29
6
2024
entrez:
29
6
2024
Statut:
epublish
Résumé
Variations in the innate and adaptive immune response systems are linked to variations in the severity of COVID-19. Natural killer cell (NK) function is regulated by sophisticated receptor system including Killer-cell immunoglobulin-like receptor (KIR) family. We aimed to investigate the impact of possessing certain KIR genes and genotypes on COVID19 severity in Iranians. KIR genotyping was performed on 394 age/sex matched Iranians with no underlying conditions who developed mild and severe COVID- 19. The presence and/or absence of 11 KIR genes were determined using the PCR with sequence specific primers (PCR-SSP). Patients with mild symptoms had higher frequency ofKIR2DS1 (p = 0.004) and KIR2DS2 (p = 0.017) genes compared to those with severe disease. While KIR3DL3 and deleted variant of KIR2DS4 occurred more frequently in patients who developed a severe form of the disease. In this study, a significant increase of and B haplotype was observed in the Mild group compared to the Severe group (respectively, p = 0.002 and p = 0.02). Also, the prevalence of haplotype A was significantly higher in the Severe group than in the Mild group (p = 0.02). These results suggest that the KIR2DS1, KIR2DS, and B haplotype maybe have a protective effect against COVID-19 severity. The results also suggest the inhibitory gene KIR2DL3 and haplotype A are risk factors for the severity of COVID-19.
Sections du résumé
BACKGROUND
BACKGROUND
Variations in the innate and adaptive immune response systems are linked to variations in the severity of COVID-19. Natural killer cell (NK) function is regulated by sophisticated receptor system including Killer-cell immunoglobulin-like receptor (KIR) family. We aimed to investigate the impact of possessing certain KIR genes and genotypes on COVID19 severity in Iranians. KIR genotyping was performed on 394 age/sex matched Iranians with no underlying conditions who developed mild and severe COVID- 19. The presence and/or absence of 11 KIR genes were determined using the PCR with sequence specific primers (PCR-SSP).
RESULTS
RESULTS
Patients with mild symptoms had higher frequency ofKIR2DS1 (p = 0.004) and KIR2DS2 (p = 0.017) genes compared to those with severe disease. While KIR3DL3 and deleted variant of KIR2DS4 occurred more frequently in patients who developed a severe form of the disease. In this study, a significant increase of and B haplotype was observed in the Mild group compared to the Severe group (respectively, p = 0.002 and p = 0.02). Also, the prevalence of haplotype A was significantly higher in the Severe group than in the Mild group (p = 0.02).
CONCLUSIONS
CONCLUSIONS
These results suggest that the KIR2DS1, KIR2DS, and B haplotype maybe have a protective effect against COVID-19 severity. The results also suggest the inhibitory gene KIR2DL3 and haplotype A are risk factors for the severity of COVID-19.
Identifiants
pubmed: 38943065
doi: 10.1186/s12865-024-00631-1
pii: 10.1186/s12865-024-00631-1
doi:
Substances chimiques
Receptors, KIR
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
38Informations de copyright
© 2024. The Author(s).
Références
Rahman S, et al. Epidemiology, pathogenesis, clinical presentations, diagnosis and treatment of COVID-19: a review of current evidence. Expert Rev Clin Pharmacol. 2021;14(5):601–21.
doi: 10.1080/17512433.2021.1902303
pubmed: 33705239
Yang L, et al. COVID-19: immunopathogenesis and immunotherapeutics. Signal Transduct Target Therapy. 2020;5(1):1–8.
https://covid19.who.int/table.
Melis M, Littera R. Undetected infectives in the Covid-19 pandemic. Int J Infect Dis. 2021;104:262–8.
doi: 10.1016/j.ijid.2021.01.010
pubmed: 33434673
pmcid: 7837159
Backer JA, Klinkenberg D, Wallinga J. Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020. Eurosurveillance. 2020;25(5):2000062.
doi: 10.2807/1560-7917.ES.2020.25.5.2000062
pubmed: 32046819
pmcid: 7014672
Littera R, et al. Natural killer-cell immunoglobulin-like receptors trigger differences in immune response to SARS-CoV-2 infection. PLoS ONE. 2021;16(8):e0255608.
doi: 10.1371/journal.pone.0255608
pubmed: 34352002
pmcid: 8341547
Rippinger C, et al. Evaluation of undetected cases during the COVID-19 epidemic in Austria. BMC Infect Dis. 2021;21(1):1–11.
doi: 10.1186/s12879-020-05737-6
Lee MJ, Blish CA. Defining the role of natural killer cells in COVID-19. Nat Immunol. 2023;24(10):1628–38.
doi: 10.1038/s41590-023-01560-8
pubmed: 37460639
pmcid: 10538371
Mele D, et al. Long-term dynamics of natural killer cells in response to SARS‐CoV‐2 vaccination: persistently enhanced activity postvaccination. J Med Virol. 2024;96(4):e29585.
doi: 10.1002/jmv.29585
pubmed: 38566585
Rajalingam R. Human diversity of killer cell immunoglobulin-like receptors and disease. Korean J Hematol. 2011;46(4):216.
doi: 10.5045/kjh.2011.46.4.216
pubmed: 22259627
pmcid: 3259513
Pende D, et al. Killer Ig-like receptors (KIRs): their role in NK cell modulation and developments leading to their clinical exploitation. Front Immunol. 2019;10:461739.
doi: 10.3389/fimmu.2019.01179
Rajalingam R. Overview of the killer cell immunoglobulin-like receptor system. Immunogenetics: Methods and Applications in Clinical Practice, 2012: pp. 391–414.
Barani S, Hosseini SV, Ghaderi A. Activating and inhibitory killer cell immunoglobulin like receptors (KIR) genes are involved in an increased susceptibility to colorectal adenocarcinoma and protection against invasion and metastasis. Immunobiology. 2019;224(5):681–6.
doi: 10.1016/j.imbio.2019.06.002
pubmed: 31248612
Parham P, et al. Human-specific evolution of killer cell immunoglobulin-like receptor recognition of major histocompatibility complex class I molecules. Philosophical Trans Royal Soc B: Biol Sci. 2012;367(1590):800–11.
doi: 10.1098/rstb.2011.0266
Barani S, et al. KIR2DS1, 2DS5, 3DS1 and KIR2DL5 are associated with the risk of head and neck squamous cell carcinoma in iranians. Hum Immunol. 2018;79(4):218–23.
doi: 10.1016/j.humimm.2018.01.012
pubmed: 29408295
Martin AM, et al. The genomic organization and evolution of the natural killer immunoglobulin-like receptor (KIR) gene cluster. Immunogenetics. 2000;51:268–80.
doi: 10.1007/s002510050620
pubmed: 10803839
Vilches C, Parham P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol. 2002;20(1):217–51.
doi: 10.1146/annurev.immunol.20.092501.134942
pubmed: 11861603
Maruthamuthu S, et al. Individualized constellation of killer cell immunoglobulin-like receptors and cognate HLA class I ligands that controls natural killer cell antiviral immunity predisposes COVID-19. Front Genet. 2022;13:845474.
doi: 10.3389/fgene.2022.845474
pubmed: 35273641
pmcid: 8902362
Bernal E, et al. Activating killer-cell immunoglobulin-like receptors are associated with the severity of coronavirus disease 2019. J Infect Dis. 2021;224(2):229–40.
doi: 10.1093/infdis/jiab228
pubmed: 33928374
Hajeer A, et al. Association of KIR gene polymorphisms with COVID-19 disease. Clin Immunol. 2022;234:108911.
doi: 10.1016/j.clim.2021.108911
pubmed: 34929414
Aranda-Romo S, et al. Killer-cell immunoglobulin-like receptors (KIR) in severe A (H1N1) 2009 influenza infections. Immunogenetics. 2012;64(9):653–62.
doi: 10.1007/s00251-012-0623-3
pubmed: 22652695
MWer S, Dykes D, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids res. 1988;16(3):1215.
doi: 10.1093/nar/16.3.1215
Ashouri E, et al. KIR gene content diversity in four Iranian populations. Immunogenetics. 2009;61:483–92.
doi: 10.1007/s00251-009-0378-7
pubmed: 19521696
pmcid: 2706385
Vilches C, et al. Facilitation of KIR genotyping by a PCR-SSP method that amplifies short DNA fragments. Tissue Antigens. 2007;70(5):415–22.
doi: 10.1111/j.1399-0039.2007.00923.x
pubmed: 17854430
Barani S, Taghipour M, Ghaderi A. Positive association of bx genotype, KIR2L5, KIR2DS5 and full-length KIR2DS4 with the risk of meningioma. Immunobiology. 2020;225(2):151900.
doi: 10.1016/j.imbio.2019.151900
pubmed: 31899050
Barani S, Khademi B, Ghaderi A. KIR2DS4, KIR2DL2, and KIR2DS4del are linked with basaloid tumors, lymph node metastasis, advanced stage and metastatic risk in head and neck squamous cell carcinoma. Exp Mol Pathol. 2020;112:104345.
doi: 10.1016/j.yexmp.2019.104345
pubmed: 31751561
Samadizadeh S, et al. COVID-19: why does disease severity vary among individuals? Respir Med. 2021;180:106356.
doi: 10.1016/j.rmed.2021.106356
pubmed: 33713961
pmcid: 7934673
Hasabo EA, et al. Clinical manifestations, complications, and outcomes of patients with COVID-19 in Sudan: a multicenter observational study. Trop Med Health. 2021;49(1):1–13.
doi: 10.1186/s41182-021-00382-4
Zucchini N, et al. Natural killer cells in immunodefense against infective agents. Expert Rev anti-infective Therapy. 2008;6(6):867–85.
doi: 10.1586/14787210.6.6.867
pubmed: 19053900
Abel AM, et al. Natural killer cells: development, maturation, and clinical utilization. Front Immunol. 2018;9:1869.
doi: 10.3389/fimmu.2018.01869
pubmed: 30150991
pmcid: 6099181
Lesan V, et al. Killer immunoglobulin-like receptor 2DS5 is associated with recovery from coronavirus disease 2019. Intensive Care Med Experimental. 2021;9:1–10.
doi: 10.1186/s40635-021-00409-4
Deborska-Materkowska D, et al. Killer immunoglobulin-like receptor 2DS2 (KIR2DS2), KIR2DL2-HLA-C1, and KIR2DL3 as genetic markers for stratifying the risk of cytomegalovirus infection in kidney transplant recipients. Int J Mol Sci. 2019;20(3):546.
doi: 10.3390/ijms20030546
pubmed: 30696053
pmcid: 6387393
Bonagura VR, et al. Activating killer cell immunoglobulin-like receptors 3DS1 and 2DS1 protect against developing the severe form of recurrent respiratory papillomatosis. Hum Immunol. 2010;71(2):212–9.
doi: 10.1016/j.humimm.2009.10.009
pubmed: 19861144
Aranda-Romo S, et al. Killer-cell immunoglobulin-like receptors (KIR) in severe A (H1N1) 2009 influenza infections. Immunogenetics. 2012;64:653–62.
doi: 10.1007/s00251-012-0623-3
pubmed: 22652695
de Meira Leite M, et al. Predictive immunogenetic markers in COVID-19. Hum Immunol. 2021;82(4):247–54.
doi: 10.1016/j.humimm.2021.01.008
Hu S et al. The KIR2DL2/HLA-C1C1 gene pairing is Associated with an increased risk of SARS-CoV-2 infection. Front Immunol, 2022. 13.
Maruthamuthu S et al. Individualized constellation of killer cell immunoglobulin-like receptors and cognate HLA class I ligands that controls natural killer cell antiviral immunity predisposes COVID-19. Front Genet, 2022. 13.
Zaia JA, et al. The effect of single and combined activating killer immunoglobulin-like receptor genotypes on cytomegalovirus infection and immunity after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2009;15(3):315–25.
doi: 10.1016/j.bbmt.2008.11.030
pubmed: 19203722
pmcid: 2770248