Expression of Killer Immunoglobulin Receptor Genes Among HIV-Infected Individuals with Non-AIDS Comorbidities

Overview

Journal J Immunol Res

Publisher Wiley

Specialty Allergy & Immunology

Date 2022 Jan 24

PMID 35071606

Authors

Farouk F Abou Hassan

Mirna Bou Hamdan

Khalil El Asmar

Nada M Melhem

Affiliations

Soon will be listed here.

Abstract

Combined antiretroviral therapy (cART) increased the life expectancy of people living with HIV (PLHIV) and remarkably reduced the morbidity and mortality associated with HIV infection. However, non-AIDS associated comorbidities including diabetes, hypertension, hyperlipidemia, and cardiovascular diseases (CVD) are increasingly reported among PLHIV receiving cART. Killer cell immunoglobulin receptors (KIRs) expressed on the surface of natural killer (NK) cells have been previously implicated in controlling HIV disease progression. The aim of this study is to investigate the role of KIRs in developing non-AIDS associated comorbidities among PLHIV. Demographic and behavioral data were collected from voluntary participants using a standardized questionnaire. Whole blood samples were collected for KIR genotyping. Hypertension (29.5%) and hyperlipidemia (29.5%) followed by diabetes (23.7%) and CVD (9.7%) were mainly reported among our study participants with higher rate of comorbid conditions observed among participants > 40 years old. The observed KIR frequency (OF) was ≥90% for inhibitory and , activating and the pseudogene among study participants. We detected significant differences in the expression of and ( = 0.038) between diabetic and nondiabetic and in the expression of between hypertensive and normotensive HIV-infected individuals ( = 0.047). Moreover, and were associated with significantly reduced odds of having CVD (OR 0.08; 95% CI: 0.01-0.69; = 0.022). Our study suggests the potential role of KIR in predisposition to non-AIDS comorbidities among PLHIV and underscores the need for more studies to further elucidate the role of KIRs in this population.

References

Sherman K, Rockstroh J, Thomas D . Human immunodeficiency virus and liver disease: An update. Hepatology. 2015; 62(6):1871-82. PMC: 4681629. DOI: 10.1002/hep.28150. View

Mikulak J, Oriolo F, Zaghi E, Di Vito C, Mavilio D . Natural killer cells in HIV-1 infection and therapy. AIDS. 2017; 31(17):2317-2330. PMC: 5892189. DOI: 10.1097/QAD.0000000000001645. View

Campbell K, Purdy A . Structure/function of human killer cell immunoglobulin-like receptors: lessons from polymorphisms, evolution, crystal structures and mutations. Immunology. 2011; 132(3):315-25. PMC: 3044898. DOI: 10.1111/j.1365-2567.2010.03398.x. View

Castilho J, Escuder M, Veloso V, Gomes J, Jayathilake K, Ribeiro S . Trends and predictors of non-communicable disease multimorbidity among adults living with HIV and receiving antiretroviral therapy in Brazil. J Int AIDS Soc. 2019; 22(1):e25233. PMC: 6351749. DOI: 10.1002/jia2.25233. View

Yindom L, Mendy M, Bodimeade C, Chambion C, Aka P, Whittle H . KIR content genotypes associate with carriage of hepatitis B surface antigen, e antigen and HBV viral load in Gambians. PLoS One. 2017; 12(11):e0188307. PMC: 5693433. DOI: 10.1371/journal.pone.0188307. View

Podhorzer A, Dirchwolf M, Machicote A, Belen S, Montal S, Paz S . The Clinical Features of Patients with Chronic Hepatitis C Virus Infections Are Associated with Killer Cell Immunoglobulin-Like Receptor Genes and Their Expression on the Surface of Natural Killer Cells. Front Immunol. 2018; 8:1912. PMC: 5760500. DOI: 10.3389/fimmu.2017.01912. View

Tuttolomondo A, Di Raimondo D, Pecoraro R, Casuccio A, Di Bona D, Aiello A . HLA and killer cell immunoglobulin-like receptor (KIRs) genotyping in patients with acute ischemic stroke. J Neuroinflammation. 2019; 16(1):88. PMC: 6471781. DOI: 10.1186/s12974-019-1469-5. View

Zhi D, Sun C, Sedimbi S, Luo F, Shen S, Sanjeevi C . Killer cell immunoglobulin-like receptor along with HLA-C ligand genes are associated with type 1 diabetes in Chinese Han population. Diabetes Metab Res Rev. 2011; 27(8):872-7. DOI: 10.1002/dmrr.1264. View

de Rham C, Hadaya K, Bandelier C, Ferrari-Lacraz S, Villard J . Expression of killer cell immunoglobulin-like receptors (KIRs) by natural killer cells during acute CMV infection after kidney transplantation. Transpl Immunol. 2014; 31(3):157-64. DOI: 10.1016/j.trim.2014.08.002. View

10.

Hunt P . HIV and aging: emerging research issues. Curr Opin HIV AIDS. 2014; 9(4):302-8. PMC: 4138123. DOI: 10.1097/COH.0000000000000072. View

11.

Rasoolinejad M, Najafi E, Hadadi A, Najafi M, Kalantari S, Moradmand-Badie B . Prevalence and Associated Risk Factors of Hyperglycemia and Diabetes Mellitus Among HIV Positive Patients in Tehran, Iran. Infect Disord Drug Targets. 2018; 19(3):304-309. DOI: 10.2174/1871526518666180723152715. View

12.

Farahat F, Alghamdi Y, Farahat A, Alqurashi A, Alburayk A, Alabbasi A . The prevalence of comorbidities among adult people diagnosed with HIV infection in a tertiary care hospital in western Saudi Arabia. J Infect Public Health. 2020; 13(11):1699-1704. DOI: 10.1016/j.jiph.2020.08.009. View

13.

Maruthamuthu S, Rajalingam R, Pandian K, Madasamy S, Manoharan M, Pitchai L . Inhibitory natural killer cell receptor KIR3DL1 with its ligand Bw4 constraints HIV-1 disease among South Indians. AIDS. 2018; 32(18):2679-2688. DOI: 10.1097/QAD.0000000000002028. View

14.

Osman A, Eltayeb-Elsheikh N, Mubasher M, Al Harthi H, Alharbi S, Hamza M . Investigation of activating and inhibitory killer cell immunoglobulin-like receptors and their putative ligands in type 1 diabetes (T1D). Hum Immunol. 2015; 77(1):110-114. DOI: 10.1016/j.humimm.2015.10.019. View

15.

Hasse B, Ledergerber B, Furrer H, Battegay M, Hirschel B, Cavassini M . Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study. Clin Infect Dis. 2011; 53(11):1130-9. DOI: 10.1093/cid/cir626. View

16.

Vance D, Mugavero M, Willig J, Raper J, Saag M . Aging with HIV: a cross-sectional study of comorbidity prevalence and clinical characteristics across decades of life. J Assoc Nurses AIDS Care. 2010; 22(1):17-25. DOI: 10.1016/j.jana.2010.04.002. View

17.

Smit M, Brinkman K, Geerlings S, Smit C, Thyagarajan K, van Sighem A . Future challenges for clinical care of an ageing population infected with HIV: a modelling study. Lancet Infect Dis. 2015; 15(7):810-8. PMC: 4528076. DOI: 10.1016/S1473-3099(15)00056-0. View

18.

Jobim M, Salim P, Portela P, Wilson T, Fraportti J, Baronio D . Killer cell immunoglobulin-like receptor gene diversity in a Caucasian population of southern Brazil. Int J Immunogenet. 2010; 37(2):83-9. DOI: 10.1111/j.1744-313X.2009.00894.x. View

19.

Bashirova A, Thomas R, Carrington M . HLA/KIR restraint of HIV: surviving the fittest. Annu Rev Immunol. 2011; 29:295-317. PMC: 3725604. DOI: 10.1146/annurev-immunol-031210-101332. View

20.

Wang A, Jiang B, Qian X, Zhang Q, Peng H, Zhang Y . Association between killer cell immunoglobulin-like receptor 2DS5 gene with essential hypertension in the Chinese Han patients. Int J Immunogenet. 2017; 44(6):343-349. DOI: 10.1111/iji.12342. View