CD4 recovery is associated with genetic variation in IFN gamma and IL19 genes
Por:
García M, Jiménez-Sousa MA, Blanco J, Restrepo C, Pacheco YM, Brochado-Kith Ó, López-Bernaldo JC, Gutiérrez F, Portilla J, Estrada V, Górgolas M, Cabello A, Resino S, Benito JM and Rallón N
Publicada:
1 oct 2019
Resumen:
Not all HIV-infected patients receiving cART are able to recover optimal CD4-T cell levels despite achieving undetectable viremia. We evaluated the potential association between polymorphisms (SNPs) in cytokines involved in immune response (IL15, IFN gamma and IL19) and the failure to achieve optimal CD4 T-cells restoration after cART. For this, we carried out a retrospective study in 412 HIV-infected patients starting cART with CD4 < 200 cells/mu L. These patients were classified as immunological non-responders (INR) if having a CD4 increase (Delta CD4) below 200 cells/mu L after two years on successful cART. IL15, IFN gamma and IL19 polymorphisms were genotyped using Sequenom's MassARRAY platform. We found 134 INR patients with a median [IQR] Delta CD4 = 133[73-174] cells/mu L. In the multivariate analysis adjusted for age, sex, infection route, ethnic origin, hepatitis co-infection and HIV infection length, the AA genotype of the SNP rs2430561 in IFN gamma (OR:2.01[1.13-3.56], p=0.017) and the TT genotype of polymorphism rs2243191 in IL19 (OR:2.58 [1.17-5.68], p=0.019) showed significant association with the INR status. Our results show that polymorphisms in IFN gamma and IL19 genes significantly impacts in the probability of not achieving an optimal immune recovery in HIV-patients starting cART with CD4 T-cells < 200 cells/mu L. Thus, these SNPs could represent potential predictive markers of the immunodiscordant response.
Filiaciones:
García M:
HIV and Viral Hepatitis Research Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Hospital Universitario Rey Juan Carlos, Móstoles, Spain
Jiménez-Sousa MA:
Instituto de Salud Carlos III, Madrid, Spain
Blanco J:
IrsiCaixa AIDS Research Institute, Badalona, Spain
Restrepo C:
HIV and Viral Hepatitis Research Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Hospital Universitario Rey Juan Carlos, Móstoles, Spain
Pacheco YM:
Laboratory of Immunology, Instituto de Biomedicina de Sevilla (IBiS)/UGC Clinical Laboratories, Hospital Universitario Virgen del Rocío, Sevilla, Spain
Brochado-Kith Ó:
Instituto de Salud Carlos III, Madrid, Spain
López-Bernaldo JC:
Hospital General Universitario Gregorio Marañón, Madrid, Spain
:
Hospital General Universitario de Elche & Universidad Miguel Hernández, Alicante, Spain
Portilla J:
Hospital General Universitario de Alicante, Alicante, Spain
Estrada V:
Hospital Universitario Clínico San Carlos, Madrid, Spain
Górgolas M:
Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
Cabello A:
Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
Resino S:
Instituto de Salud Carlos III, Madrid, Spain
Benito JM:
HIV and Viral Hepatitis Research Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Hospital Universitario Rey Juan Carlos, Móstoles, Spain
Rallón N:
HIV and Viral Hepatitis Research Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Hospital Universitario Rey Juan Carlos, Móstoles, Spain
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