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OMICS. 2019 Feb;23(2):111-118. doi: 10.1089/omi.2018.0147. Epub 2019 Jan 7.

KIR and HLA-C Genetic Polymorphisms Influence Plasma IP-10 Concentration in Antiretroviral Therapy-Naive HIV-Infected Adult Zimbabweans.

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1 Department of Chemical Pathology, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.
2 Letten Foundation Research House, Harare, Zimbabwe.
3 Department of Immunology, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.
4 Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
5 Division of Human Genetics, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa.
6 Institute of Clinical Medicine, University of Oslo and Women's Clinic, Rikshospitalet, University Hospital, Oslo, Norway.


Past studies on the relationship between Killer cell Immunoglobulin-like Receptor (KIR) and Human Leukocyte Antigen (HLA) genetic variation and chronic immune activation (CIA) in HIV infection are not uniformly consistent. Moreover, interferon-γ-induced protein 10 (IP-10) is a soluble biomarker of immune activation, with high plasma concentrations predicting accelerated disease progression in HIV infection. Thus, we investigated the association of KIR and HLA-C genetic polymorphisms with plasma IP-10 concentration in 183 treatment-naive chronically HIV-infected adults of Bantu origin from Zimbabwe. KIR genetic variation was determined using allele-specific primer PCR while HLA-C typing was characterized by sequencing. Plasma IP-10 was quantified using enzyme-linked immunosorbent assay. The KIR2DL3 gene was significantly associated with CIA as observed from IP-10 concentrations among KIR2DL3 carriers (265.20 pg/mL, IQR: 179.99-385.19) compared with KIR2DL3 noncarriers (183.56 pg/mL; IQR: 110.98-230.81; p = 0.001) and among KIR2DL3+HLA-C2 carriers (226.23 pg/mL, IQR: 187.96-394.73) compared with KIR2DL3+HLA-C2 noncarriers (212.86 pg/mL, IQR: 160.15-344.99; p = 0.017), respectively. Similarly, IP-10 concentrations were significantly higher (p = 0.030) in the KIR3DS1 carriers (313.86 pg/mL, IQR: 230.05-469.20) compared with KIR3DS1 noncarriers (246.01 pg/mL, IQR: 169.58-373.32). Thus, KIR and HLA-C could be playing important roles in HIV-associated immune activation. The elevation of IP-10 in KIR2DL3 and KIR2DL3+C2 could potentially be explained by increased IFN-γ secretion from activated NK cell activation due to the absence of KIR2DL3's cognate C1 ligand. To the best of our knowledge, this is the first study on a potential link between KIR and HLA-C genetic determinants and plasma IP-10 concentration in this population sample. Future studies are called for in other world populations for biomarkers of disease progression and mechanisms of IP-10 variability in HIV infection.


HIV disease progression; HLA; IP-10; KIR; biomarkers; immune activation


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