Association between KIR genotypes and HLA-B alleles on viral load in Southern Brazilian individuals infected by HIV-1 subtypes B and C

Fernandes-Cardoso, Juliana; Suffert, Theodoro A; Correa, M; Jobim, Luiz Fernando Job; Jobim, Mariana; Salim, Patrícia Hartstein; Arruda, Monica Barcelos; Boullosa, Lídia Theodoro; Tanuri, Amílcar; Pôrto, Luís Cristóvão; Ferreira, Orlando C.

doi:10.1016/j.humimm.2016.06.013

Cited by 3 publications

(6 citation statements)

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“…In the present study, we examined the distribution of HLA-B, HLA-C, and KIR genes in TB and/or HIVinfected patients and investigated the putative role of these genes in the occurrence of TB/HIV-IRIS. The individuals included in the present study had their HLA-B, HLA-C, and KIR genes determined, and the frequency data observed corroborated what has been described for the HIV-1-infected population [12,69] and the general Brazilian population [70][71][72][73][74][75]. HLA-B*08 and female gender were associated with protection against TB onset in the studied population.…”

Section: Discussionsupporting

confidence: 88%

“…The growing interest in the role of host genetic factors in the dynamics of infectious diseases is at least in part fueled by the possibility of finding predictive biomarkers of disease outcomes, such as the occurrence of IRIS in TB-HIV co-infected individuals, contributing to improving clinical management in an attempt to avoid severe disease complications. Several reports have associated polymorphic genes with infectious diseases in different populations and ethnic groups [5,7,12,60,61]. Host genetic factors have been consistently linked to variations in both susceptibility and resistance to HIV-1 infection and TB [7,15,62,63].…”

Section: Discussionmentioning

confidence: 99%

“…A total of 14 KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, and 3DS1) and 2 KIR pseudogenes (2DP1 and 3DP1) were screened using this approach. KIR group genotype nomenclature was designated according to the current working definition, which characterizes genotypes AA and Bx based on the combinations of haplotype A (absence of all the activating genes, except KIR2DS4) and haplotype B (presence of one or more of the activating genes) [12,56]. We also classified KIR genotypes by the ID assigned by the Allele Frequency Net Database (http://www.allelefrequencies.net).…”

Section: Kir Genotypingmentioning

confidence: 99%

“…HLA-C has a dual role of presenting antigens to CTL and serving as ligands to KIR receptors on NK cells, thus regulating the lysis of target cells mediated by NK cells [10]. Many KIR genes and KIR-HLA-B/KIR-HLA-C pairs have been associated with distinct outcomes in the context of HIV-1 infection [6,[11][12][13][14]. In the same way, genetic studies involving protection or susceptibility to pulmonary tuberculosis have also highlighted the role of HLA-B and KIR genes, as well as KIR + HLA-C pairs [5,[15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Clinical and genetic markers associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

et al. 2020

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Background: Tuberculosis (TB) and AIDS are the leading causes of infectious disease death worldwide. In some TB-HIV co-infected individuals treated for both diseases simultaneously, a pathological inflammatory reaction termed immune reconstitution inflammatory syndrome (IRIS) may occur. The risk factors for IRIS are not fully defined. We investigated the association of HLA-B, HLA-C, and KIR genotypes with TB, HIV-1 infection, and IRIS onset. Methods: Patients were divided into four groups: Group 1-TB+/HIV+ (n = 88; 11 of them with IRIS), Group 2-HIV+ (n = 24), Group 3-TB+ (n = 24) and Group 4-healthy volunteers (n = 26). Patients were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. The HLA-B and HLA-C loci were typed using SBT, NGS, and KIR genes by PCR-SSP. Unconditional logistic regression models were performed for Protection/risk estimation. Results: Among the individuals with TB as the outcome, KIR2DS2 was associated with increased risk for TB onset (aOR = 2.39, P = 0.04), whereas HLA-B*08 and female gender were associated with protection against TB onset (aOR = 0.23, P = 0.03, and aOR = 0.33, P = 0.01, respectively). Not carrying KIR2DL3 (aOR = 0.18, P = 0.03) and carrying HLA-C*07 (aOR = 0.32, P = 0.04) were associated with protection against TB onset among HIV-infected patients. An increased risk for IRIS onset was associated with having a CD8 count ≤500 cells/mm 3 (aOR = 18.23, P = 0.016); carrying the KIR2DS2 gene (aOR = 27.22, P = 0.032), the HLA-B*41 allele (aOR = 68.84, P = 0.033), the KIR2DS1 + HLA-C2 pair (aOR = 28.58, P = 0.024); and not carrying the KIR2DL3 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), and the KIR2DL1 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), Conclusions: These results suggest the participation of these genes in the immunopathogenic mechanisms related to the conditions studied. This is the first study demonstrating an association of HLA-B*41, KIR2DS2, and KIR + HLA-C pairs with IRIS onset among TB-HIV co-infected individuals.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Kir Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical and genetic markers associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

et al. 2020

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“…KIR2DL5 has already been associated with a reduced risk of HIV-1 infection and reduced HIV-1 transmission among Africans (Jennes et al, 2006;Omosun et al, 2018), but there is no previous report associating this allele with virological control. The KIR2DS1 gene bind HLA-C molecules of the C2 group (Folley et al, 2008). It has already been significantly associated with a lower viral load in HIV-1 patients from India (Chavan et al, 2014) and South Africa (Wong et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Killer immunoglobulin-like receptor (KIR) genes are associated with the risk of episodes of high-level and detectable viremia among HIV controllers

et al. 2021

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Background: HIV controllers (HICs) constitute a heterogeneous group of HIV-1 individuals able to suppress plasma viremia to low or undetectable levels in the absence of antiretroviral therapy. Host genetic factors may be involved in the sustained control of viral replication observed. We investigated the distribution and the potential impact of human leukocyte antigens (HLA)-B and -C alleles, killer immunoglobulin-like receptor (KIR) genes, single nucleotide polymorphisms (SNPs) of the NLRP3, CARD8 and IL-1β inflammasome genes, and CCR5Δ32 mutation on the viral control among HICs. Methods: In total, 28 HICs were categorized as persistent elite controllers (PECs, n = 7), ebbing elite controllers (EECs, n = 7), and viremic controllers (VCs, n = 14) according to the level of natural suppression of viremia. HLA alleles were assigned by sequencing-based typing, KIR alleles by polymerase chain reaction (PCR) sequence-specific amplification, SNPs by real-time PCR, and the CCR5Δ32 mutation by PCR. Results: Significant differences were observed in the pairwise comparisons of protective HLA-B alleles, KIR Bx genotype, KIR2DL3 + C1 pair, KIR2DL5, and KIR2DS5 allelic carrier frequencies among the HIC groups. Multivariate models showed that HICs without the KIR2DL3 allele or without KIR2DL3 + C1/C2 pair, with the HLA-C*08 allele or with the NLRP3 rs10754558-G SNP had a higher mean hazard of a viral load above 2,000 copies/mL, while a lower mean hazard of this event was observed for HICs with KIR2DL5, KIR2DS1, KIR2DS5, and KIR3DS1 alleles. Moreover, HICs with the KIR2DS5 allele had less risk of undergoing viral load (VL) blips within the same normalized period than those participants without this allele, while HICs without the KIR2DL3 allele had a mean higher risk of experiencing VL blips. Conclusions: These results indicate that innate immune mechanisms may play an essential role in modulating the sustained control of viral replication in HICs.

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Immunogenetics of MHC and KIR in the Leprosy

Alves¹,

Tiyo²,

Sell³

et al. 2019

Hansen's Disease - The Forgotten and Neglected Disease

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Several genetic polymorphisms in immune response genes have been associated to leprosy. This fact converges on the main hypothesis that genetic factors are involved in the disease susceptibility in two distinct steps: leprosy per se and their clinical forms. These genes play an important role in the recognition process, in the activation of the main metabolic pathway of the immune response and in the evolution of the disease. The scope of this project was to highlight the role of the immune response genes in the context of leprosy, emphasizing the participation of some of them in the signaling and targeting processes in response to bacillus infection and on disease evolution, such as HLA, KIR and MIC genes. Some environmental and genetic factors are important when the exposure to the bacillus occurs, leading to cure or not. Factors that favor a cellular or humoral immune response may influence the clinical manifestations after the infection inducting to one of extreme poles. Furthermore, some genetic factors were associated to the type of reaction that some individuals present during the disease development. Thus, it is very important to highlight the participation of some genetic factors in the immunopathogenesis of leprosy.

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Association between KIR genotypes and HLA-B alleles on viral load in Southern Brazilian individuals infected by HIV-1 subtypes B and C

Cited by 3 publications

References 47 publications

Clinical and genetic markers associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

Clinical and genetic markers associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

Killer immunoglobulin-like receptor (KIR) genes are associated with the risk of episodes of high-level and detectable viremia among HIV controllers

Immunogenetics of MHC and KIR in the Leprosy

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