KIR-HLA clase i y tuberculosis pulmonar en población amerindia del Chaco, Argentina

Sorrentino, Alicia Habegger de; Pardo, R; Marinic, Karina; Duarte, Sonia C.; Lotero, Carlos

doi:10.1016/j.eimc.2013.10.007

Cited by 3 publications

(3 citation statements)

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“…Previous studies have shown that different levels of susceptibility to M. tuberculosis may be due to variations in KIR receptors and, consequently, in the repertoire of NK cells [87][88][89]. In the context of TB, a higher prevalence of KIR2DL3 among TB patients has been observed in several studies [15,18,90,91]. Biberg-Salum et al [92] showed that HLA-C * 07 allele conferred protection against the development of cytomegalovirus retinitis in Brazilian AIDS patients.…”

Section: Discussionmentioning

confidence: 99%

“…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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…This was confirmed in a study of Brazilian SSc patients [ 6 ]. HLAB*35 was also associated with SSc in a Choctaw Indian tribe with increased prevalence of SSc [ 7 ]. Furthermore, the association between HLA-B*35 and various other disorders as well as severe viral infections has been reported [ 6 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients

et al. 2015

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IntroductionHLA-B*35 is associated with increased risk of developing pulmonary hypertension in SSc patients. We previously reported that HLA-B*35 induces endothelial cell dysfunction via activation of ER stress/UPR and upregulation of the inflammatory response. Because PBMCs from lcSSc-PAH patients are also characterized by activation of ER stress/UPR and inflammation, the goal of this study was to assess whether the presence of HLA-B*35 contributes to those characteristics.MethodsPBMCs were purified from healthy controls (n = 49 HC) and lcSSc patients, (n = 44 with PAH, n = 53 without PAH). PBMCs from each group were stratified for the presence of HLA-B*35. Global changes in gene expression in response to HLA-B*35, HLA-B*8 or empty lentivirus were investigated by microarray analysis in HC PBMCs. Total RNA was extracted and qPCR was performed to measure gene expression.ResultsER stress markers, in particular the chaperones BiP and DNAJB1 were significantly elevated in PBMC samples carrying the HLA-B*35 allele. IL-6 expression was also significantly increased in HLA-B*35 lcSSc PBMCs and positively correlated with ER stress markers. Likewise, HMGB1 was increased in HLA-B*35-positive lcSSc PBMCs. Global gene expression analysis was used to further probe the role of HLA-B*35. Among genes downregulated by HLA-B*35 lentivirus were genes related to complement (C1QB, C1QC), cell cycle (CDNK1A) and apoptosis (Bax, Gadd45). Interestingly, complement genes (C1QC and C1QB) showed elevated expression in lcSSc without PAH, but were expressed at the low levels in lcSSc-PAH. The presence of HLA-B*35 correlated with the decreased expression of the complement genes. Furthermore, HLA-B*35 correlated with decreased expression of cyclin inhibitors (p21, p57) and pro-apoptotic genes (Bax, Gadd45) in lcSSc B35 subjects. FYN, a tyrosine kinase involved in proliferation of immune cells, was among the genes that were positively regulated by HLA-B*35. HLA-B*35 correlated with increased levels of FYN in lcSSc PBMCs.ConclusionsOur study demonstrates that HLA-B*35 contributes to the dysregulated expression of selected ER stress, inflammation and proliferation related genes in lcSSc patient PBMCs, as well as healthy individuals, thus supporting a pathogenic role of HLA-B*35 in the development of PAH in SSc patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0881-1) contains supplementary material, which is available to authorized users.

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The role of human host genetics in tuberculosis resistance

Kinnear

Hoal

Schurz

et al. 2017

Expert Review of Respiratory Medicine

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Tuberculosis (TB) remains a public health problem: the latest estimate of new incident cases per year is a staggering 10.4 million. Despite this overwhelming number, the majority of the immunocompetent population can control infection with Mycobacterium tuberculosis. The human genome underlies the immune response and contributes to the outcome of TB infection. Areas covered: Investigations of TB resistance in the general population have closely mirrored those of other infectious diseases and initially involved epidemiological observations. Linkage and association studies, including studies of VDR, SLC11A1 and HLA-DRB1 followed. Genome-wide association studies of common variants, not necessarily sufficient for disease, became possible after technological advancements. Other approaches involved the identification of those individuals with rare disease-causing mutations that strongly predispose to TB, epistasis and the role of ethnicity in disease. Despite these efforts, infection outcome, on an individual basis, cannot yet be predicted. Expert commentary: The early identification of future disease progressors is necessary to stem the TB epidemic. Human genetics may contribute to this endeavour and could in future suggest pathways to target for disease prevention. This will however require concerted efforts to establish large, well-phenotyped cohorts from different ethnicities, improved genomic resources and a better understanding of the human genome architecture.

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KIR-HLA clase i y tuberculosis pulmonar en población amerindia del Chaco, Argentina

Cited by 3 publications

References 24 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

The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients

The role of human host genetics in tuberculosis resistance

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