Ocular toxoplasmosis: susceptibility in respect to the genes encoding the KIR receptors and their HLA class I ligands

Ayo, Christiane Maria; Frederico, Fábio Batista; Siqueira, Rubens Camargo; Mattos, Cinara Cássia Brandão de; Previato, Mariana; Barbosa, Amanda Pires; Murata, Fernando Henrique Antunes; Silveira-Carvalho, Aparecida Perpétuo; Mattos, Luiz Carlos de

doi:10.1038/srep36632

Cited by 16 publications

(7 citation statements)

References 56 publications

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“…If a given HLA association is attributable to NK cells rather than CD8 + T cells, then other HLA class I molecules with similar KIR-binding properties should be similarly protective/detrimental (in the context of the relevant KIRs). This pretext forms the basis of classical KIR-HLA analyses (30)(31)(32)(33). We investigated this possibility for each of the HLA class I alleles included in this study (HLA-B*57 and HLA-B*35Px in the HIV-1infected (Functional KIR3DS1-) IAVI cohort; HLA-A*02:07, HLA-C*08, and HLA-B*54 in the HTLV-1-infected Kagoshima cohort; and HLA-B*57 in the HCV-infected cohort).…”

Section: Primary Hla Class I Associations Are Unlikely To Be Attribut...mentioning

confidence: 99%

Inhibitory killer cell immunoglobulin-like receptors strengthen CD8 ⁺ T cell–mediated control of HIV-1, HCV, and HTLV-1

et al. 2018

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Killer-cell immunoglobulin-like receptors (KIRs) are expressed predominantly on natural killer cells, where they play a key role in the regulation of innate immune responses. Recent studies show that inhibitory KIRs can also impact adaptive T cell-mediated immunity. In mice and in human T cells in vitro, inhibitory KIR ligation enhanced CD8+ T cell survival. To investigate the clinical relevance of these observations, we conducted an extensive immunogenetic analysis of multiple, independent cohorts of HIV-1, hepatitis C virus (HCV) and human T cell leukemia virus (HTLV-1)-infected individuals in conjunction with in vitro assays of T cell survival, analysis of ex vivo KIR expression and mathematical modeling of host-virus dynamics. Our data suggest that functional engagement of inhibitory KIRs enhances the CD8+ T cell response against HIV-1, HCV and HTLV-1 and is a significant determinant of clinical outcome in all three viral infections.

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Section: Primary Hla Class I Associations Are Unlikely To Be Attribut...mentioning

confidence: 99%

Inhibitory killer cell immunoglobulin-like receptors strengthen CD8 ⁺ T cell–mediated control of HIV-1, HCV, and HTLV-1

et al. 2018

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“…Likewise, the TNF-α gene polymorphism (2308G/A) do not seem to be associated with OT development and recurrences [ 58 ]. Similarly, Ayo et al found that the presence of the -KIR3DS1/KIR3DL1+/Bw4-8-80Ile+ combination was a protective factor against recurrences (OR: 0.13; 95% CI 0.03–0.45) [ 74 ].…”

Section: Resultsmentioning

confidence: 99%

Risk factors for recurrences and visual impairment in patients with ocular toxoplasmosis: A systematic review and meta-analysis

et al. 2023

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Background Ocular toxoplasmosis (OT) is caused by the parasite Toxoplasma gondii. OT is the leading cause of posterior uveitis globally; it is a recurrent disease that may result in visual impairment and blindness. This systematic review and meta-analysis aim to summarize and evaluate the risk factors for recurrences, visual impairment, and blindness described in the literature worldwide. Methods and findings We performed a systematic literature search in PubMed, Embase, VHL, Cochrane Library, Scopus, and DANS EASY Archive. All studies reporting patients with clinically and serologically confirmed OT presenting any clinical or paraclinical factor influencing recurrences, visual impairment, and blindness were included. Studies presenting secondary data, case reports, and case series were excluded. An initial selection was made by title and abstract, and then the studies were reviewed by full text where the eligible studies were selected. Then, the risk of bias was assessed through validated tools. Data were extracted using a validated extraction format. Qualitative synthesis and quantitative analysis were done. This study was registered on PROSPERO (CRD42022327836). Results Seventy two studies met the inclusion criteria. Fifty-three were summarized in the qualitative synthesis in three sections: clinical and environmental factors, parasite and host factors, and treatment-related factors. Of the 72 articles, 39 were included in the meta-analysis, of which 14 were conducted in South America, 13 in Europe, four in Asia, three multinational, two in North America and Central America, respectively, and only one in Africa. A total of 4,200 patients with OT were analyzed, mean age ranged from 7.3 to 65.1 year of age, with similar distribution by sex. The frequency of recurrences in patients with OT was 49% (95% CI 40%–58%), being more frequent in the South American population than in Europeans. Additionally, visual impairment was presented in 35% (95% CI 25%–48%) and blindness in 20% (95% CI 13%–30%) of eyes, with a similar predominance in South Americans than in Europeans. On the other hand, having lesions near the macula or adjacent to the optic nerve had an OR of 4.83 (95% CI; 2.72–8.59) for blindness, similar to having more than one recurrence that had an OR of 3.18 (95% CI; 1.59–6.38). Finally, the prophylactic therapy with Trimethoprim/Sulfamethoxazole versus the placebo showed a protective factor of 83% during the first year and 87% in the second year after treatment. Conclusion Our Systematic Review showed that clinical factors such as being older than 40 years, patients with de novo OT lesions or with less than one year after the first episode, macular area involvement, lesions greater than 1 disc diameter, congenital toxoplasmosis, and bilateral compromise had more risk of recurrences. Also, environmental and parasite factors such as precipitations, geographical region where the infection is acquired, and more virulent strains confer greater risk of recurrences. Therefore, patients with the above mentioned clinical, environmental, and parasite factors could benefit from using prophylactic therapy.

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“…To analyze the influence of KIR with their respective ligands, patients and controls were classified into groups according to their HLA ligands: HLA-A3 or A11, HLA-Bw4 (Bw4-80Ile and Bw4-80Thr) (20,21) and HLA-C ligand of the C1 or C2 group. (22) The KIR haplotype groups (AA, Bx) and genotype ID were obtained from the Allele Frequency Net Database (http://www.allelefrequencies.…”

Section: Discussionmentioning

confidence: 99%

Influence of KIR in the HIV-1/AIDS disease in the North/Northwest region of Paraná State, Brazil.

Lara-Armi¹,

Visentainer²,

Sell³

et al. 2022

JHS

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Introduction:The aim of this study was to investigate NK cell count and the association of KIR, HLA Class I and KIR-HLA ligands with HIV infection and progression to AIDS. Methods: A total of 99 blood samples were collected from HIV-1 patients and 99 for the control group. The quantification of NK cells was performed by flow cytometry and the definition of the KIR and HLA genes was performed by PCR-SSOr. HLA Class I allele and haplotype frequencies were obtained using Arlequin software, and gene, genotype and haplotype frequencies of KIR and KIR-HLA ligands were obtained by direct counting. Statistical analyses were conducted using Chi-square test with Yates correction or Fisher's exact test for categorical variables and the Mann-Whitney test for continuous variables. Results: The NK cells count was lower in HIV group compared to controls. HLA-A*68:02 allele was associated to susceptibility to HIV infection, and HLA-A*23:01 and HLA-A*32:01 were protective factor for HIV infection and for AIDS progression, respectively. The KIR3DL1-Bw4-80Ilehmz ligand and only the Bw4-80Ilehmz ligand group were associated to HIV infection. KIR2DS3/2DL3/C1 and the combination of inhibitory KIR2DL3-C1/3DL2-A3/A11 showed protection to HIV infection. Conclusions: The HIV infection interfered with NK cell count. In addition, our results confirmed HLA class I associations with HIV infection and AIDS progression, and suggest the influence of activating and inhibitory KIRs and its HLA class I ligands on course of HIV infection.

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Ocular toxoplasmosis: susceptibility in respect to the genes encoding the KIR receptors and their HLA class I ligands

Cited by 16 publications

References 56 publications

Inhibitory killer cell immunoglobulin-like receptors strengthen CD8 ⁺ T cell–mediated control of HIV-1, HCV, and HTLV-1

Inhibitory killer cell immunoglobulin-like receptors strengthen CD8 ⁺ T cell–mediated control of HIV-1, HCV, and HTLV-1

Risk factors for recurrences and visual impairment in patients with ocular toxoplasmosis: A systematic review and meta-analysis

Influence of KIR in the HIV-1/AIDS disease in the North/Northwest region of Paraná State, Brazil.

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Ocular toxoplasmosis: susceptibility in respect to the genes encoding the KIR receptors and their HLA class I ligands

Cited by 16 publications

References 56 publications

Inhibitory killer cell immunoglobulin-like receptors strengthen CD8 + T cell–mediated control of HIV-1, HCV, and HTLV-1

Inhibitory killer cell immunoglobulin-like receptors strengthen CD8 + T cell–mediated control of HIV-1, HCV, and HTLV-1

Risk factors for recurrences and visual impairment in patients with ocular toxoplasmosis: A systematic review and meta-analysis

Influence of KIR in the HIV-1/AIDS disease in the North/Northwest region of Paraná State, Brazil.

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Product

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Inhibitory killer cell immunoglobulin-like receptors strengthen CD8 ⁺ T cell–mediated control of HIV-1, HCV, and HTLV-1

Inhibitory killer cell immunoglobulin-like receptors strengthen CD8 ⁺ T cell–mediated control of HIV-1, HCV, and HTLV-1