FcγRIIIa receptor polymorphism influences NK cell mediated ADCC activity against HIV

Talathi, Sneha Pramod; Shaikh, Nawaj; Pandey, Sudhanshu; Saxena, Vandana; Mamulwar, Megha; Thakar, Madhuri

doi:10.1186/s12879-019-4674-z

Cited by 9 publications

(7 citation statements)

References 44 publications

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“…Interestingly, a genotype study showed a functional FCGR3A-V158F polymorphism in ATA-positive patients, suggesting autoantibody-dependent cell-mediated cytotoxicity (ADCC) ( 116 ). This high-affinity FCGR3 polymorphism on ATA-positive patients cells (such as natural killer cells or monocytes) could enhance autoantibody-dependent cell-mediated cytotoxicity (ADCC) or proinflammatory cytokines production in the presence of a low amount of deleterious ATA ( 117 , 118 ). To summarize, TOPO-I is released by endothelial apoptotic cells in the tissue and binds to FB membrane, since TOPO-I has a high affinity for FB membrane.…”

Section: Basic Proof Of Ana Pathogenicity In Ssc and Possible Mechani...mentioning

confidence: 99%

Can Antinuclear Antibodies Have a Pathogenic Role in Systemic Sclerosis?

et al. 2022

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Systemic sclerosis (SSc) is a connective tissue disease characterized by extensive fibrosis of the skin and internal organs, associated with vasculopathy and autoimmune features. Antinuclear antibodies (ANA) are found in almost all SSc patients and constitute strong diagnosis and prognosis biomarkers. However, it remains unclear whether ANA are simple bystanders or if they can have a role in the pathophysiology of the disease. One might think that the nuclear nature of their targets prevents any accessibility to autoantibodies. Nevertheless, recent data suggest that ANA could be pathogenic or at least contribute to the perennation of the disease. We review here first the indirect clues of the contribution of ANA to SSc: they are associated to the disease subtypes, they may precede disease onset, their titer correlates with disease activity and severity, there is an association between molecular subsets, and some patients can respond to B-cell targeting therapy. Then, we describe in a second part the mechanisms of ANA production in SSc from individual genetic background to post-transcriptional modifications of neoantigens. Finally, we elaborate on the potential mechanisms of pathogenicity: ANA could be pathogenic through immune-complex-mediated mechanisms; other processes potentially involve molecular mimicry and ANA penetration into the target cell, with a focus on anti-topoisomerase-I antibodies, which are the most probable candidate to play a role in the pathophysiology of SSc. Finally, we outline some technical and conceptual ways to improve our understanding in this field.

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Section: Basic Proof Of Ana Pathogenicity In Ssc and Possible Mechani...mentioning

confidence: 99%

Can Antinuclear Antibodies Have a Pathogenic Role in Systemic Sclerosis?

et al. 2022

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“…In addition to antibodies, NK cells are one of the primary mediators of ADCC because they express CD16, also known as FcγRIII. The NK-mediated ADCC response has been used as an indicator of HIV suppression, and FcγRIII binding and HIV-specific-ADCC activity can be improved by the administration of monoclonal antibodies that are regulated by single nucleotide polymorphisms (SNPs) ( 78 ).…”

Section: Enhancing Nk Cell Function In Hiv-1 Infectionmentioning

confidence: 99%

Targeting NK Cells for HIV-1 Treatment and Reservoir Clearance

Duan

Liu

2022

Front. Immunol.

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Combined antiretroviral therapy (cART) can inhibit the replication of human immunodeficiency virus type 1 (HIV-1) and reduce viral loads in the peripheral blood to undetectable levels. However, the presence of latent HIV-1 reservoirs prevents complete HIV-1 eradication. Several drugs and strategies targeting T cells are now in clinical trials, but their effectiveness in reducing viral reservoirs has been mixed. Interestingly, innate immune natural killer (NK) cells, which are promising targets for cancer therapy, also play an important role in HIV-1 infection. NK cells are a unique innate cell population with features of adaptive immunity that can regulate adaptive and innate immune cell populations; therefore, they can be exploited for HIV-1 immunotherapy and reservoir eradication. In this review, we highlight immunotherapy strategies for HIV infection that utilize the beneficial properties of NK cells.

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“…A recent study showed that HIV-1 patients with homozygous 176V for the FcγRIIIa-V176F (rs396991) polymorphisms and/or Y158H (rs396716) genotypes have higher HIV-1 specific ADCC response ( 49 ). It was hypothesized that the V176F polymorphism improves the binding capacity between the Fc receptor and anti-HIV-1 antibody, indicating that the FcγRIIIa receptor expressed on NK cells induced strong ADCC response for viral clearance ( 63 , 64 ).…”

Section: Fcγr Polymorphisms and The Risk Of Hiv-1 Infection With And Without Vaccinesmentioning

confidence: 99%

“…These antibodies were associated with higher Fc polyfunctionality early in the course of infection ( 146 ). Furthermore, FcγRIIIa-V176F (rs396991) and FcγRIIIa-Y158H (rs396716) polymorphism are associated with enhanced ADCC in HIV-1 patients ( 49 ), giving the indication that the expression of FcγRIIIa receptor on NK cells led to the induction of strong ADCC response for viral clearance ( 63 , 64 ). These studies suggest that bNAbs have potential as therapeutic or prophylactic treatment in humans.…”

Section: Fcγrs Broadly Neutralizing Antibodies and Hiv-1 Remission Attemptsmentioning

confidence: 99%

Are Fc Gamma Receptor Polymorphisms Important in HIV-1 Infection Outcomes and Latent Reservoir Size?

et al. 2021

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Fc gamma receptors (FcγR) are cell surface glycoproteins which trigger specific effector-cell responses when cross-linked with the Fc portions of immunoglobulin (IgG) antibodies. During HIV-1 infection, the course of disease progression, ART response, and viral reservoir size vary in different individuals. Several factors may account for these differences; however, Fc gamma receptor gene polymorphisms, which influence receptor binding to IgG antibodies, are likely to play a key role. FcγRIIa (CD32) was recently reported as a potential marker for latent HIV reservoir, however, this assertion is still inconclusive. Whether FcγR polymorphisms influence the size of the viral reservoir, remains an important question in HIV cure studies. In addition, potential cure or viral suppression methods such as broadly neutralizing antibody (bNAbs) may depend on FcγRs to control the virus. Here, we discuss the current evidence on the potential role played by FcγR polymorphisms in HIV-1 infection, treatment and vaccine trial outcomes. Importantly, we highlight contrasting findings that may be due to multiple factors and the relatively limited data from African populations. We recommend further studies especially in sub-Saharan Africa to confirm the role of FcγRIIa in the establishment of latent reservoir and to determine their influence in therapies involving bNAbs.

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FcγRIIIa receptor polymorphism influences NK cell mediated ADCC activity against HIV

Cited by 9 publications

References 44 publications

Can Antinuclear Antibodies Have a Pathogenic Role in Systemic Sclerosis?

Can Antinuclear Antibodies Have a Pathogenic Role in Systemic Sclerosis?

Targeting NK Cells for HIV-1 Treatment and Reservoir Clearance

Are Fc Gamma Receptor Polymorphisms Important in HIV-1 Infection Outcomes and Latent Reservoir Size?

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