The natural killer cell‐associated rs9916629<i>‐</i>C allele is a novel genetic risk factor for fatal COVID‐19

Vietzen, Hannes; Furlano, Philippe L.; Traugott, Marianna; Totschnig, David; Hoepler, Wolfgang; Straßl, Robert; Zoufaly, Alexander; Puchhammer‐Stöckl, Elisabeth

doi:10.1002/jmv.28404

Cited by 9 publications

(4 citation statements)

References 23 publications

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“…KLRK1 LNK/HNK variants (rs1049174) associated with NKG2D activity were identified using the TaqMan SNP Genotyping Assay and TaqMan Universal PCR Master Mix (Thermo Fisher Scientific, Waltham, MA, United States). Lastly, the functionally relevant rs9916629-C/T polymorphism was examined via an in-house TaqMan assay [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

Natural Killer Cell Presence in Antibody-Mediated Rejection

Diebold,

Farkash,

Barnes

et al. 2024

Transpl Int

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Transcript analyses highlight an important contribution of natural killer (NK) cells to microvascular inflammation (MVI) in antibody-mediated rejection (ABMR), but only few immunohistologic studies have quantified their spatial distribution within graft tissue. This study included 86 kidney transplant recipients who underwent allograft biopsies for a positive donor-specific antibody (DSA) result. NK cells were visualized and quantified within glomeruli and peritubular capillaries (PTC), using immunohistochemistry for CD34 alongside CD16/T-bet double-staining. Staining results were analyzed in relation to histomorphology, microarray analysis utilizing the Molecular Microscope Diagnostic System, functional NK cell genetics, and clinical outcomes. The number of NK cells in glomeruli per mm2 glomerular area (NKglom) and PTC per mm2 cortical area (NKPTC) was substantially higher in biopsies with ABMR compared to those without rejection, and correlated with MVI scores (NKglom Spearman’s correlation coefficient [SCC] = 0.55, p < 0.001, NKPTC 0.69, p < 0.001). In parallel, NK cell counts correlated with molecular classifiers reflecting ABMR activity (ABMRprob: NKglom 0.59, NKPTC 0.75) and showed a trend towards higher levels in association with high functional FCGR3A and KLRC2 gene variants. Only NKPTC showed a marginally significant association with allograft function and survival. Our immunohistochemical results support the abundance of NK cells in DSA-positive ABMR.

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Section: Methodsmentioning

confidence: 99%

Natural Killer Cell Presence in Antibody-Mediated Rejection

Diebold,

Farkash,

Barnes

et al. 2024

Transpl Int

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“…HLA‐E genotyping was performed using a previously published TaqMan protocol, with primers and probes as described in detail earlier 24 . The rs9916629 C/T variants were determined using an in‐house TaqMan assay 25 . The rs9916629 and HLA‐E TaqMan assays were performed with the Luna Universal Probe qPCR Master Mix (NEB Biolabs) as recommended by the manufacturers.…”

Section: Methodsmentioning

confidence: 99%

“…24 The rs9916629 C/T variants were determined using an in-house TaqMan assay. 25 The rs9916629 and HLA-E TaqMan assays were performed with the Luna Universal Probe qPCR Master Mix (NEB Biolabs) as recommended by the manufacturers.…”

Section: Genotypingmentioning

confidence: 99%

Association between human genetic variants affecting the host NK cell response and the development of herpes simplex virus type 1 encephalitis

Graninger

Vietzen

Puchhammer‐Stöckl

2023

Journal of Medical Virology

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Herpes simplex virus encephalitis (HSE) is a rare complication of herpes simplex virus type 1 (HSV-1) infection or reactivation. It is so far unclear why only few patients develop HSE. As natural killer (NK) cells provide an important defense against HSV-1, we investigated whether there is an association between distinct human genetic variants associated with the host NK cell response and HSE. Forty-nine adult patients with confirmed HSE and 247 matched controls were analyzed for the distribution of the following genotypes: CD16A (FcγRIIIA) V/F and IGHG1 G1m3/17, both influencing antibody-dependent cellular cytotoxicity; HLA-E*0101/*0103, associated with NK cell activation; and SLFN13 rs9916629 C/T associated with NK cell response. Homozygous HLA-E*0101:0101 and HLA-E*0103:0103 variants as well as the rs9916629 CC genotype were overrepresented in HSE patients compared to controls (p ≤ 0.001). Notably, cooccurrence of the homozygous HLA-E*0101 and rs9916629 CC genotypes was present in 19% of patients but totally absent in controls (p ≤ 0.0001). Distribution of CD16A and IGHG1 variants did not differ between patients and controls. Our data show that the rare combination of HLA-E*0101:0101 and rs9916629 CC is significantly associated with HSE. Possibly, these genetic variations could be useful as clinical markers predicting HSE prognosis and helping to adapt the treatment of HSE in the individual patient.

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Section: Kir Typing For Missing Self Calculation and Functional Singl...mentioning

confidence: 99%

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The natural killer cell‐associated rs9916629‐C allele is a novel genetic risk factor for fatal COVID‐19

Cited by 9 publications

References 23 publications

Natural Killer Cell Presence in Antibody-Mediated Rejection

Natural Killer Cell Presence in Antibody-Mediated Rejection

Association between human genetic variants affecting the host NK cell response and the development of herpes simplex virus type 1 encephalitis

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