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Antiphospholipid antibody-mediated NK cell cytotoxicity

G. Manukyan, E. Kriegova, L. Slavik, Z. Mikulkova, J. Ulehlova, A. Martirosyan, T. Papajik

. 2023 ; 155 (-) : 103791. [pub] 20221230

Language English Country Ireland

Document type Journal Article, Research Support, Non-U.S. Gov't

Antiphospholipid syndrome (APS) is an autoimmune thrombophilia that is characterised by thrombosis and obstetric complications in the presence of antiphospholipid antibodies (aPL). Pregnancy complications remain a challenging problem for patients with APS, especially during the first trimester. Although natural killer (NK) cells constitute up to 70% of decidual lymphocytes during the first trimester, their contribution to early pregnancy loss in APS is largely unknown. We aimed to analyse whether aPL are able to recruit antibody-dependent cellular cytotoxicity (ADCC) of NK cells, with special emphasis on the differences in the effects of aPL containing anti-β2GPI domain 1 (anti-β2GPI-D1) antibodies (aPL+/D1+) and those that do not (aPL+/D1-). Our findings revealed a differential distribution of NK subsets in the presence of different aPL. Namely, aPL+/D1- IgGs increased CD56dim/CD16dim cells, while aPL+/D1 + IgGs increased the number of CD56bright/CD16dim cells. ADCC NK cell cytotoxicity was found to be higher in the presence of aPL+/D1- IgGs, as defined by an increased target cell death, degranulation and increased expression of CD11b, CD69 and NKG2D. Overall, our evidence showed that aPL are able to recruit ADCC, suggesting NK cells as candidate cells for APS-related obstetric complications.

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$a Manukyan, Gayane $u Laboratory of Molecular and Cellular Immunology, Institute of Molecular Biology NAS RA, Yerevan, Armenia; Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. Electronic address: g_manukyan@mb.sci.am
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$a Antiphospholipid syndrome (APS) is an autoimmune thrombophilia that is characterised by thrombosis and obstetric complications in the presence of antiphospholipid antibodies (aPL). Pregnancy complications remain a challenging problem for patients with APS, especially during the first trimester. Although natural killer (NK) cells constitute up to 70% of decidual lymphocytes during the first trimester, their contribution to early pregnancy loss in APS is largely unknown. We aimed to analyse whether aPL are able to recruit antibody-dependent cellular cytotoxicity (ADCC) of NK cells, with special emphasis on the differences in the effects of aPL containing anti-β2GPI domain 1 (anti-β2GPI-D1) antibodies (aPL+/D1+) and those that do not (aPL+/D1-). Our findings revealed a differential distribution of NK subsets in the presence of different aPL. Namely, aPL+/D1- IgGs increased CD56dim/CD16dim cells, while aPL+/D1 + IgGs increased the number of CD56bright/CD16dim cells. ADCC NK cell cytotoxicity was found to be higher in the presence of aPL+/D1- IgGs, as defined by an increased target cell death, degranulation and increased expression of CD11b, CD69 and NKG2D. Overall, our evidence showed that aPL are able to recruit ADCC, suggesting NK cells as candidate cells for APS-related obstetric complications.
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$a Kriegova, Eva $u Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
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$a Slavik, Ludek $u Department of Hemato-oncology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
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$a Mikulkova, Zuzana $u Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
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