Antiphospholipid antibody-mediated NK cell cytotoxicity

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 antiB2GPI domain 1 (anti-beta 2GPI-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 CD56(dim)/CD16(dim) 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.

Automated summary

Antiphospholipid syndrome (APS) is an autoimmune thrombophilia characterized by thrombosis and obstetric complications in the presence of antiphospholipid antibodies (aPL). Our study aimed to investigate the role of natural killer (NK) cells in early pregnancy loss in APS. We found that aPL can recruit antibody-dependent cellular cytotoxicity (ADCC) of NK cells, with differences observed between aPL containing antiB2GPI domain 1 (anti-beta 2GPI-D1) antibodies (aPL+/D1+) and those that do not (aPL+/D1-). This suggests that NK cells may play a role in APS-related obstetric complications.