Obstetric antiphospholipid syndrome: An approach from glycans of the immunoglobulin G

Abstract

This is a case report of women with pregnancy morbidity (PM), some of them associated with antiphospholipid syndrome (APS), in which the glycan patterns of immunoglobulin G (IgG) were investigated based on the theory of alteration of glycosylation in autoimmunity. We used lectin blot to determine changes in terminal glycosylation of polyclonal IgG from women with antiphospholipid (aPL) antibodies and PM plus vascular thrombosis (PM/VT) and seronegative-obstetric APS (SN-OAPS). In addition, we analyzed IgG from women with PM without aPL (PM/aPL-) and healthy women, as controls. Even though the SN-OAPS and PM/VT groups share the PM, only the SN-OAPS group showed a decreased expression of galactose compared to the healthy group. We also found the presence of mannosylated oligosaccharides in IgG from all patients being significantly higher in IgG from women of the PM/aPL - group. The differences in glycans presented here could relate to pathological mechanisms of PM associated with APS.

Modulation of the activation of endothelial nitric oxide synthase and nitrosative stress biomarkers by aspirin triggered lipoxins: A possible mechanism of action of aspirin in the antiphospholipid syndrome

“…Thrombotic and obstetric APS may correspond to different diseases and may also have different pathogenic mechanisms despite sharing the same aPL 48–50 . Accordingly, we show that nitrosative stress is present mainly in the SN‐OAPS group characterized by increased levels of nitrosative markers, whereas IgG from this group of patients enhanced nitrotyrosine associated with reduced activation of eNOS in HUVECs.…”

“…Because it has been suggested that the pathophysiological mechanisms of vascular APS are different from those of obstetric APS, [48][49][50] in this study we characterize nitrosative stress markers in serum of different clinically relevant groups of APS patients. We also evaluated the potential harmful effects of the polyclonal IgG purified from the serum of women with APS on the expression of nitrotyrosine and activation (i.e., serine 1177 phosphorylation) of eNOS in endothelial cells.…”

Antiphospholipid Antibodies From Women With Pregnancy Morbidity and Vascular Thrombosis Induce Endothelial Mitochondrial Dysfunction, mTOR Activation, and Autophagy

“…IgG from the patient group with clinical features of PM but non-criteria aPL (SN-OAPS) also did not induce any responses in the endothelial cells, thus revealing specific mechanisms triggered by the classical pathological aPL present in patients with PM/VT and VT. We previously showed several in vitro effects induced by aPL from women with PM/VT when compared with aPL from women with PM alone, suggesting that these aPL are distinct and could be triggering other pathways, which leads to different and/or more complex clinical manifestations (Alvarez et al, 2015(Alvarez et al, , 2017. These subtle differences among the mechanisms triggered by aPL subpopulations have been suggested from prior studies (Ripoll et al, 2018;Alvarez et al, 2021). We also highlight that our cellular model was FBS-free, and since we did not performed any recombinant β2GPI addition, it is possible that cellular responses observed here were induced by aCL rather than aB2GPI antibodies.…”