I am a
Home I AM A Search Login

Papers of the Week

Papers: 13 Jan 2024 - 19 Jan 2024

2024 Jan 17

Blood Adv


Aberrant GPA expression and regulatory function of red blood cells in sickle cell disease.


Marshall JN, Klein MN, Karki P, Promnares K, Setua S, Fan X, Buehler PW, Birukov K, Vasta GR, Fontaine MJ


Glycophorin A (GPA), a red blood cell (RBC) surface glycoprotein, can maintain peripheral blood leukocyte quiescence through interaction with a sialic acid-binding Ig-like lectin (Siglec-9). Under inflammatory conditions such as sickle cell disease (SCD), RBCs’ GPA undergo structural changes affecting this interaction. Peripheral blood samples from SCD patients pre- and post-RBC transfusion were probed for neutrophil and monocyte activation markers and analyzed by FACS; RBCs were purified and tested by FACS for Siglec-9 binding and GPA expression, and incubated ex vivo with cultured endothelial cells to evaluate their effect on barrier function. Activated leukocytes from healthy subjects (HS) were co-incubated with healthy RBCs (RBCH), with GPA-altered RBCs, or with GPA-overexpressing (OE) cells, and analyzed by FACS. Monocyte CD63 and neutrophil CD66b from SCD patients at baseline were increased 47% and 27%, respectively, as compared to HS (p=0.0017, p=0.0162). Post-transfusion, these markers were suppressed by 22% and 17% (p=0.0084, p=0.0633), respectively. GPA expression on RBCSCD was 38% higher (p=0.0291) with decreased Siglec-9 binding compared to RBCH (0.0266). Monocyte CD63 and neutrophil CD66b was suppressed by 26% and 10%, respectively, following incubation with RBCH, (p=0.0464, p=0.0388) and GPA-OE cells, but not with GPA-altered RBCs. Endothelial barrier dysfunction following LPS challenge was restored fully with exposure to RBCH, but not with RBCSCD from patients in pain crisis, nor with RBCH with altered GPA. In conclusion, RBCSCD, prior to transfusion, do not effectively maintain the quiescence of leukocytes and endothelium, but quiescence is restored through RBC transfusion likely by re-established GPA-Siglec-9 interactions.