CEACAM2 negatively regulates hemi (ITAM-bearing) GPVI and CLEC-2 pathways and thrombus growth in vitro and in vivo.

Carcinoembryonic antigen-related cell adhesion molecule-2 (CEACAM2) is a cell-surface glycoprotein expressed on blood, epithelial, and vascular cells. CEACAM2 possesses adhesive and signaling properties mediated by immunoreceptor tyrosine-based inhibitory motifs. In this study, we demonstrate that CEACAM2 is expressed on the surface and in intracellular pools of platelets. Functional studies of platelets from Ceacam2(-/-)-deficient mice (Cc2(-/-)) revealed that CEACAM2 serves to negatively regulate collagen glycoprotein VI (platelet) (GPVI)-FcRγ-chain and the C-type lectinlike receptor 2 (CLEC-2) signaling. Cc2(-/-) platelets displayed enhanced GPVI and CLEC-2-selective ligands, collagen-related peptide (CRP), collagen, and rhodocytin (Rhod)-mediated platelet aggregation. They also exhibited increased adhesion on type I collagen, and hyperresponsive CRP and CLEC-2-induced α and dense granule release compared with wild-type platelets. Furthermore, using intravital microscopy to ferric chloride (FeCl3)-injured mesenteric arterioles and laser-induced injury of cremaster muscle arterioles, we herein show that thrombi formed in Cc2(-/-) mice were larger and more stable than wild-type controls in vivo. Thus, CEACAM2 is a novel platelet immunoreceptor that acts as a negative regulator of platelet GPVI-collagen interactions and of ITAM receptor CLEC-2 pathways.

CEACAM2 positively regulates integrin αIIbß3-mediated platelet functions.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is an Ig-ITIM superfamily member that regulates integrin αIIbß3 function. We hypothesized that its twin protein, CEACAM2, exerts a similar physiologic role in murine platelets. CEACAM2-deficient mice (Cc2-/-) displayed prolonged tail bleeding times and increased volume of blood loss. Cc2-/- platelets have moderate integrin αIIbß3-mediated functional defects with impaired kinetics of platelet spreading on fibrinogen and type I collagen and delayed kinetics in the retraction of fibrin clots in vitro. This functional integrin αIIbß3 defect could not be attributed to altered integrin αIIbß3 expression. Cc2-/- platelets displayed normal 'inside-out' signaling properties as demonstrated by normal agonist-induced binding of soluble fluorescein isothiocyanate (FITC)-fibrinogen and JON/A antibody binding. This data provides direct evidence that disruption of CEACAM2 induces a moderate integrin αIIbß3-mediated platelet function defect, and that CEACAM2 is essential to maintain a normal integrin αIIbß3-mediated platelet function.

The Incidences of KEL Blood Group Antigens and Phenotypes in Southwestern Saudi Arabia.

Purpose: Jazan Province in Saudi Arabia is notable for its high prevalence of inherited hemoglobinopathies, including sickle cell disease and thalassemia, necessitating frequent blood transfusions for affected individuals. To mitigate risks such as RBC alloimmunization and hemolytic transfusion reactions, ensuring blood compatibility is crucial. The Kell (KEL) blood group system, pivotal alongside the ABO and RH systems, encompasses multiple antigens implicated in these complications. This study aimed to investigate the frequencies of KEL blood group antigens (K, k, Kpa, and Kpb) and determine KEL phenotypes (K/k and Kpa/Kpb) among Saudi blood donors living in Jazan Province. Methods: A total of 138 anonymous healthy Saudi blood donors from Prince Mohammed bin Nasser Hospital in Jazan Province, Saudi Arabia, were enrolled in this study. Anticoagulated blood was analyzed using the gel card technique to assess K, k, Kpa, and Kpb antigens. Results: The prevalence of KEL antigens was as follows: K (n = 9, 6.52%), k (n = 137, 99.28%), Kpa (n = 1, 0.72%), and Kpb (n = 138, 100%). KEL phenotypes observed were K+k+ (n = 8, 5.80%), K+k- (n = 1 0.72%), K-k+ (n = 129, 93.48%), Kp(a+b+) (n = 1, 0.72%), and Kp(a-b+) (n = 137, 99.28%). Conclusion: This study provides insights into the prevalence of KEL blood group antigens and phenotypes in Jazan Province, Saudi Arabia. These findings may contribute to the establishment of a national blood group database and guide transfusion practices to ensure compatibility and minimize alloimmunization risks.

Lack of association of ABO and RhD blood groups with COVID-19 mortality: A 2-center cross-sectional study in Saudi Arabia.

Several diseases, including both noninfectious diseases and bacterial and viral diseases, are associated with the ABO and RH blood group systems. Previous studies have shown a link between blood type and the probability of coronavirus disease 2019 (COVID-19) infection. In this study, we aimed to explore the correlation between deaths caused by COVID-19 and ABO and RhD blood types in Saudi Arabia. In this cross-sectional observational study, data from COVID-19 patients were collected from 2 major hospitals treating COVID-19 in Riyadh City, Saudi Arabia, between March 2020 and November 2021. The association between ABO and RhD blood types and COVID-19 outcomes was investigated. A total of 2302 real-time polymerase chain reaction-confirmed COVID-19 patients were enrolled in this study; a chi-square test was used to determine the statistical significance of the data. Of the 2302 enrolled patients, 1008 (43.8%) had blood type O, 677 (29.41%) had blood type A, 502 (21.8%) had blood type B, and 115 (5%) had blood type AB. Of the patients, 2143 (93.1%) were RhD-positive. The O-positive blood type had the highest mortality rate among COVID-19-infected patients, whereas the AB-negative type had the lowest. However, statistical analysis revealed no significant correlation between blood type (ABO or RhD) and COVID-19-based susceptibility or mortality. In conclusion, we found no association between ABO and RhD blood types and either susceptibility to or mortality due to COVID-19 in Saudi Arabia.