Previous work from MI and others has shown that sex and cytomegalovirus (CMV) serostatus are key drivers of variation in the human immune response. The overall aim of the MI study is greater understanding of the determinants of variation in the immune responsiveness of healthy adult humans. The Milieu Interieur (MI) study is comprised of a cohort of 1000 healthy individuals, stratified by age (20–69, n = 200 per decade) and sex (500 males and 500 females). A major challenge in determining potential effects of RhD status on antiviral immunity is the lack of large, relevant human cohort studies with the power to detect potentially subtle immune differences. RhD negativity varies substantially across different populations and may potentially confer an as yet unknown fitness advantage. RhD status also appears to affect susceptibility to SARS-CoV-2 in a study of 14,112 donors, RhD-negative individuals had a lower risk of initial infection, intubation and death- suggesting a protective role for RhD negativity.

RhD-negative individuals also appear to be protected against certain infections, including latent toxoplasmosis. Several studies have demonstrated that RhD-positive and -negative subjects differ in resistance to the pathological effects of aging, fatigue, and smoking. An agnostic analysis of 1217 disease states found an association between RhD status and hypertension during pregnancy.

Īlthough less well studied, RhD status is also known to influence several other health outcomes. RhD-negative women can also be sensitised during pregnancy with an RhD-positive foetus or during delivery, often leading to haemolytic disease of the new born in subsequent pregnancies with RhD-positive foetuses. The Rhesus protein is highly immunogenic and resulting antibodies can induce severe adverse reactions in RhD-negative individuals should they encounter the D antigen following an unmatched blood transfusion. The function of the RhD antigen is largely unknown, although it may play a role in maintaining erythrocyte membrane integrity or transport of ammonium and carbon dioxide. RhD status is determined based on the presence or absence of the Rhesus antigen, a transmembrane protein found on the surface of red blood cells. The Rhesus D blood group antigen (RhD) system is an important clinical factor in transfusion and obstetric medicine. This amplified IFNγ signalling axis may explain the increased viral resistance previously described in RhD-negative individuals. Further investigation, using gene set enrichment analysis, revealed enhanced IFNγ signalling in RhD-negative males. Interestingly these Rhesus-associated differences were not seen in females. However, upon sex-specific analysis, we observed over 40 differentially expressed genes (DEGs) between RhD-positive ( n = 384) and RhD-negative males ( n = 75) after influenza virus stimulation. Using regression analysis, we observed no significant differences in responses to polyIC or LPS between RhD-positive and -negative individuals. Whole blood was stimulated with LPS, polyIC, and the live influenza A virus and the NanoString human immunology panel of 560 genes used to assess donor immune response and to investigate sex-specific effects. We used the rs590787 SNP in the RHD gene to classify the 1000 donors as either RhD-positive or -negative. Here, we used transcriptomic and genomic data from the Milieu Interieur cohort of 1000 healthy individuals to explore the effect of Rhesus status on the immune response. However, potential mechanisms contributing to these associations have not yet been defined.

Reports suggest that RhD-negative individuals are better protected against infectious diseases and have overall better health. The Rhesus D antigen (RhD) has been associated with susceptibility to several viral infections.

Rh negative man and reproduction