Rhesus D Variants among Pregnant Women in the Northern Nigeria

CHAPTER ONE

INTRODUCTION

• BACKGROUND

The Rhesus blood group system is one of the most polymorphic and immunogenic systems of blood group antigens known in humans. This blood group system is comprise of numerous antigens, principally among them is ‘’RHD’’, ‘’RhC’’, “Rhc”, “RhE” and “Rhe” antigens (Flegel, 2007; Sell et al., 2013).

The Rh factor is a term used to describe the presence of the D antigen, the first antigen that was identified belonging to the Rh blood group system (Huang, 2013), on the surface of erythrocytes. The common potent Rh antigens reside on the RH polypeptides, whose expression is controlled by the RHD and RHCE genes, linked in tandem on chromosome one. The RHD produces the D antigen and RHCE produces the alleles Ce, ce, cE and CE compound antigens. There are about 300 allelic forms of the RHD and RHCE genes named at the molecular level. This polymorphism is due to various pattern of genomic diversification at the RH locus. The predominant mechanism of diversification at the RH locus is coding nucleotide changes and genomic rearrangement through homologous recombination.

The D antigen is clinically the most important because of its high immunogenicity and polymorphism. It has a prevalence rate of about 85% in Caucasians and about 95% in blacks (Daniels et al., 2007; Poole and Daniels, 2007). The RHD negative phenotype is characterised by high molecular diversity between serologic and molecular methods. It accounts for the incidence of alloimmunization due to pregnancy or blood transfusion, despite the numerous red cell antigens (Delaney et al., 2016; Egbor, Fellow and Knott,

2012). Most red cell alloimmunization is attributed to antigens “D” “C”, “c”, “E”, “K”, and “Jk”a (Evers et al., 2016; Flegel et al., 2016). Alloimmunization in mothers is caused by pregnancy, blood transfusion, abortion, ectopic pregnancy, amniocentesis (iatrogenic) and foeto-maternal haemorrhage (Nour, ARamy and Ali, 2011).

The absence of the D antigen designates RH negative status on human erythrocytes; its molecular basis is divided into deletion and non-deletion types. Vast majority of Caucasians with the phenotype have a total deletion of the RHD gene. The non-deletion type occurs commonly in Africans, Japanese and other Asians (Huang, 2013). There  are genomic alterations of three types that silence the D antigen expression in RH negative subjects who carry either a partial or completely intact RHD (Avent et al., 2006; Flegel, 2011). The weak D (DU) phenotype is associated with various forms of mutations that affect the quantity and quality of D antigen (Daniels, 2013; Singleton et al., 2016). Most of these mutations are novel missense mutation that results in a single amino acid substitution that resides on either transmembrane domains or cytoplasmic portion of the protein. Partial D phenotype typifies a loss and/ or an alteration of one or more of D epitopes within the context of entire D protein. They often show weakened D expression making it difficult to differentiate between partial D and weak D (Denomme et al., 2005).

Due to the density and epitope expression of the D antigen on the red cell surface, the phenotypes commonly observed are normal D positive, weak D, partial D, DEL and D negative (Ye et al., 2014). Expression of weak D and partial D is attributed to variants of antigens and a large number of alleles of RHD gene (Rizzo et al., 2012). The weak D

phenotype is due to quantitative expression of the D antigen epitopes whiles that of the partial D is due to qualitative expression of antigenic epitopes of the D antigen.

The discovery of the Rh blood group system was an insight into the instances of the haemolytic disease of the foetus and new-born (HDFN). HDFN is perpetuated by foeto- maternal rhesus antigens incompatibility (Rouillac-Le Sciellour et al., 2007). HDFN occurs as result of the immune-mediated destruction of red cells antigens of a  foetus that are not usually found on maternal red cells ( (Fasano, 2016). The common antibody produced is immunoglobulin G (IgG). The trans placental transfer of IgG antibodies attacks foetal RHD antigens leading to their destruction (Fasano, 2016). Other RH  blood group antigens that can cause alloimmunization include antigen C, E, c and e (Shao et al., 2010). Antibodies directed against epitopes of these antigens can cause alloimmunization through transfusion or pregnancy. The antibodies often encountered in Africa are anti-c, anti-C, anti-e and anti-D (Ngoma et al., 2016).

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