The Pathogenesis of ABO Haemolytic Disease of the Newborn

Abstract

A study of the pathogenesis of ABO HD is essentially a study of the interrelationships of the maternal IgG anti-A/anti-B antibodies with the various components of the 'protective mechanism'.There is an equilibrium of IgG antibodies across the placenta and thus, ABO HD occurs more frequently in cases with high titre IgG antibodies than in cases with low titre IgG antibodies.The foetal blood group substance 'protects' the infants by competing with the red cells for the incompatible antibodies. Small amounts of the homologous blood group substance reduce the IgG anti-A/anti-B reaction with A/B red cells and the degree of inhibition increases as the antigenic strength of the red cells decreases.Possible reasons for the difference in combining power of the various adult and foetal red cells are discussed.A small deficiency of non-secretor infants and fathers was observed and the possible roles of secretor status in ABO HD are discussed.The incidence of A130 haemolytic disease (ABO HD) is far lower than the incidence of ABO incompatible pregnancies and it was realised t h a t this must result from the action of a protective mechanism. This was believed t o consist of, soluble A or B blood group substances in the foetus [l, 39,401, weak foetal antigens [22,40], and the restriction by the placental barrier on the passage of antibody from mother t o foetus. (Only 'complete' antibodies known at that time.) The protective mechanism was studied by TOVEY [40] and his paper should be consulted for a review of the early work.Soon after the demonstration of incomplete antibodies, WIENER and SONN [45] showed that the placenta was permeable t o the incomplete antibodies. I n a later paper WIENER and UNGER [47] demonstrated that the babies of group 0 mothers are apt to acquire about sixteen times as much antibody as babies with mothers of

An Explanation of the Failure of the Direct Antiglobulin Test to Detect Erythrocyte Sensitization in ABO Haemolytic Disease of the Newborn and Observations on Pinocytosis of IgG Anti‐A Antibodies by Infant (Cord) Red Cells

“…The substantially lower levels reported here reflect the sub-maximal levels of antibody used. This level was shown by the titration studies (Table IV) to be similar to that in many cases of ABO haemolytic disease (Voak, 1969). It should also be noted that only about 40% of the antibody is ferritin-conjugated and that which is conjugated has to compete for sites with unconjugated IgG antibodies.…”

“…However, less antibody was eluted from the strongcr A infant cells than from either the weaker A infant or adult A, cells and therefore these results did not suggest that the greater absorption of antibody by the stronger A, infant cells was due to pinocytosis. The amounts of antibody eluted from the cells of the A, infant blood samples were similar to those found in eluates from the cells of many ABO HD cases studied by Voak (1969). The A status of the adult and infant blood samples studied was as shown in Table IV.…”

“…However, the studies with IgG anti-A/B antibodies presented elsewhere (Voak, 1969) do not support the views of Haberman and his colleagues since infant A/B cells are shown to give strong antiglobulin test reactions when they are heavily sensitized. In addition, Hostrup (1963) and Voak (1969) have shown that the A/B substances in the group A/B infants' sera inhibit the antiglobulin reaction with IgG anti-A/B antibodies, and that the degree of inhibition increases as the antigenic strength of the red cells decreases. Thus, in cases of ABO heterospecific pregnancy, the A/B substances in the infants' sera compete with the weaklyreacting foetal cells for the incompatible antibodies.…”

“…Conjugation offerritin to the IgG anti-A/B* globulin resulted in an 'electron dense' reagent that retained the serological specificity and activity of the unconjugated reagent as shown by the results in Table I the red cells from the Al and A, adult and infant blood samples (Table 11) revealed that infant cells may give strong antiglobulin test reactions when they are heavily sensitized (Voak, 1969 The results of the titration studies on the conjugated sera, after absorption by equal volumes of cells from the Al and A, adult and infant blood samples, and in the eluates prepared from the sensitized cells (as used in the electron microscopy) are shown in the Tables I11 and IV respectively. These results demonstrate that the cells of both adult and infant group A blood samples exhibit the reaction with anti-A antibodies as first noted by Fischer & Hahn (193g), i.e.…”

Untersuchungen zur Diagnostik der ABO-Erythroblastose mit der Elution nach Lui-Eicher

“…nicht gefunden werden (2)(3)(4)(5)(6)(7)(8). In der vorliegenden Arbeit wird über Ergebnisse von Untersuchungen an Nabelschnurerythrozyten von Müttern der Blutgruppe 0 berichtet, sowie über Ergebnisse von Untersuchungen, die zum Verständnis der oben beschriebenen Befunde beitragen sollen.…”