Hello all,

Any truth to the maxim which I've inherited in my training which is that anti-Jka can do funny things on the panel?  e.g. react with heterozygous donors and then not react with homozygous donors?  React inconsistently?

Not sure if this lore can be confirmed by others ...

Thanks!

Yes. And worse, some cells react differently, including having no reactivity,  as compared with cells of the same degree of zygosity.  Thus the possibility of Kidd antibodies needs to be seriously considered when the recipient is negative for one or both antigens and the panel is reactive but without clearcut specificity for Jka or Jkb.

Edited July 23, 20241 yr by Neil Blumberg

I worked in Red Cell Immunohaematology for most of my 43 years before retirement, including two times at the International Blood Group Reference Laboratory (IBGRL), and for over a decade at one of the NHS Blood and Transplant Centres in London.  During that time, I saw some pretty weird Kidd antibodies, but never came across an example of one that reacted with red cells with Jk(a) heterozygous expression, but not with Jk(a) homozygous expression.

One such "weird" type (although I never saw one) was the extremely rare, dominant inhibitor type In(Jk), similar, but, of course, not identical to In(Lu).  These red cells usually type as Jk(a-b-), but their true Kidd type can be ascertained by Adsorption and elution tests..  These red cells are also more resistant to haemolysis by 2M Urea than red cells with "normal" expression of the Kidd antigens, but less resistant to haemolysis by 2M Urea than true "amorphic" Jk(a-b-) red cells.

There are approximately 14, 000 copies of the Kidd carrier molecule per red cell (quite a small number, when compared with some other carrier molecules, such as the D antigen).

The amino acid residue that defines either the Jk^a or Jk^b antigens is very close to the red cell membrane in the 4^th extracellular loop but is largely “hidden” by the 3^rd extracellular loop (steric hindrance).

 Both facts may contribute to the weak reactions between Kidd antibodies and Kidd antigens.

Schematic of the Kidd carrier molecule (after Wester ES, Storry JR, Olsson ML.  Characterization of Jk(a+weak): a new blood group phenotype associated with an altered JK*01 allele.  Transfusion 2011; 15: 380-392.  DOI: 10.1111/j.1537-2995.2010.02795.x.

In this paper, Wester et al also describe weakened forms of both the Jk^a and the Jk^b antigens, but in each case, the amino acid substitution is remote from position 280 of the mature protein. 

 In addition, an individual with the Trp171Arg mutation with weak Jk(a) expression has produced an anti-Jk3 or anti-Jk3-like antibody, and so they may be “dangerous patients” (Whorley T, Vage S, Kosanka J, Lose SR, Sandquist AR, Copeland TR, Westhoff CM.  JK alleles associated with altered Kidd antigen expression.  Transfusion 2009; 41 (Suppl.): 48A-49A (abstract).

Lastly (for now anyway!), most foetal red cells sensitised by maternal antibodies react only with anti-IgG, but I (and a colleague Grant Webb) have both noticed, but not published, occasions when such red cells also react with anti-C3d and, in one case, only anti-C3d (see genuine photographs below)..

I should have also said that there is an excellent Blood Group Review available, viz Hamilton JR.  An update to Kidd blood group system.  Immunohematology 2024; 40: 28-33.  DOI:  10.2478/immunohematology-2024-005.

I've seen it at least 2, maybe 3 times where reactions were consistent (ie repeatable) but didn't behave as expected - first of all, generally weak reactions, nothing stronger than a strong 1+ in gel, but reacted with some (not all) homozygous Jk^a cells and some (not all) cells that were heterozygous. each time, we threw more cells at it to prove/disprove the anti-Jk^a conclusion and each time the only consistency was that all of the reactive cells had the Jk^a antigen. could it have been some other antibody for which our panel cells didn't note the corresponding antigen? sure. but i wouldn't ignore the consistent presence of the Jk^a antigen on the reactive cells...

Thank you all for your thoughtful responses.  Much appreciated!