Age old debate on which cell type is best to use for prenatal antibody titrations.  Please chime in and feel free to add your rationale in the comments.

Now FIGHT! 

Well, the first thing to say is that red cells CANNOT be either homozygous or heterozygous (or, come to that, hemizygous).  These terms apply ONLY to genes, and red cells do not contain a nucleus.  The antigens can only be described as, at best, "homozygous", "heterozygous" or "hemizygous" expression, or, alternatively, "double" or "single dose" expression.

Then, it HAS to be accepted that, unless the maternal antibody is an autoantibody, it must be an alloantibody (or, possibly, an isoantibody), which means that to mimic the state of the foetal red cells, the red cells used to titrate the antibody MUST have a "single dose" expression.  However, that in itself presupposes that the foetal red cell antigens are all expressed at the same time, which we know is untrue (just look at the A, B and H antigens as an obvious example, but also the Kell antigens that are expressed much earlier than are the Rh antigens) or are ONLY expressed on foetal red cells, as opposed to other tissues (such as on the placental cells, which have, in some cases, been proved to adsorb the maternal antibodies).

Then, there is the fact that not all antibodies can be detected by all techniques.  This is why Reference Laboratories SHOULD have more than one technology available (and their workers should be provably competent in these techniques.  However, even then, not all techniques can predict the severity or otherwise of HDFN.  For example, antibodies within the Indian Blood Group System always show that they can cause severe HDFN by certain techniques, such as MMA, but they don't!  There is also the fact that the immunoglobulins may be IgM, IgA, IgG1, IgG2, IgG3 and IgG4 (to mention just a few), and I have yet to come across, or read about, an IgG4 immunoglobulin causing HDFN.

So, my answer is that there is a HUGE amount of knowledge known about the various antibody specificities, their titres, the expression of their cognate antigen, etc, etc, that there CANNOT be a single answer to your excellent question, but that the best thing that can be done is to read around the subject - and read around the subject from every source available - not just from a single country.

OKAY THEN, RIP ME APART!!!!!!!!!!!

Well stated @Malcolm Needs!

Semantics aside, I do see the reasoning behind either antigen configuration. Definitely different purposes though.

I did reach out to CAP to ask which they are using for their Anti-D titer PT sample.  Seems that if we are tasked with being in range with peers or their "answer key" I'd like to know what they are using as routine.  They have no documentation of what guidelines they routinely use for titer cell selection.  Hmm.. 

10 minutes ago, RRay said:

Well stated @Malcolm Needs!

Semantics aside, I do see the reasoning behind either antigen configuration. Definitely different purposes though.

I did reach out to CAP to ask which they are using for their Anti-D titer PT sample.  Seems that if we are tasked with being in range with peers or their "answer key" I'd like to know what they are using as routine.  They have no documentation of what guidelines they routinely use for titer cell selection.  Hmm.. 

The UK has (I was one of the co-authors).

Guideline for blood grouping and red cell antibody testing in pregnancy.  White, J, Qureshi, H, Massey, E, Needs, M, Byrne, G, Daniels, G, Allard S, British Committee for Standards in Haematology.  Transfusion Medicine, 2016, 26, 246–263.  doi: 10.1111/tme.12299.

29 minutes ago, Malcolm Needs said:

The UK has...

Thanks for the link!  I found the full version and it is now bookmarked.

I wish the US would come out and pick a side.  They should know us lab folk enjoy the comfort of the black and white.  Grey is for those making the rules.  Haha!

And....... of course it's a tie. 

I've been thinking about this question and I don't remember if our SOP specified what type of cell to use (I've slept a couple of times since last performing a titer).  What I do remember was that we wanted to use the same type with every repeat during the pregnancy.  In other words if the initial titer was done using an R1R1 cell for anti-D then every subsequent titer was performed with an R1R1 cell.  At the time, the change in titer was considered the most important finding.  Also, again I'm trying to awaken long dormant memories, we used a tube/saline or tube/albumin technique ( can't remember which) because that was how the original studies were done for anti-D and how the values utilized by the OB docs were derived.  I know this is ancient history for many of you but thought I would throw it out there.  

I seem to remember that titers were going out of vogue  about the time I retired and there were much more accurate methods of determining the effect on the fetus from maternal antibodies coming into use.

 

This PowerPoint Lecture gives some idea about how we approach things in the UK.  It may well be different in other countries.

In Depth Lecture on Alloimmune Haemolytic Disease of the Foetus and Newborn HDFN.pptx

How do you titer if the mom has more than one antibody?  Our policy is to titer each individually if possible.  However, I know other facilities find a cell that is positive for all of the antibodies so as to give the "overall" titer if you will.  

I prefer the each  individual one policy. Because we can not make sure the baby has the combined antigens.

Edited May 13, 20232 yr by yan xia
grammar error

I always based my judgement on the fact that the original studies to determine significant titers were done using double dose cells.  Plus, nowadays, with donor eggs, the baby can be homozygous for the antigen.