Antibodies and homozygous cells

[klsmith]

I am wondering, can an antibody to a major blood group be present but not react with all homozygous cells on the panel?

[Mabel Adams]

I have seen this fairly often with Kidd antibodies in gel. The antibodies are usually weak.

[Malcolm Needs ☆]

I am wondering, can an antibody to a major blood group be present but not react with all homozygous cells on the panel?

Well, yes and no (not a helpful answer, I know)!

The thing is that, unless the genotype of the donor has been performed, what appears to be a homozygous expression of a particular antigen may not be. Take, for example, a panel cell that is Fy(a-b+). This suggests that the genotype of the donor is FYB/FYB, but, in reality, it could be that the donor is FYB/FY, and so the Fy( antigen is present "in a single dose". The same can apply to every other phenotype, where the donor appears to be homozygous for the gene governing a particular blood group antigen. They may actually be expressing the antigen as a "single dose".

[John C. Staley]

Well, yes and no (not a helpful answer, I know)!

The thing is that, unless the genotype of the donor has been performed, what appears to be a homozygous expression of a particular antigen may not be. Take, for example, a panel cell that is Fy(a-b+). This suggests that the genotype of the donor is FYB/FYB, but, in reality, it could be that the donor is FYB/FY, and so the Fy( antigen is present "in a single dose". The same can apply to every other phenotype, where the donor appears to be homozygous for the gene governing a particular blood group antigen. They may actually be expressing the antigen as a "single dose".

Malcolm, how common is this? As much as I hate to admit it, this is the first time I have heard of this possibility. I think you've just give a lot of people something else to keep them awake at night!

[Malcolm Needs ☆]

Malcolm, how common is this? As much as I hate to admit it, this is the first time I have heard of this possibility. I think you've just give a lot of people something else to keep them awake at night!

Well, the problem is John that we don't actually know, because nobody has done any work on it in terms of population statistics since molecular techniques were invented, but, that having been said, it is not common except in certain ethnicities for certain genes.

For example, the FY gene is relatively frequent within the Black population. Although the Fy(a-b-) phenotype has a frequency of about 68% in the Black population, nobody really knows how many of these are actually FYB/FYB, with the homozygous FY GATA1 mutation (except, it is know that it is most), how many are FYB/FY, homozygous for the FY GATA1 mutation, how many are FY/FY, homozygous or heterozygous for the FY GATA1 mutation, and how many are genuinely FY/FY, without the FY GATA1 mutation (except that it is probably the minority).

The silent JK gene is more frequent in a donor who originates from the Far East........and so on and so forth.

It is rare for a donor whose red cells are used in a panel to show dosage when their phenotype appears to express "homozygosity", but it does happen.

Obviously, some donors, apparently R1R1 are actually R1r', and some donors, apparently R2R2 are actually R2r".

[jill]

If the antibody is newly formed this can occur due to a "poor fit" that the new antibody has. As time goes on the antibody's FAB portion changes to fit its epitope better as the B cells become more mature in recognizing the red cell antigen.

[Dr. Pepper]

Once in a while I have seen weak antibodies teetering on the edge of undetectability (anti-c comes to mind) that may not react initially with all homozygous antigen-positive cells, but do so if you move to a technique that may be more sensitive for the given antibody (LISS to enzyme or PEG, longer incubation etc.). I wonder if this may be technique-driven (one extra shake with that tube). And as Malcolm elegantly points out, we may make mistaken assumptions about zygosity looking at the panel scoresheets.

The reagent company may make an error. A month ago, I was preparing a practical for my med tech students and wanted to see how a patient anti-Fyb was reacting in the antibody screen. It was 2+ with a homozygous (we assume!) cell but I saw no reaction with a heterozygous cell. I was puzzled as it had reacted 1-2+ or so with screening and panel cells before I froze it up a week before. The screening cells were outdated (they were actually replaced the day before we tested the patient in question) but still, I thought the cell should have reacted. So I tried the company's reagent anti-Fyb and that didn't react either. The antisera reacted 2+ with several other heterozygous cells. So I don't think the cell was Fyb+ (or maybe was a Fyx?). I called them to give them a FYI but they said they don't really investigate complaints regarding outdated reagents. All in all, it was an unsatisfactory experience. I'd be curious if anyone else has had similar experiences.

[Auntie-D]

Well, the problem is John that we don't actually know, because nobody has done any work on it in terms of population statistics since molecular techniques were invented, but, that having been said, it is not common except in certain ethnicities for certain genes.

Masters project anyone?

[Malcolm Needs ☆]

Masters project anyone?

I'd want a PhD (minimum) for that!!!!!!!!!!!!!!!!!!!!!!!!!!!!