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C3d Positive DAT in cord blood.


Malcolm Needs

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All of the gel cards we use are IgG/C3d, mainly because they are the same cost the same as soley IgG ones and we do that few that they would expire - so we use them for everything. We do seem to pick up a few antibodies that our reference lab who use IgG only Ortho cards don't seem to find. If the antibodies are C3d reacting that would explain it... It has been a bug-bear of mine for a while - they describe us as 'oversensitive'.

Does anyone know if anti-c is more reactive with C3d? We have a patient who has Anti-c but the titres are too low for our reference lab to pick up - we get 3+ though...

In our reference lab we sometimes see antibodies that are to weak for titration while the hospital finds them strong reactive. One reason can be that beside the anti c there is also an anti f or anti cE present (you will not found) and reactions with different phenotypes can be different in strength. The other option is that for pregnancy the titrion is determined in a tube methode with no additives, while most hospitals will use a tube with PEG or a column method (which is much more sensitive).

Peter

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Back to the original case.

Malcolm, Maybe it is nice to test the complement level of the child (CH50 titration), and maybe compare it to other newborn. When you want to write a paper this test can be of help.

As far as I know the amount of complent proteins is low at end before birth, and therefore anti Jk antibodies (mostly) do not much harm.

Peter

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Nice suggestion Peter, but these cases are so few and far between (I've only ever seen about seven or eight - maybe because they are not always sent into our reference Laboratory) that it would be extremely difficult to do - but I will CERTAINLY keep it in mind.

Thanks.

The other newborn sera I mentioned was from childeren that were not affected by anti Jk or form normal newborns

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Yes, I see from where you are coming Peter, and we can certainly do that, but it is the "positives" (i.e. the ones that come up with anti-C3d) that are so rare, and not all cord samples born to mothers with anti-Jka are sent in to us at the reference Centre.

I suppose that I could ask for them to be sent in?

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Malcolm, forgive me if I am mistaken here but somewhere along my BB practice I aquired the understanding that the Corb blood is some mixture of fetal and maternal blood (usually much more fetal cells than maternal cells with the exception of the unusual) and if you are seeing this unexpected level of reactivity with the C3 component of the DAT then have you considered testing the fetal and maternal cells individually to be sure that the reactivity seen is do to complement fixation of the fetal cells alone? And if you are already well on top of this (which you probably are) any explaination would be greatly appreciated.:)

Edited by rravkin@aol.com
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Well, we didn't do a Kleihauer, but we did test the sample with IgM anti-Jka and anti-Jkb, and there was no mixed-field with the anti-Jkb, which you would expect if that were the case.

The other thing is though, why, oh why, do we only ever see this with maternal Kidd antibodies, if it were a mixture of fetal and maternal blood, even when there are antibodies of a different specificity present in the maternal blood, with no Kidd antibodies, but which are known to activate complement?

Like Peter suggests, I need to do some more (scientific) work on this, but the fact that it is always Kidd antibodies suggests to me that there must be some kind of connection.

It's bugging me to be honest!

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We quantify the anti-c or the anti-D in ALL cases in pregnancy, unless the anti-c or anti-D can only be detected with enzyme-treated red cells (i.e. not by IAT), or unless the anti-D is proven to be low in terms of IU/mL (<1.0 IU/mL) following prophylaxis.

The quantification is performed once every 4 weeks until 28 weeks gestation, and then every 2 weeks until delivery, unless the level is rising enough to worry us about the chances of HDFN, in which case we will perform it more often (or there is a sudden, big rise).

We also do it every 2 weeks following an IUT (but this testing of the maternal plasma is more to ensure that she has not produced any other atypical alloantibodies, rather than to see the level of anti-c or anti-D, because, of course, by this time she will be under the care of a Specialist Foetal Medicine Unit, who will be monitoring the foetus by other means).

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Hi Malcolm. I'm musing aloud again - I don't think that this is anything to do with a mixture of fetal and maternal cells. I'm sure there are only fetal cells present. The big question is where does the complement come from. If it is fetal complement, then why don't you see complement on fetal cells when the mother has other complement activating antibodies, in particular anti-A. And all the literature seems to indicate that fetal complement is not very efficient, which I think is actually pretty logical.If it is maternal complement crossing the placenta, why would it only do so if the mother makes an anti-Kidd? But we all know that Kidd antibodies are wierd anyway. What about this as a possibility - that the presence of Kidd antibodies actually stimulates complement production in the liver. I don't mean that they just activate complement in the normal sense, but that they actually stimulate its excessive production. I have no evidence whatsoever for this. It's just an idea that we can play ping pong with.

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And me again. Just been refreshing my tired brain cells with the wisdom of Geoff Daniels on Kidd antibodies. I quote - 'Around 40-50% of sera containing Kidd antibodies bind complement........only those Kidd sera with an IgM component are capable of complement binding as IgG Kidd antibodies are unable to fix complement'. I had forgotten that rather major point - which just makes things worse, of course...........

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What about this as a possibility - that the presence of Kidd antibodies actually stimulates complement production in the liver. I don't mean that they just activate complement in the normal sense, but that they actually stimulate its excessive production. I have no evidence whatsoever for this. It's just an idea that we can play ping pong with.

I agree that Kidd antibodies are pretty wierd.

I am prepared for any reasons, but I'm not sure about this one (but that doesn't mean I am ruling it out, out of hand)!

The baby, as far as we know, is perfectly okay.

Edited by Malcolm Needs
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And me again. Just been refreshing my tired brain cells with the wisdom of Geoff Daniels on Kidd antibodies. I quote - 'Around 40-50% of sera containing Kidd antibodies bind complement........only those Kidd sera with an IgM component are capable of complement binding as IgG Kidd antibodies are unable to fix complement'. I had forgotten that rather major point - which just makes things worse, of course...........

I'll ask Geoff about that, because the anti-Jka MUST be IgG, otherwise it wouldn't have gone through the placenta.

We got around the Wharton's jelly possibility by washing the red cells Auntie-D.

I've sent Geoff the photograph and a quick explanation of what it is, but his out of the country until 26th November.

Edited by Malcolm Needs
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  • 4 weeks later...
I'll ask Geoff about that, because the anti-Jka MUST be IgG, otherwise it wouldn't have gone through the placenta.

We got around the Wharton's jelly possibility by washing the red cells Auntie-D.

I've sent Geoff the photograph and a quick explanation of what it is, but his out of the country until 26th November.[/quote

A most interesting thread, everyone. I might be a tad out of date, but It seems to me that "complement can't cross the placenta" was the mantra. So are we thinking that the baby is producing the complement? And then the allegory to the mantra was (or at least used to be) "there has never been a documented case of complement-induced HD(F)N" - is this out of date as well?

Also, in response to another query in this thread (sorry, I'm not sophisitcated enough to quote two posts - I'll frankly be impressed with myself if the first quote comes up! :rolleyes: ):

Our lab tests infant DATs by gel card, either by polyspecific (just to use the inventory of polyspecific cards) or by IgG card. A positive by either of those cards is as far as we take it; we do not go on to characterize it as to IgG, C3, or polyspecific. We simply report out "weakly positive" )1 tp 2+) or "strongly positive" (3 to 4+).

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To be honest bb4me, I'm not sure from where the complement came (mum or baby), but, in view of the fact that I have never seen this phenomenon with any antibodies other than those within the Kidd Blood Group System, whilst I have seen many examples of positive DAT's on cords wherre the maternal antibody is of another specificity that is known to "fix" complement, I still wonder if it something to do with the Kidd BGS antibodies. I just don't know!

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Hi Malcolm,

I'm going to stick my head above the parapet & come from an alternative angle or 2...

This paper http://journals.lww.com/pedresearch/Fulltext/1997/03000/Alternative_Pathway_Activation_of_the_Complement.5.aspx

discusses complement protein levels in preterm & full-term babies. They argue that despite full-term babies having C1, C2,C4, C3 levels at 50% of maternal levels, their mechanisms for complement activation appear to be intact.

So is it possible this is the baby's true response to the anti-Jka afterall?

Or, as the antibody appears so weak, might the baby have an infection that is confusing the serological picture??

What do you think? *withdraws head to avoid shooting!*

Thank you for posting such an interesting case!

Robina

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Hi Robina,

Long time, no hear!

I think it more likely that it is the baby's own complement. Don't forget that, although the antibody may be weak, it only takes two IgG molecules to be close together to start off the complement cascade, which causes amplification, and it is thought that the Kidd antigens are clustered, so this would be quite within reason.

There is no evidence that the baby had any "nasties" on board, so I think that we can forget the infection idea (but not dismiss it as a cause in another case).

No shooting today - I'm in a mellow mood (well, hung-over actually)!!!!!!!!!!

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On a practical level, though, Malcolm, am I right in thinking that the baby was not actually suffering from HDN so that even though the baby had a positive DAT due to C3d and you could elute anti-Jka off the red cells, it is a bit academic. In other words, anyone only doing IgG DATs on newborns does not have to worry that they might be missing a life-threatening anti-Jka; and that a woman with anti-Jka does not have to fear for her unborn baby?

Happy birthday, by the way; but you DO know that you're not allowed to retire from Blood Bank Talk even when you retire from paid work, don't you :o

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