Anti-C titer 0 (Zero)?

[Curious]

I am curious. A patient had Antibody screen which came back positive for Anti-C, but when it was sent for titer, the titer came back as 0 (zero). Is this considered a false positive? or an extremely low titer? What does this mean for someone who is attempting to be a gestational surrogate?

[JOANBALONE]

It could be a low titer anti C reacting only with double dose C positive cells. The cell used to titer the antibody was probably single dose (heterzygous) C positive.

[Malcolm Needs ☆]

I am curious. A patient had Antibody screen which came back positive for Anti-C, but when it was sent for titer, the titer came back as 0 (zero). Is this considered a false positive? or an extremely low titer? What does this mean for someone who is attempting to be a gestational surrogate?

I'm not sure if you are a Blood Banker who is attempting to be a gestational surrogate, or a "lay member" of the public who is attmpting to be a gestational surrogate, and so I am going to attempt to answer your question as if you are the latter. Apologies if you are the former, and I am assuming too little knowledge.

Anti-C is an antibody that can be made in the plasma (the liquid part of the blood) against the C antigen, part of the Rh Blood Group System, on red cells. Normally, an individual will only make anti-C if they lack the C antigen themselves (very rarely, it can be formed as an auto-antibody) and have been exposed to the C antigen, either by transfusion or pregnancy. Again, very rarely, it can be made for no apparent reason (a so-called "naturally-occurring" antibody).

Both the antibody and the antigen are proteins (in a way).

As such, they are direct gene products. You have 43 pairs of chromosomes, plus, in your case, 2 X chromosomes. The part of the chromosome that encodes for the C antigen is found on chromosome 1. However, as you have pairs of chromosomes, you have 2 copies of chromosomes (one from Dad, one from Mum).

The C gene has a "opposite" known as c.

Therefore, you can have two copies ofthe C gene, one copy each of the C and c gene, or two copies of the c gene (which, I presume you have, as you have produced anti-C).

Sometimes, an antibody will only react with red cells that exhibit the "double dose" of the antigen (in this case, this would mean that the red cells are from someone who has inherited the C gene from both parents - in effect, they have a "double dose" of the C antigen, as there is no c antigen present - there are a finite number of C and/or c antigen sites per red cell - and so someone who has inherited a C and a c gene will have half of these sites as C, and half as c).

When we are screening for antibodies, and when we are identifying the specificity of an antibody, we tend to use cells that are "CC" and others that are "cc", so that we can detect really low levels of antibody.

On the other hand, when we are performing a titration of the antibody, we use "Cc" red cells, as the baby will either be "Cc" or "cc" (depending upon what the baby inherits from the Dad), but the baby cannot be "CC", as the Mum has no C gene to donate to the baby.

Therefore, there will be occasions where an anti-C can be identified in the plasma (using "CC" red cells), but, because it is so weak, cannot be detected in the titration using "Cc" red cells - hence the titre is 0!

Anti-C has only very rarely every been implicated in haemolytic disease of the newborn, and even then when the titre is very high, so I wouldn't worry too much about it if I were you.

I hope that this rather lengthy explanation helps, but if it doesn't, please feel free to say so, and I'm sure someone else will be able to put it better.

:D:D:D:D

[Curious]

the result reads:

"The ABO group and RH typing were not performed. Her antibody screen is reactive in 1 of 3 cells using gel technology. The autocontrol is negative.

In an attempt to clarify the antibody specificity, the plasma from the patient was reacted with a commercially available antigen typed cell panel (Ortho-Clinical Diagnostics lot # VRA147) containing 11 cells using gel technology. 4 of 11 cells reacted with specificity for Anti-C. All other common clinically significant alloantibodies were excluded.

Serologic Titration study: Titer = 0 (C titer)

Diagnosis: Clinically significant alloantibody identified: Anti-C"

Does this mean it is a very low titer?

[Deny Morlino]

Kudos Malcolm! A nice explaination I think.

[Curious]

Thank you Malcolm Needs......you are AWESOME!!!!

[Deny Morlino]

Thank you Malcolm Needs......you are AWESOME!!!!

Another member of the Malcolm Needs fan club is created, lol!

Malcolm is indeed an awesome educator with the gift of breaking things down so most others can understand.

[Malcolm Needs ☆]

Thank you both.

I feel quite humble.

In answer to your "green" question, Yes, it means that the titre is very, very low.

:D:D:D:D

[David Saikin]

If the ab id is in gel and the titer is done in tubes, the answer may very well be "0" because of the sensitivity/lack of between gel and tubes. A 2+ or weaker reaction in gel will be undisoverable using tubes.

[dcubed]

When we have an anti C to do titration studies on we use R1R1 cells per the procedure listed in "Judd's Methods in Immunohematology" third edition. Why?

[L106]

I suspect the David is correct (that the titration was performed using a different testing technique or methodology than what was used for the Antibody Identification.)

Yes, the Anti-C titer is very low.

[Malcolm Needs ☆]

When we have an anti C to do titration studies on we use R1R1 cells per the procedure listed in "Judd's Methods in Immunohematology" third edition. Why?

Goodness only knows, because the baby MUST either be cc or Cc. The baby CANNOT be CC. Therefore, using R1R1 red cells cannot mirror the in vivo situation - and, as far as I know, using a "heterozygous" red cell for titration is almost universal throughout the world (except where such cells are unavailable, such as Vel)......and I know red cells can't be heterozygous; only genes!

:crazy::crazy:

[RR1]

Goodness only knows, because the baby MUST either be cc or Cc. The baby CANNOT be CC. Therefore, using R1R1 red cells cannot mirror the in vivo situation

y:

Would it not be a good idea to mimic "worst case scenario"-especially in the case of a surrogate pregnancy, where the foetus may well be R1R1?

[Malcolm Needs ☆]

Well, I suppose so in that situation, but, a) this would be incredibly rare and in such a situation I would recommend foetal genotyping anyway, to see if the foetus is RHCRHC or RHCRHc (or even RHcRHc), and even then, only if the antibody was showing dosage.

The other thing is, of course, that in the UK, all the work has been done using cells with heterozygous expression of the antigen (with a titre of 32 or above making us start to fret). We would have to validate a method using cells with an apparent homozygous expression of the antigen, so that we would know at what titre we should start to worry. In such a scenario, it may just be better to monitor the pregnancy closely by MCA Doppler/ultrasound (but I wouldn't worry too much about an anti-C in any case, which has never been reported to cause anything but mild HDN).

Edited November 6, 2010 by Malcolm Needs