My Opinion: Use Gamma-Heavy-Chain-Specific AHG Reagent

There are many types of antiglobulin reagent available which have differing specificities to immunoglobulins (e.g. whole molecule IgG, IgG-heavy-chain specific, IgM-heavy-chain-specific, IgA-heavy-chain-specific) and complement fragments (e.g. C3b, C3c, C3d).

For the purpose of antibody identification using the indirect antiglobulin test IAT, normally polyspecific, whole molecule IgG, and/or gamma-heavy-chain-specific reagents are used.

The purpose of antibody identification is normally to detect clinically significant antibodies—NOT ALL ANTIBODIES.  In a busy hospital blood bank, I am not routinely interested in detecting cold antibodies that do not react at 37C.

Polyspecific reagents will detect both complement and/or immunoglobulin and are commonly chosen.  However, the complement may detect insignificant cold antibodies that may obscure clinically significant IgG antibodies.

A whole-molecule IgG reagent is not really monospecific since it detects both heavy and light chains.  The light chains (kappa and lambda) are shared by all classes of immunoglobulin.  Thus, an IgM antibody (usually cold) may show weak reactivity—nonspecific cold antibodies may be detected!

My usual choice is to routinely use a gamma-heavy-chain-specific reagent.  I have been using this for many years and it expedites the workflow.  The likelihood of missing a clinically significant antibody is rare.  In my long career, I have only detected a small number of Kidd antibodies that required a polyspecific reagent with complement. 

If there is a nonspecific antibody, I will check the Jka and Jkb typings.  If either is negative, I will check for an antibody showing dosage and consider using a polyspecific reagent.  I have previously reported such an antibody in an earlier post—it is extremely rare!

Another consideration is the detection of interference from a new chemotherapy reagent, anti-CD47.  This nonspecific reactivity will be eliminated by using a gamma-heavy-chain specific reagent:

This is an example of a nonspecific reagent using whole molecule IgG AHG:

Here is the same sample using gamma-heavy-chain-specific AHG: