We have recently had a donor who has donated multiple times and come up positive on automated (solid Phase) antibody screen, positive in our tube antibody screen and negative in the tube antibody panel using murine monoclonal IgG. The last time the donor came in we ran the antibody panel in gel and there was a panagglutinin with autocontrol positive and Polyspecific gel DAT positive. We performed a 2x 37C allogeneic adsorbtion and ran the adsorbed plasma in gel. The adsorbed plasma again reacted same strength no change. We then made a connection that the IgG card for Ortho is Rabbit IgG, the automated IgG is Rabbit and the ABS tube method IgG is rabbit. We performed the tube antibody panel using Rabbit IgG and it too is positive now! All the same cells that were negative with the murine monoclonal IgG are now positive with the rabbit IgG. Somewhere I have read about the Rabbit IgG containing IgG4. Could this be a IgG4 warm autoantobody?

Thanks in advance!!!

It certainly could be. Monoclonal antibodies are not quite as monospecific as one might think, and, therefore, it is quite possible that one reagent may contain an anti-IgG4, whilst another may not.

IgG4 antibodies are not normally clinically significant. Although this patient may have a positive DAT and a panagglutinin in the plasma, is the donor noticably anaemic? If not, this may also point to an IgG4 auto-antibody (although, of course, as his/her antibody may be polyclonal, there may also be elements of IgG1, IgG2 and/or IgG3 present, so this is not a "clincher").

Check the package insert for the monoclonal Anti-IgG. It may give you an indication if that particular reagent does not detect IgG4 antibodies. We have seen this before for some alloantibodies such as Anti-Yta which can be IgG4.

Check also to see if the anti-IgG that was giving you a positive in the beginning is truly an IgG or if it can also react with IgA/IgM. It should specify in the box insert. That could also explain the discrepancy

Edited December 4, 201212 yr by galvania
spelling error

We have seen the monoclonal Anti-IgG miss an anti-JMH which reacted strongly with Rabbit anti-IgG. JMH's are generally IgG4, so it makes sense. I doubt this is the case in your patient though, since we normally see anti-JMH in older patients. But I would agree, it is probably due to some kind of IgG4 antibody.