Background
Human IgG exists in 4 different subtypes (IgG1, IgG2, IgG3, and IgG4), but it is also now appreciated that there is genetic variation within IgG subtypes (called isoallotypes). 29 different isoallotypes have been described, with 7, 4, 15, and 3 isoallotypes described for IgG1-IgG4, respectively. The reactivity of anti-IgG with different isoallotypes has not been characterized.
Study Design and Methods
A novel monoclonal anti-K antibody (PUMA1) was isolated, sequenced, and a panel of PUMA1 variants was expressed consisting of the 29 known IgG isoallotypes. The resulting panel of antibodies was pre-incubated with K+ RBCs and was then subjected to testing with currently approved anti-IgG, by flow cytometry, solid phase systems, gel card, and tube testing.
Results/Findings
An FDA approved monoclonal anti-IgG (Gamma-clone) failed to recognize 2 out of 15 IgG3 isoallotypes (IgG3-03 and IgG3-13) and 3 out of 3 IgG4 isoallotypes (IgG4-01, 02, 03). In contrast, an FDA approved rabbit polyclonal anti-IgG recognized each of the known human IgG isoallotypes.
Conclusion
These findings demonstrate “blind spots” in isoalloantibody detection by a monoclonal anti-IgG. Should a patient have anti-RBC antibodies predominantly of an IgG3 subtype of the IgG3-03 and/or IgG3-13 variety, it is possible that a clinically significant alloantibody would be missed. IgG-03 and IgG-13 are estimated at a frequency of 1–3% of Caucasian and 20–30% of certain African populations. The non-reactivity with IgG4 is a known characteristic of this monoclonal anti-IgG, but IgG4 isoallotypes have not been previously reported.