Are DQA Antibodies Real?

J. Jones, D. Lucas, M. Leffell, A. Zachary.

Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Meeting: 2015 American Transplant Congress

Abstract number: B245

Keywords: Epitopes, HLA antibodies, Sensitization

Antibodies specific for HLA-DQ antigens appear to be increasing in frequency in the post-transplant period and are difficult to reduce effectively with desensitization protocols using plasmapheresis and IVIg. Detection of these antibodies has been greatly facilitated by the development of multiplex bead technology. DQ antibody may be specific for epitopes on the alpha chain or beta chain, or for an epitope that results from the quaternary structure of the two chains combined. We have examined 27 patients with apparent DQA antibody. We determine the specificity to be DQA when positive reactions occur with various DQB antigens bearing the same DQA and when negative reactions occur molecules having the same DQB but a different DQA. In some cases, the specificity can be further validated because the patient's phenotype contains a DQB for which there was a positive reaction. Among our 27 patients, DQA5 was the predominant specificity, occurring in nearly 52% of patients. However, this is most likely due the the frequencies of DQA1 and DQA3 antigens in 70% and 33% of patients, respectively, and only 11% with DQA5 antigen in their phenotypes. There were three patients for which there were crossmatch data two of which had serum adsorptions performed with cells bearing the relevant DQA antigen. These data are shown here.

Table 1

PATIENT	SPECIFICITY	XM – unadsorbed serum	MFI – unadsorbed serum	MFI – adsorbed serum
RC	DQA5	CDC>256	20,844	20,671
AP	DQA5	NEG CDC	19,885	ND
JC	DQA2	FCXM NEG	10,325	5, 706

The target cell in the RC XM was mismatched only for DQA5. The failure to reduce the MFI values with adsorption is most likely due to bead saturation. However, we would have predicted a positive XM with the AP serum since there were antibodies to DR as well as DQ. Also, sera with MFIs in the range of 10,000 are usually rendered negative by adsorption, unlike the partial reduction in MFI seen with the JC serum. DQ molecules, with two polymorphic chains may be less stable than A, B or DR molecules. These data suggest the presence of antibodies to non-native epitopes which, in turn, has important clinical implications.

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