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Impact of IgM and IgG3 Anti-HLA Alloantibodies in Primary Renal Allograft Recipients

Everly, Matthew J.1,7; Rebellato, Lorita M.2; Haisch, Carl E.3; Briley, Kimberly P.2; Bolin, Paul4; Kendrick, William T.5; Kendrick, Scott A.5; Morgan, Claire4; Maldonado, Angela Q.6; Harland, Robert C.3,4; Terasaki, Paul I.1

doi: 10.1097/01.TP.0000441362.11232.48
Rapid Communication

Background: With standard IgG donor-specific anti-HLA antibody (DSA) testing, it is unclear which immunoglobulin-G (IgG) DSA positive patients will fail. We looked further into the immune response by studying immunoglobulin-M (IgM) and IgG subclass 3 (IgG3) DSA to determine if these identify the IgG DSA patients at highest risk for allograft loss.

Methods: In 189 consecutively transplanted primary renal allograft recipients, sera were collected sequentially pre- and posttransplant. Of the 189, 179 patients had sera available to retrospectively test for anti-HLA IgG, IgM, and IgG3 antibodies via LABScreen single-antigen bead assay and were included in the study. All patients had a negative crossmatch. Per patient, all DSA (IgM, IgG3, and IgG) refers to the same serologic specificity.

Results: Overall, 100 (56%) patients developed an alloimmune response (IgM or IgG DSA positive, or both). Ninety-five patients developed IgM DSA and 47 patients developed IgG DSA. IgM DSA was detected in 42 of 47 patients with IgG DSA. IgM DSA alone did not increase the allograft loss risk, whereas IgG DSA did (P=0.002). Once IgG DSA appeared, IgM DSA persisted in 33 patients and an isotype switch to IgG3 positive DSA occurred in 25 patients. Patients with IgM persistent IgG3 positive DSA (n=19) were more likely to have allograft failure than those without (P=0.02).

Conclusion: This study shows the evolution of the humoral immune response from IgM to IgG DSA posttransplant. We found that development of IgM persistent IgG3 positive DSA identifies the most dangerous IgG DSA subpopulation.

1 Terasaki Foundation Laboratory, Los Angeles, CA.

2 Department of Pathology, Brody School of Medicine at East Carolina University, Greenville, NC.

3 Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC.

4 Department of Medicine, Brody School of Medicine at East Carolina University, Greenville, NC.

5 Eastern Nephrology Associates, Greenville, NC.

6 Vidant Medical Center, Greenville, NC.

7 Address correspondence to: Matthew J. Everly, M.D., Terasaki Foundation, 11570 W. Olympic Blvd., Los Angeles, CA 90064.

This article was funded in part by the Paul I. Terasaki Foundation.

P.B. has received funding for research from Novartis and Astellas. P.B. is also on the speaker’s bureau for Novartis. The other authors have no conflicts to disclose.

E-mail: meverly@terasakilab.org

P.B., C.H., W.K., S.K., and R.H. treated the patients; L.R., M.E., P.T., and K.B. collected the data and conducted the HLA typing and antibody testing; M.E. analyzed the data; and M.E, A.M., and L.R. wrote the article.

Received 23 September 2013. Revision requested 17 October 2013.

Accepted 4 December 2013.

Accepted January 31, 2014

© 2014 by Lippincott Williams & Wilkins