Numerous publications have shown secondary antibody testing of IgG (subclasses, C1q, etc) in de novo DSA (dnDSA) positive patients may have clinical relevance. Herein, we performed longitudinal testing of a multitude of secondary tests (IgG3, IgG4, C1q, IgG dilutions, IgM) in 41 consecutive dnDSA positive patients to see which of these test discern clinical risk and when is the most valuable time to test with these.

Methods: All patients received their first transplant between '06 to '10, had 3 years of post-dnDSA follow-up, and were pre-txp IgG DSA(-). All patients were tested at the following time points: at the time of DSA onset, at 6 months post dnDSA, and once between 12-24 months post-dnDSA. All samples were tested for IgG 1:3 dilution, IgG subclasses (IgG3 and IgG4), and IgG C1q. Samples at dnDSA onset were also tested at IgG1:10 dilution and for IgM.

Results: At the time of dnDSA onset, IgG subclass and C1q testing did not distinguish those at increased risk of graft loss (Fig 1a). A dilution of 1:10 at dnDSA onset was correlated with an increased risk of eventual graft loss 4.6 times compared to DSA IgG 1:10 (-) patients. There was a trend toward IgM dnDSA at onset being a characteristic that correlates with development of acute rejection within 1 year post-dnDSA (p=0.06). Looking into testing beyond dnDSA onset, patients having C1q at 6 months were at a very high risk for graft loss. Finally, those with IgG3 DSA at 12 months post-dnDSA were also at a very high risk for graft loss. The overall trend in the progression of positivity in these patients is the following (Fig 1b): many patients have IgG4 at the time of DSA onset. Those who develop IgG3 and/or C1q (+) DSA are most likely to progress to graft failure.

Conclusions: Using IgG dilutions, IgM, IgG subclass, and IgG C1q testing can help improve the prediction of graft loss in dnDSA positive patients.

CITATION INFORMATION: Everly M, Rebellato L, Haisch C, Briley K, Bolin P, Kendrick S, Morgan C, Maldonado A, Nguyen A, Terasaki P. IgG Dilutions, Subclasses, C1q, and IgM: Determining Relevant Testing for De Novo DSA and Outcome Prediction. Am J Transplant. 2016;16 (suppl 3).

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