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Journal of Immunology Research
Volume 2017, Article ID 1652931, 14 pages
Research Article

Renal Transplant Patients Biopsied for Cause and Tested for C4d, DSA, and IgG Subclasses and C1q: Which Humoral Markers Improve Diagnosis and Outcomes?

1VRL Eurofins, Los Angeles, CA, USA
2MNIT Foundation, Los Angeles, CA, USA
3USC Keck School of Medicine, Los Angeles, CA, USA
4Western University of Health Sciences, Pomona, CA, USA
5University of Miami, Miami, FL, USA
6BloodSource, Mather, CA, USA
7UC Davis School of Medicine, Sacramento, CA, USA
8CNSU College of Medicine, Elk Grove, CA, USA
9St. Vincent Medical Center, Los Angeles, CA, USA
10Transplant Research Institute, Los Angeles, CA, USA

Correspondence should be addressed to Nathan A. Lemp; moc.sniforue-lrv@pmelnahtan

Received 3 October 2016; Accepted 5 December 2016; Published 15 January 2017

Academic Editor: Frans H. J. Claas

Copyright © 2017 James C. Cicciarelli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The association between donor specific antibodies (DSA) and renal transplant rejection has been generally established, but there are cases when a DSA is present without rejection. We examined 73 renal transplant recipients biopsied for transplant dysfunction with DSA test results available: 23 patients diffusely positive for C4d (C4d+), 25 patients focally positive for C4d, and 25 patients negative for C4d (C4d−). We performed C1q and IgG subclass testing in our DSA+ and C4d+ patient group. Graft outcomes were determined for the C4d+ group. All 23 C4d+ patients had IgG DSA with an average of 12,500 MFI (cumulative DSA MFI). The C4d− patients had average DSA less than 500 MFI. Among the patients with C4d+ biopsies, 100% had IgG DSA, 70% had C1q+ DSA, and 83% had complement fixing IgG subclass antibodies. Interestingly, IgG4 was seen in 10 of the 23 recipients’ sera, but always along with complement fixing IgG1, and we have previously seen excellent function in patients when IgG4 DSA exists alone. Cumulative DSA above 10,000 MFI were associated with C4d deposition and complement fixation. There was no significant correlation between graft loss and C1q positivity, and IgG subclass analysis seemed to be a better correlate for complement fixing antibodies in the C4d+ patient group.