Background: Antibody-mediated rejection (ABMR) is a major obstacle for successful transplant in HS patients. TCZ has anti-B cell and anti-inflammatory properties. We have reported its successful use for pre-transplant (Tx) desensitization (DES) and treatment of ABMR. Complement- (CDC) and antibody-dependent cellular cytotoxicity (ADCC) are the primary mechanisms for ABMR and mediated primarily by IgG1 & 3 subclasses. Here we measured the IgG1-4 in patients treated with TCZ to assess its effect on these subclasses.

Methods: Archived plasma or serum samples obtained pre- and post-Rx (up to 24M post-Rx) from 16 TCZ and 18 rituximab (RIT, Control)-Rx patients were tested for IgG subclass by luminex. Of 16 TCZ (8mg/kg, 6x, monthly) patients, 5 received TCZ as DES followed by Tx, and the remaining did so only post-Tx. All RIT patients received RIT as DES w/ or wo/ additional RIT post-Tx. The IgG levels pre- (0M) vs. post-Rx (6, 9 and 12M) was compared in both groups. The normal cut-off for IgG1, 2, 3 & 4 as analyzed by the luminx were 331, 281, 51 and 12ng/ml.

Results: The average IgG1, 2, 3 and 4 levels were 260±136, 120±54, 397±549 and 14±15 in TCZ, and 207±85, 100±54, 62±36 and 19±52 in RIT patients, respectively. Most RIT patients showed normal levels of IgG1, 2 and 4 pre-Rx, while IgG3 levels were elevated in 60% of the patients. In contrast, IgG1 & 4 in 30% and IgG3 in 60% of TCZ patients were elevated, while all showed normal IgG2 levels. In the TCZ group, the levels of all the IgG subclasses decreased at 6M post-1^st TCZ (end of the Rx) to normal levels in all or most patients (IgG1: 260±136 to 137±68 ng/ml, p=0.032, IgG2: 120±54 to 63±27 ng/ml, p=0.01, IgG3: 397±549 to 27±42 ng/ml, p=0.085, IgG4: 14±15 to 4±4 ng/ml, p=0.123). These lowered levels tended to remain up to 12M post-Rx, but this was not statistically significant. No consistent change in IgG subclass levels was observed post-RIT-Rx.

Conclusions: IgG1, 3 & 4 levels are elevated in many HS patients, which might be one of reasons for a high risk for ABMR in HS patients. TCZ-Rx reduces all 4 IgG subclass levels by 6M post-1^st TCZ to normal levels and the lowered levels tend to remain up to 12M post-Rx. This suggests that TCZ could reduce both CDC and ADCC-mediated ABMR through reduction of IgG1 & 3 subclasses.

CITATION INFORMATION: Shin B.-H, Ge S, Choi J, Kahwaji J, Vo A, Petrosyan A, Jordan S, Toyoda M. The Effect of Tocilizmab Treatment (TCZ-Rx) on IgG Subclasses in HLA-sensitized (HS) Kidney Transplant Patients Treated with TCZ. Am J Transplant. 2016;16 (suppl 3).

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