P133 C1q single antigen bead testing: A case with questionable significance?

Abstract

A 2 year old boy received a compatible haplotype-matched LD kidney transplant from his father. Routine monitoring by Luminex Single Antigen Bead (SAB) testing detected a de novo Donor Specific Antibody (DSA) against DQ7/DQA1 ∗ 05 6 months after transplant. Clinical and biopsy results showed no overt C4d deposition or other evidence of rejection. The patient was placed on Intravenous immunoglobulin (IVIG) therapy and enhanced monitoring as a precautionary measure. Over the next 9 months, the DSA continued to become stronger despite a lack of any other signs of rejection. The IVIG was discontinued after 6 months of treatment, due to recurrent mild to moderate infusion reactions. The clinical team contemplated treating the patient with combinations of rituximab, bortezomib, and plasmapheresis because of the patient’s young age, increased sensitization, and published reports showing that DSA could lead to decreased graft survival despite no overt acute rejection episodes. C1q DSA testing was performed due to recent literature suggesting that a C1q-positive DSA imparts a much shorter graft survival time. Additional characterization of the DSA was pursued to determine which IgG subclasses contributed to the strong DSA reading. C1q and total IgG SAB results were concordant, while the IgG subclass SAB testing results demonstrated a strong IgG4 subclass DSA and negligible contributions of the other 3 IgG subclasses. C1q and total IgG results were discordant with the clinical and biopsy findings, whereas the subclass testing provides support for IgG4 DSA having limited negative impact on allografts. DSA results are seen in Fig. 1. It is generally accepted that C1q-SAB positive DSA impart a much worse prognosis partly because it signifies potent IgG1 and/or IgG3 subclasses are present. This cases demonstrates that C1q binding can occur in vitro with high levels of IgG4 and therefore might lack clinical significance. The patient remains under observation, and no additional desensitization is currently considered.