Complement (C1q) fixing solid-phase screening for HLA antibodies increases the availability of compatible platelet components for refractory patients

Abstract

Background: Immune refractoriness to platelet (PLT) transfusion is primarily due to HLA antibody. Patients at our institution are identified as refractory due to HLA by a Luminex-based immunoglobulin (Ig)G-single-antigen-bead (SAB) assay, but in highly sensitized patients, antigen-negative compatible donors cannot be found due to the high sensitivity of the IgG-SAB method. We developed an assay that detects only HLA antibodies binding the first complement component (C1q). We hypothesized that the C1q-SAB method might be more relevant than the IgG-SAB method because the antibodies identified may activate the complement cascade causing PLT destruction.

Study design and methods: Thirteen highly sensitized refractory patients received 177 PLT units incompatible by the IgG-SAB method. They were retrospectively retested by the C1q-SAB method. Calculated percent reactive antibody (CPRA) and HLA antibody specificities were compared between the two methods and corrected count increment (CCI) values were analyzed. Additionally the impact of ABO compatibility on CCI responses was evaluated.

Results: The mean CPRA value was significantly lower by C1q-SAB (60%) than by IgG-SAB (94%; p < 0.05). Patients showed significantly better CCI (10.6 × 10(9) ± 0.8 × 10(9) /L) with C1q-compatible (n = 134) than with C1q-incompatible PLTs (n = 43) (2.5 × 10(9) ± 0.9 × 10(9) /L/m(2) ; p < 0.0001). ABO compatibility did not significantly impact the CCI values (p < 0.0001). Our results show that 75% of PLT units previously considered incompatible were actually compatible.

Conclusion: For highly refractory patients to PLT transfusion, the C1q-based SAB binding assay may be a better method for identifying clinically relevant HLA antibodies and selecting PLT units that will result in acceptable CCI.