ABSTRACT
Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT.
Subject(s)
HLA Antigens , Hematopoietic Stem Cell Transplantation , Isoantibodies , Humans , Hematopoietic Stem Cell Transplantation/methods , Male , Female , Adult , Retrospective Studies , Middle Aged , HLA Antigens/immunology , Isoantibodies/blood , Isoantibodies/immunology , Tissue Donors , Graft Rejection/immunology , Plasma Exchange/methods , Adolescent , Transplantation, Haploidentical/methods , Young Adult , Biomarkers/blood , Desensitization, Immunologic/methodsABSTRACT
Organisms sensing environmental cues and internal states and integrating the sensory information to control fecundity are essential for survival and proliferation. The present study finds that a moderate cold temperature of 11°C reduces egg laying in Caenorhabditis elegans. ASEL and AWC neurons sense the cold via GCY-20 signaling and act antagonistically on egg laying through the ASEL and AWC/AIA/HSN circuits. Upon cold stimulation, ASEL and AWC release glutamate to activate and inhibit AIA interneurons by acting on highly and lowly sensitive ionotropic GLR-2 and GLC-3 receptors, respectively. AIA inhibits HSN motor neuron activity via acetylcholinergic ACR-14 receptor signaling and suppresses egg laying. Thus, ASEL and AWC initiate and reduce the cold suppression of egg laying. ASEL's action on AIA and egg laying dominates AWC's action. The biased opposite actions of these neurons on egg laying provide animals with a precise adaptation of reproductive behavior to environmental temperatures.