Carpenter Margaret C, Shrestha Sweta, Bharadwaj Pranay, Concetta Catalano, Sharma Shilpee, Weiner Joshua A, de Haan Noortje, Pongracz Tamas, Le Moine Alain, Holovska Vanda, Marchant Arnaud, Ackerman Margaret E
Thayer School of Engineering, Dartmouth College Hanover NH USA.
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College Hanover NH USA.
Hum Immunol. 2025 Mar;86(2):111247. doi: 10.1016/j.humimm.2025.111247. Epub 2025 Jan 30.
Donor Specific Antibodies (DSAs) are associated with a higher risk of Antibody Mediated Rejection (AMR). However, not all DSAs are pathogenic, and patients that raise DSAs have a wide spectrum of outcomes ranging from the complete absence of graft injury to severe AMR. Hence, characterization of both the qualitative features and titer of DSAs has the potential to predict AMR risk and treatment outcome for sensitized patients. Here, using HLA-A2+ cell-based assays, we investigate the qualitative features of immunoglobulin G (IgG) alloantibodies including Fc receptor binding properties and Fc-mediated effector function over time. Compared to seronegative controls, reactive antibodies in seropositive participants were predominantly IgG1, and exhibited elevated levels of binding to the receptors involved in Antibody Dependent Cellular Phagocytosis (ADCP) and Antibody Dependent Cellular Cytotoxicity (ADCC) activity. Further analysis of seropositive individuals revealed that these activities were predictive ofAMR status. Collectively, these results suggest a role for phagocytic and cytotoxic antibody effector functions of DSA in contributing to graft injury.
供者特异性抗体（DSA）与抗体介导的排斥反应（AMR）风险较高相关。然而，并非所有DSA都具有致病性，产生DSA的患者有广泛的转归范围，从完全没有移植物损伤到严重的AMR。因此，对DSA的定性特征和滴度进行表征有可能预测致敏患者的AMR风险和治疗结果。在此，我们使用基于HLA - A2 +细胞的检测方法，研究免疫球蛋白G（IgG）同种异体抗体的定性特征，包括随时间推移的Fc受体结合特性和Fc介导的效应器功能。与血清阴性对照相比，血清阳性参与者中的反应性抗体主要为IgG1，并表现出与参与抗体依赖性细胞吞噬作用（ADCP）和抗体依赖性细胞毒性（ADCC）活性的受体结合水平升高。对血清阳性个体的进一步分析表明，这些活性可预测AMR状态。总体而言，这些结果表明DSA的吞噬和细胞毒性抗体效应器功能在导致移植物损伤中起作用。
