Arbon Kate S, Albers Erin, Kemna Mariska, Law Sabrina, Law Yuk
School of Medicine.
Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington.
J Heart Lung Transplant. 2015 Aug;34(8):1103-11. doi: 10.1016/j.healun.2015.03.014. Epub 2015 Mar 27.
Allograft rejection and long-term immunosuppression remain significant challenges in pediatric heart transplantation. Pediatric recipients are known to have fewer rejection episodes and to develop more allergic conditions than adults. A T-helper 2 cell dominant phenotype, manifested clinically by allergies and an elevated eosinophil count, may be associated with immunologic quiescence in transplant recipients. This study assessed whether the longitudinal eosinophil count and an allergic phenotype were associated with freedom from rejection.
This single-center, longitudinal, observational study included 86 heart transplant patients monitored from 1994 to 2011. Post-transplant biannual complete blood counts, allergic conditions, and clinical characteristics related to rejection risk were examined.
At least 1 episode of acute cellular rejection (ACR) occurred in 38 patients (44%), antibody-mediated rejection (AMR) occurred in 11 (13%), and 49 patients (57%) were diagnosed with an allergic condition. Patients with ACR or AMR had a lower eosinophil count compared with non-rejectors (p = 0.011 and p = 0.022, respectively). In the multivariable regression analysis, the presence of panel reactive antibodies to human leukocyte antigen I (p = 0.014) and the median eosinophil count (p = 0.011) were the only independent covariates associated with AMR. Eosinophil count (p = 0.010) and female sex (p = 0.009) were independent risk factors for ACR. Allergic conditions or young age at transplant were not protective from rejection.
This study demonstrates a novel association between a high eosinophil count and freedom from rejection. Identifying a biomarker for low rejection risk may allow a reduction in immunosuppression. Further investigation into the role of the T-helper 2 cell phenotype and eosinophils in rejection quiescence is warranted.
同种异体移植排斥反应和长期免疫抑制仍是小儿心脏移植中的重大挑战。已知小儿心脏移植受者的排斥反应发作次数少于成人，但发生过敏情况的更多。以过敏和嗜酸性粒细胞计数升高为临床特征的辅助性T2细胞主导表型，可能与移植受者的免疫静止有关。本研究评估了嗜酸性粒细胞计数的纵向变化及过敏表型是否与无排斥反应相关。
这项单中心、纵向、观察性研究纳入了1994年至2011年期间接受监测的86例心脏移植患者。对移植后的血常规、过敏情况以及与排斥反应风险相关的临床特征进行了每半年一次的检查。
38例患者（44%）发生了至少1次急性细胞排斥反应（ACR），11例（13%）发生了抗体介导的排斥反应（AMR），49例患者（57%）被诊断患有过敏症。与未发生排斥反应的患者相比，发生ACR或AMR的患者嗜酸性粒细胞计数较低（分别为p = 0.011和p = 0.022）。在多变量回归分析中，针对人类白细胞抗原I的群体反应性抗体的存在（p = 0.014）和嗜酸性粒细胞计数中位数（p = 0.011）是与AMR相关的仅有的独立协变量。嗜酸性粒细胞计数（p = 0.010）和女性性别（p = 0.009）是ACR的独立危险因素。过敏情况或移植时年龄较小并不能预防排斥反应。
本研究证明了嗜酸性粒细胞计数高与无排斥反应之间存在一种新的关联。确定低排斥反应风险的生物标志物可能有助于减少免疫抑制。有必要进一步研究辅助性T2细胞表型和嗜酸性粒细胞在排斥反应静止中的作用。
