Wong Jackson Y, Tait Brian, Levvey Bronwyn, Griffiths Anne, Esmore Donald S, Snell Gregory I, Williams Trevor J, Kotsimbos Tom C
Heart and Lung Transplant Service, The Alfred Hospital, Prahran, Melbourne, Victoria 3181, Australia.
Transplantation. 2004 Jul 27;78(2):205-10. doi: 10.1097/01.tp.0000128611.71038.0c.
Posttransplant lymphoproliferative disease (PTLD) in lung transplant recipients (LTRs) is potentially lethal with considerable morbidity. The role of donor (D)/recipient (R) HLA matching is unknown.
We reviewed our LTRs from January 1994, when routine D/R Epstein-Barr virus (EBV) serologic screening was begun, through to January 2000. We examined whether D/R HLA match status influenced the risk of PTLD in EBV D+/R- mismatched LTRs.
There were 16 D+/R- EBV-mismatched LTRs, 5 (31%) of whom developed PTLD (from a total of 237 LTRs; 218 survived >30 days). There were only two other cases of PTLD among the non-EBV primary mismatched patients. All patients received baseline immunosuppression of cyclosporine, azathioprine, and prednisolone without cytolytics and ganciclovir prophylaxis if "at risk" from cytomegalovirus. The five PTLD cases were diagnosed 81 to 734 (median 116) days from transplantation; three involved the lung allograft and two others involved lymph nodes. All PTLD patients seroconverted for EBV, whereas 7 of the 11 remaining EBV-mismatched patients who did not develop PTLD did not seroconvert. In the 16 EBV primary mismatched patients, there were 4 of 66 HLA allele matches in the 11 PTLD-free patients versus 15 of 30 matches in the 5 PTLD patients (P<0.001). This resulted in 2 or more HLA (A/B/DR) matches in 4 of 5 patients with PTLD versus 0 of 11 in the PTLD-free group (P=0.003). All PTLD patients were treated with reduced immunosuppression and antiviral therapy. Only two of the five LTRs who developed PTLD died, one with progressive disease despite chemotherapy and the other from chronic allograft rejection.
A high degree of HLA matching in D/R EBV-mismatched LTRs significantly increases the risk of PTLD.
肺移植受者（LTRs）中的移植后淋巴细胞增生性疾病（PTLD）具有潜在致死性，且发病率颇高。供体（D）/受体（R）人类白细胞抗原（HLA）匹配的作用尚不清楚。
我们回顾了1994年1月至2000年1月期间的LTRs，此期间开始进行常规的D/R Epstein-Barr病毒（EBV）血清学筛查。我们研究了D/R HLA匹配状态是否会影响EBV D+/R-不匹配的LTRs发生PTLD的风险。
有16例EBV D+/R-不匹配的LTRs，其中5例（31%）发生了PTLD（在总共237例LTRs中；218例存活超过30天）。在非EBV初次不匹配的患者中仅有另外2例PTLD病例。所有患者均接受了环孢素、硫唑嘌呤和泼尼松龙的基础免疫抑制治疗，若有巨细胞病毒“风险”则未使用细胞溶解剂和更昔洛韦进行预防。5例PTLD病例在移植后81至734天（中位时间116天）被诊断；3例累及肺移植器官，另外2例累及淋巴结。所有PTLD患者EBV血清学转换，而其余11例未发生PTLD的EBV不匹配患者中有7例未发生血清学转换。在16例EBV初次不匹配的患者中，11例无PTLD的患者中有66个HLA等位基因匹配中的4个，而5例PTLD患者中有30个匹配中的15个（P<0.001）。这导致5例PTLD患者中有4例有2个或更多HLA（A/B/DR）匹配，而无PTLD组的11例患者中为0例（P=0.003）。所有PTLD患者均接受了免疫抑制减量和抗病毒治疗。发生PTLD的5例LTRs中仅有2例死亡，1例尽管接受化疗仍病情进展，另1例死于慢性移植排斥反应。
D/R EBV不匹配的LTRs中高度的HLA匹配显著增加了PTLD的风险。
