Intravascular macrophages in cardiac allograft biopsies for diagnosis of early and late antibody-mediated rejection

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• 作者：Marny Fedrigo ; MD ; PhD^a ; Giuseppe Feltrin ; MD ; PhD^a ; Francesca Poli ; MD^b ; Anna Chiara Frigo ; MSc^a ; Elena Benazzi ; MD^b ; Antonio Gambino ; MD^a ; Francesco Tona ; MD ; PhD^a ; Alida L.P. Caforio ; MD ; PhD^a ; Chiara Castellani ; PhD^a ; Giuseppe Toscano ; MD^a ; Gino Gerosa ; MD^a ; Gaetano Thiene ; MD^a ; Annalisa Angelini ; MD^a ; ^{annalisa.angelini@unipd.it}
• 关键词：antibody-mediated rejection ; intravascular macrophages ; heart transplantation ; immunohistochemistry ; anti-HLA antibodies ; C4d
• 刊名：The Journal of Heart and Lung Transplantation
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：32
• 期：4
• 页码：404-409
• 全文大小：394 K

文摘

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Background

The aim of our study was to evaluate the role of intravascular macrophages in the diagnosis of early and late antibody-mediated rejection (AMR) on endomyocardial biopsies (EMBs).

Methods

We reviewed 1,420 consecutive EMBs from 131 patients and selected 75 C4d⁺ EMBs. The C4d⁺ group was compared with a control group (66 patients) matched for age, gender, date of transplantation, follow-up, immunosuppressive regimen and primary heart disease. A total of 141 EMBs were evaluated. Immunoperoxidase staining for C4d and CD68 were performed. Post-transplant IgG anti-HLA reactivity was investigated by Luminex technology. Clinical data were also collected. Fourteen EMBs were available from 11 symptomatic AMR patients.

Results

Of the 141 EMBs evaluated, 53 were positive for intravascular macrophages (CD68); among them, 32 were also positive for C4d (32 of 53, 60.4 % ). Of the 88 CD68^? EMBs, 43 were also C4d⁺ (43 of 88, 48.9 % ). Of the 53 CD68⁺ EMBs, 30 EMBs were within the first year since transplantation (30 of 53, 57.8 % ), and among these 21 were also positive for C4d (21 of 30, 70.0 % ). In the late period, among the 23 CD68⁺ EMBs (23 of 53, 42.2 % ) 11 were also positive for C4d (11 of 23, 47.8 % ). In the early period, intravascular macrophages were more common in symptomatic (3 of 3, 100 % ) than asymptomatic (3 of 11, 27.3 % ) patients. Sensitivity and specificity of intravascular macrophages in predicting donor-specific antibodies (DSA) within the first year were 50.0 % and 100.0 % , respectively.

Conclusions

Intravascular macrophages predict C4d, DSA and symptoms early after transplantation; however, in the late period, they are unable to identify patients with circulating DSA, C4d and/or symptoms.