De-novo donor-specific anti-HLA antibodies 30 days after lung transplantation are associated with a worse outcome

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• 作者：Jé ; rô ; me Le Pavec ; MD ; PhD^a ; ^b ; ^c ; ^{lepavec@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Caroline Suberbielle ; MD^d ; Lilia Lamrani^a ; ^c ; Sé ; verine Feuillet ; MD^a ; ^b ; ^c ; Laurent Savale ; MD ; PhD^a ; ^c ; ^e ; Peter Dorfmü ; ller ; MD ; PhD^a ; ^c ; ^f ; Franç ; ois Stephan ; MD^a ; ^c ; ^g ; Sacha Mussot ; MD^a ; ^b ; ^c ; Olaf Mercier ; MD ; PhD^a ; ^b ; ^c ; Elie Fadel ; MD ; PhD^a ; ^b ; ^c
• 关键词：lung transplantation ; de-novo donor-specific antibodies ; antibody mediated rejection ; chronic lung allograft dysfunction ; survival
• 刊名：Journal of Heart and Lung Transplantation
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：35
• 期：9
• 页码：1067-1077
• 全文大小：441 K

文摘

The impact of de-novo donor-specific anti-HLA antibodies (DSA) on patient and graft survival after lung transplantation remains controversial. We analyzed DSA that developed at Day 7 and Month (M) 1, M3, M6 and M12 after lung transplantation and evaluated their impact on chronic lung allograft dysfunction (CLAD) development and survival.

Methods

One hundred thirty-four patients who underwent lung transplantation at our institution between November 2007 and August 2013 were included in this study. During the first post-transplant year, 82 (61%) patients developed de novo DSA and 52 (39%) patients did not. Three mean fluorescence intensity (MFI) intervals were used to define scores of anti-HLA antibody positivity: score 4 if MFI was 500 to 1,000; score 6 if MFI was 1,000 to 3,000; and score 8 if MFI was ≥3,000. Patients’ records were retrospectively reviewed.

Results

DSA with MFI scores of ≥4 (hazard ratio [HR] 2.21, 95% confidence interval [CI] 1.08 to 4.54, p = 0.03), 6 (HR 2.63, 95% CI 1.27 to 5.20, p < 0.01) and 8 (HR 2.83, 95% CI 1.42 to 5.67, p < 0.01) at M1; female gender (HR 0.49, 95% CI 0.28 to 0.87, P = 0.01); and with post-operative extracorporeal membrane oxygenation (HR 0.09, 95% CI 0.01 to 0.28, p = 0.02) were significantly associated with CLAD. Multivariate analysis identified score 8 at M1 (HR 2.71, 95% CI 1.34 to 5.47, p < 0.01) as an independent risk factor for mortality. Overall, 1-, 3- and 5-year survival rates were 76%, 52% and 41% compared with 84%, 74% and 70% for patients with or without de-novo DSA at M1, respectively (p = 0.02).

Conclusion

Early de-novo DSA may significantly impact long-term outcomes after lung transplantation and should therefore prompt regular screening.