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ORIGINAL ARTICLE Impact of Pretransplant Anti-HLA Antibodies on Outcomes in Lung Transplant Candidates Miae Kim1,2 , Keri R.

Townsend2,3 , Isabelle G. Wood4 , Steve Boukedes3 , Indira Guleria4,5,6 , Steven Gabardi2,5,6,7 , Souheil El-Chemaly3,5 , Phillip C. Camp5,8 , Anil K. Chandraker5,6 , Edgar L. Milford4,5,6 , and Hilary J. Goldberg3,5

1 Heart Transplant Program, Center for Advanced Heart Disease, Department of Medicine,

2 Department of Pharmacy Services,

3 Lung Transplant Program, Division of Pulmonary and Critical Care Medicine, Department of Medicine,

4 Tissue Typing Lab,

6 Renal Division,

7 Department of Transplant Surgery, and

8 Lung Transplant Program, Division of Thoracic Surgery, Brigham and Women'

s Hospital, Boston, Massachusetts;

and

5 Harvard Medical School, Boston, Massachusetts Abstract Rationale: The prevalence of anti-HLA antibodies in lung transplant candidates and their impact on waitlist and transplant outcomes is not known. Objectives: We examined the prevalence of pretransplant anti-HLA antibodies at varying thresholds and evaluated their impact on outcomes before and after lung transplantation. Methods: We performed a single-center retrospective cohort study including all patients listed for lung transplantation between January

2008 and August 2012. Per protocol, transplant candidates were assessed by solid phase LABscreen mixed Class I and II and LABscreen Single Antigen assays. Measurements and Main Results: Among

224 patients, 34% had anti-HLA antibodies at mean ?uorescent intensity (MFI) greater than or equal to 3,000 (group III), and 24% had antibodies at MFI 1,000 to3,000(groupII).Ninetypercentofthepatientswithpretransplantanti- HLA antibodies had class I antibodies, whereas only seven patients developed class II alone. Patients in group III were less likely to receive transplants than patients without any anti-HLA antibodies (group I) (45.5vs.67.7%,P=0.005).WaittimetotransplantwaslongeringroupIII thangroup I,although this differencedid notmeet statistical signi?cance, and waitlist mortality was similar. Among transplant recipients, antibody-mediated rejection(AMR)was morefrequentin group III than in group II (20% vs. 0%, P = 0.01) or group I (6.3%, P = 0.05). Conclusions: The presence of anti-HLA antibodies at the high MFI threshold (.3,000) was associated with lower transplant rate and higher rates of AMR. Screening for anti-HLA antibodies using the 3,000 MFI threshold may be important in managing transplant candidates and recipients. Keywords: HLA antigens;

histocompatibility testing;

transplantation At a Glance Commentary Scienti?c Knowledge on the Subject: Although the effect of circulating anti-HLA antibodies on post-transplant outcomes in solid organ transplant recipients has been studied, the impact of pretransplant circulating anti-HLA antibodies on the outcomes of lung transplant candidates has not been explored. What This Study Adds to the Field: Our study shows that the presence of anti-HLA antibodies at high mean ?uorescent intensity threshold (.3,000) before transplant is negatively associated with transplant rate in patients awaiting lung transplant and with increased risk for antibody-mediated rejection in transplant recipients. (Received in original form December 9, 2014;

accepted in ?nal form April 16, 2014) Author Contributions: M.K. was involved in study design, data collection, interpretation, analysis, and writing the manuscript. K.R.T. and H.J.G. were involved in study design, data interpretation, analysis, and manuscript revision. I.G.W., S.B., and I.G. were involved in data collection and data interpretation. A.K.C. and E.L.M. were involved in study design and data interpretation. S.E.-C. and P.C.C. were involved in data interpretation and data analysis. S.G. was involved in data interpretation and statistical analysis. All authors contributed to the ?nal version of the article and approved the ?nal version to be published. Correspondence and requests for reprints should be addressed to Hilary J. Goldberg, M.D., M.P.H., Division of Pulmonary and Critical Care Medicine, Brigham and Women'