N Suciu-Foca

Columbia University, New York City, New York, United States

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Publications (200)1079.2 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Presensitization against a broad array of HLA is associated with prolonged waiting times and inferior kidney allogaft survival. Although the use of solid phase assay (SPA) for the detection and characterization of anti-HLA antibodies provides greater sensitivity than complement-dependent lymphocytotoxicity (CDC) assay, it often detects donor specific antibodies (DSA) which turn out to be clinically irrelevant. Our data reinforce the concept that these two types of assays should be used in parallel for pre-and post-transplantation monitoring of anti-HLA antibodies in recipients of solid organ allografts.
    Human immunology 01/2014; · 2.55 Impact Factor
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    ABSTRACT: BACKGROUND: The introduction of solid-phase immunoassay (SPI) technology for the detection and characterization of human leukocyte antigen (HLA) antibodies in transplantation while providing greater sensitivity than was obtainable by complement-dependent lymphocytotoxicity (CDC) assays has resulted in a new paradigm with respect to the interpretation of donor-specific antibodies (DSA). Although the SPI assay performed on the Luminex instrument (hereafter referred to as the Luminex assay), in particular, has permitted the detection of antibodies not detectable by CDC, the clinical significance of these antibodies is incompletely understood. Nevertheless, the detection of these antibodies has led to changes in the clinical management of sensitized patients. In addition, SPI testing raises technical issues that require resolution and careful consideration when interpreting antibody results. METHODS: With this background, The Transplantation Society convened a group of laboratory and clinical experts in the field of transplantation to prepare a consensus report and make recommendations on the use of this new technology based on both published evidence and expert opinion. Three working groups were formed to address (a) the technical issues with respect to the use of this technology, (b) the interpretation of pretransplantation antibody testing in the context of various clinical settings and organ transplant types (kidney, heart, lung, liver, pancreas, intestinal, and islet cells), and (c) the application of antibody testing in the posttransplantation setting. The three groups were established in November 2011 and convened for a "Consensus Conference on Antibodies in Transplantation" in Rome, Italy, in May 2012. The deliberations of the three groups meeting independently and then together are the bases for this report. RESULTS: A comprehensive list of recommendations was prepared by each group. A summary of the key recommendations follows. Technical Group: (a) SPI must be used for the detection of pretransplantation HLA antibodies in solid organ transplant recipients and, in particular, the use of the single-antigen bead assay to detect antibodies to HLA loci, such as Cw, DQA, DPA, and DPB, which are not readily detected by other methods. (b) The use of SPI for antibody detection should be supplemented with cell-based assays to examine the correlations between the two types of assays and to establish the likelihood of a positive crossmatch (XM). (c) There must be an awareness of the technical factors that can influence the results and their clinical interpretation when using the Luminex bead technology, such as variation in antigen density and the presence of denatured antigen on the beads. Pretransplantation Group: (a) Risk categories should be established based on the antibody and the XM results obtained. (b) DSA detected by CDC and a positive XM should be avoided due to their strong association with antibody-mediated rejection and graft loss. (c) A renal transplantation can be performed in the absence of a prospective XM if single-antigen bead screening for antibodies to all class I and II HLA loci is negative. This decision, however, needs to be taken in agreement with local clinical programs and the relevant regulatory bodies. (d) The presence of DSA HLA antibodies should be avoided in heart and lung transplantation and considered a risk factor for liver, intestinal, and islet cell transplantation. Posttransplantation Group: (a) High-risk patients (i.e., desensitized or DSA positive/XM negative) should be monitored by measurement of DSA and protocol biopsies in the first 3 months after transplantation. (b) Intermediate-risk patients (history of DSA but currently negative) should be monitored for DSA within the first month. If DSA is present, a biopsy should be performed. (c) Low-risk patients (nonsensitized first transplantation) should be screened for DSA at least once 3 to 12 months after transplantation. If DSA is detected, a biopsy should be performed. In all three categories, the recommendations for subsequent treatment are based on the biopsy results. CONCLUSIONS: A comprehensive list of recommendations is provided covering the technical and pretransplantation and posttransplantation monitoring of HLA antibodies in solid organ transplantation. The recommendations are intended to provide state-of-the-art guidance in the use and clinical application of recently developed methods for HLA antibody detection when used in conjunction with traditional methods.
    Transplantation 12/2012; · 3.78 Impact Factor
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    ABSTRACT: The present study describes two new HLA-D specificities: LD13, associated with DR1, and LD14 associated with DR2. LD13 is defined by an HTC who is the bc offspring of an a: A25, B18, DR7, Dw7/b: A33, B14, DR1, Dx father, and of a c: A24, B14, DR1, Dx/d: A26, B41, DR5, Dw5 mother. This HTC was included both as a responder and as a stimulator in our cross-reference studies of 8W HTCs. While failing to cluster with any other 8W HTC, it typed 2 of 64 panel members carrying a “blank” HLA-D, linked to DR1. To exclude the possibility that HTC-LD13 might be a split of Dw1, the entire family was tested with the Family Set of 8W HTCs. No typing responses to any 8W Dw1 HTCs were observed. Furthermore, checkerboard experiments between HTC-LD 13 and 8W Dw1 HTCs showed strong reciprocal stimulation. The LD13 specificity was only found in Ashkenazi Jews and may be in linkage disequilibrium with HLA-B14. LD14 is defined by three, SD different, HTCs deriving from the same family of Sicilian descent. The family was included in the 8th Workshop and each HTC was shown to have inherited DR2, MT1 from both parents. When tested as stimulators, on our HLA-D reference panel, these cells were clustered in a distinct group, LD14, associated with DR2. None of the 8W HTCs appeared to belong to this cluster. The antigen frequency of LD14 is 0.03.
    Tissue Antigens 12/2008; 17(3):294 - 302. · 2.93 Impact Factor
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    ABSTRACT: To assess the significance of antibodies detected by complement-dependent cytotoxicity (CDC), solid phase (SPA) and flow cytometry (FC) assays we compared their predictive value in 354 consecutive cases of deceased-donor kidney transplantation. Pre-transplantation screening of anti-HLA class I and class II antibodies was performed by CDC and SPA. The direct crossmatch between recipients' sera and donors' T and B cells was performed by CDC followed by FC and SPA ("virtual cross-match"). The past history of antibodies displayed by the recipient was not considered a contraindication for transplantation even when it showed DSA. A side-by-side comparison of the correlation between graft loss, history of DSA and cross-match results indicated that sensitivity was 5%, 16% and 17% while specificity was 99%, 93% and 86% in CDC, SPA, FC crossmatches respectively. There was no significant difference between the 3 year survival of primary and secondary kidney allografts. We conclude that screening and cross-matching the sera by CDC provides reliable results and optimizes the patient's chances to receive a transplant. SPA and FC, however, are of great importance for identifying patients which require close monitoring by biopsy and serology for early diagnosis and treatment of acute antibody mediated rejection (AAMR).
    Transplant Immunology 11/2008; 20(1-2):61-7. · 1.52 Impact Factor
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    ABSTRACT: The interleukin-2 receptor alpha chain (IL-2Ra, CD25) plays a major part in shaping the dynamics of T cell populations following immune activation, due to its role in T cell proliferation and survival. Strategies to blunt the effector responses in transplantation have been developed by devising pharmaceutical agents to block the IL-2 pathways. However, such strategies could adversely affect the CD25(+)FOXP3(+)T regulatory (T reg) populations which also rely on intereukin-2 signaling for survival. The present study shows that a cohort of heart allograft recipients treated with Daclizumab (a humanized anti-CD25 antibody) display FOXP3 expression patterns consistent with functional T regulatory cell populations. High levels of FOXP3 were observed to correlate with lower incidence of and recovery from acute rejection, as well as lower levels of anti-donor HLA antibody production. Therefore, T reg populations appear fully functional in patients treated with Daclizumab, even when 5 doses were administered. By comparison, patients treated with fewer doses or no Daclizumab had a higher incidence of acute rejection, antibody production and graft failure. Therefore, our data indicates that Daclizumab treatment does not interfere with the generation of regulatory T cells and has a beneficial effect on heart allograft survival.
    Transplant Immunology 08/2007; 18(1):13-21. · 1.52 Impact Factor
  • Journal of Heart and Lung Transplantation - J HEART LUNG TRANSPLANT. 01/2007; 26(2).
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    ABSTRACT: Immunoglobulin-like transcript (ILT)-3 is a transmembrane receptor, which belongs to the immunoglobulin superfamily. In previous studies, we showed that allospecific CD8+CD28- T suppressor cells (Ts) induce the expression of ILT3 in human endothelial cells (EC) rendering them tolerogenic. Using a polymerase chain reaction (PCR)-based approach, we now demonstrate by cell fractionation and sequencing studies that ILT3 precursor RNA is expressed and retained in nuclei of resting EC. Ts interaction with EC or exposure of EC to interleukin-10 (IL-10) and interferon alpha (IFN-alpha) triggers processing of ILT3 pre-mRNA. Western blot analysis showed that the expression of the mature ILT3 transcript is accompanied by production of ILT3 protein.
    American Journal of Transplantation 02/2006; 6(1):76-82. · 6.19 Impact Factor
  • Journal of Heart and Lung Transplantation - J HEART LUNG TRANSPLANT. 01/2005; 24(2).
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    ABSTRACT: CD8+CD28- human T-suppressor cells (Ts), which can be generated in vitro, act directly on APC rendering them tolerogenic to unprimed and primed CD4+ T cells. The aim of this study was to investigate the possibility that CD8+ T cells mediate the induction of tolerance in a heart transplantation model in rodents. Blood from Lewis rats was UV-B-irradiated and transfused into ACI recipients on days -21, -14, and -7 before heart allograft transplantation on day 0. CD4(+) and CD8(+) T cells were positively selected from ACI rats, which had tolerated Lewis heart allografts for more than 100 days and were adoptively transferred to naive ACI rats pretreated (day -1) with gamma irradiation. These ACI rats underwent transplantation with Lewis hearts 24 hours after adoptive transfer of putative T-suppressor cells. Adoptive transfer of CD8(+) T cells from tolerant ACI to naive ACI rats significantly prolonged Lewis heart mean allograft survival time (MST +/- SD) to 69 +/- 13 days as compared with 15 +/- 1 and 14 +/- 1 days in animals adoptively transferred with CD4+ T cells or untreated controls, respectively (P < .001). Similarly, adoptive transfer of CD8(+) T cells from secondary ACI recipients to naive syngeneic animals also significantly prolonged survival of heart allografts to MST +/- SD of 72 +/- 4 for CD8(+) and 15 +/- 4 days for CD4(+) T cells (P < .001). These data demonstrate that allogeneic tolerance induced in ACI recipients by treatment with UV-B-irradiated blood from Lewis donors is mediated by CD8+ T-suppressor cells.
    Transplantation Proceedings 01/2005; 37(1):43-5. · 0.95 Impact Factor
  • Transplantation 01/2004; 78. · 3.78 Impact Factor
  • Transplantation 01/2004; 78. · 3.78 Impact Factor
  • Human Immunology - HUM IMMUNOL. 01/2004; 65(9):1057-1060.
  • Transplantation 01/2004; 78. · 3.78 Impact Factor
  • Transplantation 01/2004; 78. · 3.78 Impact Factor
  • Transplantation 01/2004; 78. · 3.78 Impact Factor
  • Journal of Heart and Lung Transplantation - J HEART LUNG TRANSPLANT. 01/2003; 22(1).
  • Gilberto Filaci, Nicole Suciu-Foca
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    ABSTRACT: The CD8+ T suppressor lymphocytes identified in humans belong to three different subpopulations. All of them inhibit the proliferation of antigen-specific T cells. The type 1 and type 2 of CD8+ T suppressor cells are characterized by the CD8+CD28- phenotype, while no detailed data are available at the moment on the phenotype of the type 3 of CD8+ T suppressor cells. The type 1 of CD8+ suppressor T lymphocytes acts by inducing alteration of expression of co-stimulatory molecules on dendritic cells. A cell-to-cell contact is required to mediate this effect. The type 2 of CD8+ T suppressor cells induces inhibition via cytokine secretion (IFNgamma, IL6) and do not need to interact directly with antigen presenting cells. The type 3 of CD8+ T suppressor cells mediates its function through the secretion of IL10. The complexity and multiplicity of CD8+ T suppressor cell subsets suggests that these cells may have an important role in the regulation of the immune homeostasis, acting together with the CD4+ T regulatory cell subpopulations. The specificity of the functions of each of these suppressor/regulatory subsets in the immune network requires to be clarified to better understand the immune system, its functions and the possibilities to modulate its activities in the course of immune-mediated diseases.
    Autoimmunity Reviews 11/2002; 1(5):279-83. · 7.98 Impact Factor
  • Transplantation Proceedings 09/2002; 34(5):1828-9. · 0.95 Impact Factor
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    ABSTRACT: Immunoglobulin-like transcript 3 (ILT3) and ILT4 belong to a family of inhibitory receptors expressed by human monocytes and dendritic cells. We show here that CD8+CD28(-) alloantigen-specific T suppressor (TS) cells induce the up-regulation of ILT3 and ILT4 on monocytes and dendritic cells, rendering these antigen-presenting cells (APCs) tolerogenic. Tolerogenic APCs show reduced expression of costimulatory molecules and induce antigen-specific unresponsiveness in CD4+ T helper cells. Studies of human heart transplant recipients showed that rejection-free patients have circulating TS cells, which induce the up-regulation of ILT3 and ILT4 in donor APCs. These findings demonstrate an important mechanism of immune regulation.
    Nature Immunology 04/2002; 3(3):237-43. · 26.20 Impact Factor
  • Z Liu, B Yu, J Fan, R Cortesini, N Suciu-Foca
    Transplantation Proceedings 01/2001; 33(1-2):82-3. · 0.95 Impact Factor

Publication Stats

4k Citations
1,079.20 Total Impact Points

Institutions

  • 1975–2014
    • Columbia University
      • • Department of Pathology & Cell Biology
      • • College of Physicians and Surgeons
      • • Department of Surgery
      New York City, New York, United States
  • 2002
    • Università degli Studi di Genova
      Genova, Liguria, Italy
  • 1978–2001
    • CUNY Graduate Center
      New York City, New York, United States
  • 1998
    • New York University
      • Department of Surgery
      New York City, NY, United States
  • 1996–1998
    • Sapienza University of Rome
      Roma, Latium, Italy
    • New York Presbyterian Hospital
      New York City, New York, United States
  • 1977
    • New York Blood Center
      New York City, New York, United States