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  1. Article ; Online: Harnessing Precision Medicine: HLA or Eplet Matching in Heart Transplantation.

    Defilippis, Ersilia M / Lacelle, Chantale / Garg, Sonia / Farr, Maryjane

    Journal of cardiac failure

    2023  Volume 30, Issue 2, Page(s) 373–375

    MeSH term(s) Humans ; Precision Medicine ; Heart Failure/surgery ; Heart Transplantation ; Graft Rejection/prevention & control ; Tissue Donors
    Language English
    Publishing date 2023-10-26
    Publishing country United States
    Document type Editorial
    ZDB-ID 1281194-4
    ISSN 1532-8414 ; 1071-9164
    ISSN (online) 1532-8414
    ISSN 1071-9164
    DOI 10.1016/j.cardfail.2023.09.010
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  2. Article ; Online: New Desensitization Strategy: Daratumumab for Highly Sensitized Pediatric Heart Transplant Candidate.

    Baez Hernandez, Nathanya / Butts, Ryan / Radel, Laura / Bano, Maria / Lantz, Jodie / Davies, Ryan / Lacelle, Chantale / Iqbal, Mehreen / Ellimuttil, Tracey

    Transplantation

    2023  Volume 107, Issue 10, Page(s) e271–e272

    MeSH term(s) Child ; Humans ; Antibodies, Monoclonal/therapeutic use ; Desensitization, Immunologic ; Heart Transplantation
    Chemical Substances Antibodies, Monoclonal ; daratumumab (4Z63YK6E0E)
    Language English
    Publishing date 2023-09-25
    Publishing country United States
    Document type Case Reports ; Letter
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000004719
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  3. Article ; Online: Effect of donor

    Kozlitina, Julia / Cohen, Naomi M / Sturtevant, Drew / Cohen, Jonathan C / Murphey-Half, Cathi / Saltarrelli, Jerome G / Jindra, Peter / Askar, Medhat / Hwang, Christine S / Vagefi, Parsia A / Lacelle, Chantale / Hobbs, Helen H / MacConmara, Malcolm P

    EClinicalMedicine

    2023  Volume 67, Page(s) 102350

    Abstract: Background: Several genetic variants are associated with chronic liver disease. The role of these variants in outcomes after liver transplantation (LT) is uncertain. The aim of this study was to determine if donor genotype at risk-associated variants in ...

    Abstract Background: Several genetic variants are associated with chronic liver disease. The role of these variants in outcomes after liver transplantation (LT) is uncertain. The aim of this study was to determine if donor genotype at risk-associated variants in
    Methods: In this retrospective cohort study, data on 2346 adults who underwent first-time LT between January 1, 1999 and June 30, 2020 and who had donor DNA samples available at five large Transplant Immunology Laboratories in Texas, USA, were obtained from the United Network for Organ Sharing (UNOS). Duplicates, patients with insufficient donor DNA for genotyping, those who were <18 years of age at the time of transplant, had had a previous transplant or had missing genotype data were excluded. The primary outcomes were patient and graft survival after LT. The association between donor genotype and post-LT survival was examined using Kaplan-Meier method and multivariable-adjusted Cox proportional hazards models.
    Findings: Median age of LT recipients was 57 [interquartile range (IQR), 50-62] years; 837 (35.7%) were women; 1362 (58.1%) White, 713 (30.4%) Hispanic, 182 (7.8%) Black/African-American. Median follow-up time was 3.95 years. Post-LT survival was not affected by donor
    Interpretation: Donor
    Funding: The National Institutes of Health and American Society of Transplant Surgeons Collaborative Scientist Grant.
    Language English
    Publishing date 2023-12-13
    Publishing country England
    Document type Journal Article
    ISSN 2589-5370
    ISSN (online) 2589-5370
    DOI 10.1016/j.eclinm.2023.102350
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  4. Article ; Online: Management of sensitized pediatric patients prior to renal transplantation.

    Pirojsakul, Kwanchai / Desai, Dev / Lacelle, Chantale / Seikaly, Mouin G

    Pediatric nephrology (Berlin, Germany)

    2016  Volume 31, Issue 10, Page(s) 1691–1698

    Abstract: Background: Data on renal allograft outcome in sensitized children are scarce. We report the clinical courses of four children who received desensitization therapy prior to renal transplantation in our institution.: Methods: Between 2009 and 2011, ... ...

    Abstract Background: Data on renal allograft outcome in sensitized children are scarce. We report the clinical courses of four children who received desensitization therapy prior to renal transplantation in our institution.
    Methods: Between 2009 and 2011, four pediatric patients with stage 5 chronic kidney disease received desensitization therapy due to: (1) positive donor-specific antibodies (DSA) and/or crossmatches with potential living donors, (2) more than three positive crossmatches with deceased donors or (3) high calculated panel-reactive antibody of >80 %. Desensitization with rituximab, intravenous immunoglobulin and bortezomib was performed in all patients. Induction therapy included combinations of plasmapheresis and/or alemtuzumab or anti-thymocyte globulin. Standard post-transplant medications included tacrolimus, mycophenolate mofetil and prednisolone.
    Results: Post-transplant screening revealed DSA in three patients. Biopsy showed no evidence of rejection at 1 month in two patients, one of whom developed chronic active antibody-mediated rejection 4.5 years later. One patient developed borderline acute cellular rejection at 1 month, but the serum creatinine level was stable and DSA disappeared without treatment 1 month later, with stable long-term allograft function at 3 years. Estimated or measured glomerular filtration rate of the patients ranged between 30 and 75 ml/min/1.73 m(2) after 1 to 4.5 years.
    Conclusions: The four sensitized patients reported here who received desensitization therapy had successful renal transplants with a low risk of immediate post-transplant rejection. Overall, long-term allograft functions and complications from immunosuppression were encouraging.
    Language English
    Publishing date 2016-10
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 631932-4
    ISSN 1432-198X ; 0931-041X
    ISSN (online) 1432-198X
    ISSN 0931-041X
    DOI 10.1007/s00467-015-3295-z
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  5. Article: Serological Response in Lung Transplant Recipients after Two Doses of SARS-CoV-2 mRNA Vaccines.

    Narasimhan, Madhusudhanan / Mahimainathan, Lenin / Clark, Andrew E / Usmani, Amena / Cao, Jing / Araj, Ellen / Torres, Fernando / Sarode, Ravi / Kaza, Vaidehi / Lacelle, Chantale / Muthukumar, Alagarraju

    Vaccines

    2021  Volume 9, Issue 7

    Abstract: Background: Lung-transplant (LT) recipients are at high risk for COVID-19 due to immunosuppression and respiratory tropism of SARS-CoV-2. The information on the effect of COVID-19 mRNA vaccines to elicit immunogenic responses after a two-dose (2D) ... ...

    Abstract Background: Lung-transplant (LT) recipients are at high risk for COVID-19 due to immunosuppression and respiratory tropism of SARS-CoV-2. The information on the effect of COVID-19 mRNA vaccines to elicit immunogenic responses after a two-dose (2D) regimen in LT recipients is sparse. Thus, we assessed the effect of Pfizer-BioNTech and Moderna mRNA vaccines' 2D regimen on anti-spike responses in immunocompromised LT recipients.
    Methods: We utilized serum samples from LT recipients vaccinated for SARS-CoV-2 with 2D of either the Pfizer-BioNTech or Moderna vaccines and 2D-vaccinated naïve (non-transplanted and non-exposed to COVID-19) group. Antibody responses were assessed using the FDA-approved SARS-CoV-2 anti-nucleocapsid protein IgG assay (IgG
    Results: About 25% (18/73) of SARS-CoV-2 uninfected-LT patients generated a positive spike-IgG response following 2D of vaccines, with 36% (9/25) in the Moderna cohort and only 19% (9/48) in the Pfizer cohort. 2D in LT patients elicited a significantly lesser median IgG
    Conclusion: 2D COVID-19 vaccination elicits a dampened serological response in LT patients. Whether assessing other arms of host immunity combined with a higher vaccine dose can better capture and elicit improved immunogenicity in this immunocompromised population warrants investigation.
    Language English
    Publishing date 2021-06-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines9070708
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  6. Article ; Online: Allograft outcomes of treated children with kidney transplant who developed plasma cell-rich acute rejection (PCAR): A single center's experience.

    Alhamoud, Issa / Huang, Rong / Lacelle, Chantale / Burguete, Daniel / Hendricks, Allen R / Torrealba, Jose R / Seikaly, Mouin G

    Pediatric transplantation

    2019  Volume 23, Issue 6, Page(s) e13500

    Abstract: Introduction: PCAR is a rare form of ACR that may compromise renal allografts. This review evaluates the outcomes of a protocol used to treat PCAR (Study group), and compares these outcomes with a matched cohort with ACR (Control group).: Methods: A ... ...

    Abstract Introduction: PCAR is a rare form of ACR that may compromise renal allografts. This review evaluates the outcomes of a protocol used to treat PCAR (Study group), and compares these outcomes with a matched cohort with ACR (Control group).
    Methods: A retrospective analysis of 138 of pRTRs who underwent renal allograft biopsies between January 2008 and November 2016.
    Results: Seven biopsies revealed in situ hybridization of EBER-negative PCAR (5%). Three Study group pRTRs lost their grafts within 3 months after rejection (43%). None of the Control group pRTRs lost their graft during this period. At the time of rejection, eGFR was different between the Control and Study groups (27.0 ± 19.9 mL/min per m
    Summary: (a) Graft loss in Study group while remaining high (43%) was lower than that reported in the published pediatric literature. (b) Our protocol was associated with improvement in eGFR in all surviving pRTRs within the Study group. (c) No life-threatening complications or malignancy were reported during the observation period.
    MeSH term(s) Adolescent ; Allografts ; B-Lymphocytes/cytology ; Biopsy ; Child ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Graft Rejection/immunology ; Graft Survival ; Humans ; Hypotension ; Immunosuppressive Agents/therapeutic use ; Kidney Transplantation ; Male ; Plasma Cells/cytology ; Retrospective Studies ; Transplantation, Homologous ; Treatment Outcome
    Chemical Substances Immunosuppressive Agents
    Language English
    Publishing date 2019-08-28
    Publishing country Denmark
    Document type Journal Article
    ZDB-ID 1390284-2
    ISSN 1399-3046 ; 1397-3142
    ISSN (online) 1399-3046
    ISSN 1397-3142
    DOI 10.1111/petr.13500
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  7. Article ; Online: Complement (C1q) Binding De Novo Donor-Specific Antibodies and Cardiac-Allograft Vasculopathy in Pediatric Heart Transplant Recipients.

    Das, Bibhuti B / Lacelle, Chantale / Zhang, Song / Gao, Ang / Fixler, David

    Transplantation

    2017  Volume 102, Issue 3, Page(s) 502–509

    Abstract: Background: We hypothesized C1q binding de novo donor-specific antibody (DSA) after heart transplant (HT) is a higher risk for development of coronary artery vasculopathy (CAV) in children.: Methods: A retrospective analysis of 127 pediatric HT ... ...

    Abstract Background: We hypothesized C1q binding de novo donor-specific antibody (DSA) after heart transplant (HT) is a higher risk for development of coronary artery vasculopathy (CAV) in children.
    Methods: A retrospective analysis of 127 pediatric HT recipients transplanted between January 2005 and December 2014 was used to determine complement (C1q)-binding de novo DSA on the outcomes of HT and the ability of the C1q assay to predict CAV development.
    Results: Of 127 patients, 59 (46.4%) developed de novo DSA, 37 of those had C1q+ DSA. There was no difference in baseline characteristics except patients who developed C1q+ DSA more often received a donor heart from a female compared with C1q- DSA group (P = 0.034). The DSA median fluorescent intensity (MFI) value of 7000 or greater had 80% sensitivity and 80% specificity (C statistics 0.89, P <0.05) for predicting positive C1q binding. Multivariate analyses identified C1q binding DSA as an independent risk for CAV with a hazard ratio (HR) of 3.25 (95% confidence interval [CI], 1.33-7.93; P = 0.0095). In multivariable Cox proportional hazard models, the covariates associated with graft loss included: C1q+ DSA (HR, 3.2; 95% CI, 1.34-7.86; P < 0.009), pre-HT renal insufficiency (HR, 11.3; 95% CI, 3.71-34.29; P < 0.0001), and pre-HT ventilator support (HR, 3.3; 95% CI, 1.39-7.81; P = 0.007).
    Conclusions: The DSA strength in MFI correlates with positive C1q-binding activity and hence functional capabilities of DSA. Close monitoring of DSA strength in MFI and function (C1q assay) may be useful for identifying pediatric HT recipient at risk for development of CAV.
    MeSH term(s) Allografts ; Child ; Child, Preschool ; Complement C1q/analysis ; Complement C1q/immunology ; Female ; Graft Rejection ; Heart Transplantation/adverse effects ; Humans ; Infant ; Isoantibodies/immunology ; Male ; Retrospective Studies ; Tissue Donors ; Vascular Diseases/etiology
    Chemical Substances Isoantibodies ; Complement C1q (80295-33-6)
    Language English
    Publishing date 2017-03-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000001944
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  8. Article ; Online: Alemtuzumab (Campath-1H) therapy for refractory rejections in pediatric heart transplant recipients.

    Das, Bibhuti / Dimas, Vivian / Guleserian, Kristine / Lacelle, Chantale / Anton, Kristin / Moore, Lindy / Morrow, Robert

    Pediatric transplantation

    2017  Volume 21, Issue 1

    Abstract: Despite substantial improvements in survival after pediatric heart transplantation, refractory rejection remains a major cause of morbidity and mortality. We have utilized ALE (Campath-1H) in six consecutive patients with refractory rejection. These ... ...

    Abstract Despite substantial improvements in survival after pediatric heart transplantation, refractory rejection remains a major cause of morbidity and mortality. We have utilized ALE (Campath-1H) in six consecutive patients with refractory rejection. These rejection episodes persisted despite conventional treatment, which included intravenous methylprednisolone, rituximab, immunoglobulin G, and antithymocyte globulin. In our series, after ALE therapy, LV SF increased from 22%±5% to 33%±5% (P=.01). However, in our series, ALE therapy neither led to persistent LV function recovery nor could it prevent subsequent antibody-mediated rejection.
    MeSH term(s) Adolescent ; Alemtuzumab ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antilymphocyte Serum/administration & dosage ; Child ; Child, Preschool ; Female ; Graft Rejection/prevention & control ; Heart Transplantation ; Humans ; Immunoglobulin G/administration & dosage ; Infant ; Infusions, Intravenous ; Male ; Methylprednisolone/administration & dosage ; Mycophenolic Acid/administration & dosage ; Prednisone/administration & dosage ; Recombinant Fusion Proteins/administration & dosage ; Retrospective Studies ; Rituximab/administration & dosage ; Tacrolimus/administration & dosage ; Transplant Recipients
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antilymphocyte Serum ; Immunoglobulin G ; Recombinant Fusion Proteins ; Alemtuzumab (3A189DH42V) ; Rituximab (4F4X42SYQ6) ; basiliximab (9927MT646M) ; Mycophenolic Acid (HU9DX48N0T) ; Prednisone (VB0R961HZT) ; Tacrolimus (WM0HAQ4WNM) ; Methylprednisolone (X4W7ZR7023)
    Language English
    Publishing date 2017-02
    Publishing country Denmark
    Document type Journal Article
    ZDB-ID 1390284-2
    ISSN 1399-3046 ; 1397-3142
    ISSN (online) 1399-3046
    ISSN 1397-3142
    DOI 10.1111/petr.12844
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  9. Article ; Online: SARS-CoV-2 Antibody Responses Do Not Predict COVID-19 Disease Severity.

    Phipps, William S / SoRelle, Jeffrey A / Li, Quan-Zhen / Mahimainathan, Lenin / Araj, Ellen / Markantonis, John / Lacelle, Chantale / Balani, Jyoti / Parikh, Hiren / Solow, E Blair / Karp, David R / Sarode, Ravi / Muthukumar, Alagarraju

    American journal of clinical pathology

    2020  Volume 154, Issue 4, Page(s) 459–465

    Abstract: Objectives: Initial reports indicate adequate performance of some serology-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assays. However, additional studies are required to facilitate interpretation of results, including how ... ...

    Abstract Objectives: Initial reports indicate adequate performance of some serology-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assays. However, additional studies are required to facilitate interpretation of results, including how antibody levels impact immunity and disease course.
    Methods: A total of 967 subjects were tested for IgG antibodies reactive to SARS-CoV-2, including 172 suspected cases of SARS-CoV-2, 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for polymerase chain reaction (PCR)-based respiratory viral panel. A subgroup of SARS-CoV-2 PCR-positive cases was tested for IgM antibodies by proteome array method.
    Results: All specificity and cross-reactivity specimens were negative for SARS-CoV-2 IgG antibodies (0/795, 0%). Positive agreement of IgG with PCR was 83% of samples confirmed to be more than 14 days from symptom onset, with less than 100% sensitivity attributable to a case with severe immunosuppression. Virus-specific IgM was positive in a higher proportion of cases less than 3 days from symptom onset. No association was observed between mild and severe disease course with respect to IgG and IgM levels.
    Conclusions: The studied SARS-CoV-2 IgG assay had 100% specificity and no adverse cross-reactivity. Measures of IgG and IgM antibodies did not predict disease severity in our patient population.
    MeSH term(s) Antibodies, Viral/blood ; Antibody Formation ; Betacoronavirus/immunology ; Biomarkers/blood ; COVID-19 ; COVID-19 Testing ; Case-Control Studies ; Clinical Laboratory Techniques ; Coronavirus Infections/blood ; Coronavirus Infections/diagnosis ; Coronavirus Infections/immunology ; Cross Reactions ; Cross-Sectional Studies ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Pandemics ; Pneumonia, Viral/blood ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/immunology ; SARS-CoV-2 ; Sensitivity and Specificity ; Severity of Illness Index
    Chemical Substances Antibodies, Viral ; Biomarkers ; Immunoglobulin G ; Immunoglobulin M
    Keywords covid19
    Language English
    Publishing date 2020-07-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2944-0
    ISSN 1943-7722 ; 0002-9173
    ISSN (online) 1943-7722
    ISSN 0002-9173
    DOI 10.1093/ajcp/aqaa123
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  10. Article ; Online: Donor-specific HLA alloantibodies: Impact on cardiac allograft vasculopathy, rejection, and survival after pediatric heart transplantation.

    Tran, Andrew / Fixler, David / Huang, Rong / Meza, Tiffany / Lacelle, Chantale / Das, Bibhuti B

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

    2015  Volume 35, Issue 1, Page(s) 87–91

    Abstract: Background: There is increasing evidence that donor-specific anti-HLA antibodies (DSA) are associated with poor outcomes after cardiac transplantation in adults, but data are limited in children. The objective of this study was to examine the ... ...

    Abstract Background: There is increasing evidence that donor-specific anti-HLA antibodies (DSA) are associated with poor outcomes after cardiac transplantation in adults, but data are limited in children. The objective of this study was to examine the development and consequences of de novo DSA in pediatric recipients of heart transplants.
    Methods: We analyzed 105 pediatric patients who received heart transplants at our center from January 2002 to December 2012. All patients had negative T-cell and B-cell post-transplant crossmatches. Patients underwent HLA antibody screening at 1, 2, 3, 6, and 12 months post-transplant and annually thereafter unless there was suspicion for rejection. HLA class I and II antibodies were identified using Luminex assay. Coronary angiography was performed at 1 year and annually thereafter. Acute cellular rejection, antibody-mediated rejection, and treated clinical rejections were included together as rejection events.
    Results: Of 105 patients, 45 (43%) developed de novo DSA. DSA-positive patients had significantly higher rates of coronary artery vasculopathy (CAV) compared with DSA-negative patients (36% vs 13%). CAV-free survival at 1 year and 5 years post-transplant for DSA-negative patients was 90% and 25%, respectively, compared with 70% and 0%, respectively, for DSA-positive patients (p < 0.01). DSA-positive patients had 2.5 times more rejection events per year than DSA-negative patients. The 5-year graft survival rate was 72.4% for DSA-negative patients and 21% for DSA-positive patients (p < 0.001).
    Conclusions: De novo DSA has a strong negative impact on CAV, rejection, and graft survival in pediatric recipients of heart transplants.
    MeSH term(s) Adolescent ; Allografts ; B-Lymphocytes/immunology ; Child ; Child, Preschool ; Coronary Artery Disease/immunology ; Coronary Artery Disease/mortality ; Coronary Artery Disease/pathology ; Female ; Follow-Up Studies ; Graft Rejection/immunology ; Graft Rejection/mortality ; Graft Rejection/pathology ; Graft Survival ; HLA Antigens/immunology ; Heart Transplantation/mortality ; Histocompatibility Testing ; Humans ; Infant ; Isoantibodies/immunology ; Male ; Retrospective Studies ; Survival Rate/trends ; Texas/epidemiology ; Time Factors ; Tissue Donors
    Chemical Substances HLA Antigens ; Isoantibodies
    Language English
    Publishing date 2015-09-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1062522-7
    ISSN 1557-3117 ; 1053-2498
    ISSN (online) 1557-3117
    ISSN 1053-2498
    DOI 10.1016/j.healun.2015.08.008
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