Pre-transplant donor HLA-specific antibodies: Characteristics causing detrimental effects on survival after lung transplantation

Smith, John D.; Ibrahim, Mohamed W.; Newell, Helen; Danskine, Anna J.; Soresi, Simona; Burke, Margaret; Rose, Marlene L.; Carby, Martin

doi:10.1016/j.healun.2014.02.033

Cited by 80 publications

(64 citation statements)

References 34 publications

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“…32,33 Moreover, mechanisms and strength of antibody production in patients with preformed versus de novo DSA are different. 2,8 In our study, outcomes and DSA clearance did not differ in patients with preformed DSA versus patients with de novo DSA in each group ( Table S1, SDC, http://links.lww.com/TP/B222). In addition, outcomes and DSA clearance among IVIG and tPE patients showed similar results before and after stratification according to presence of preformed versus de novo DSA ( Table S1, SDC, http://links.lww.com/TP/B222 and Table 5 ).…”

Section: Discussionmentioning

confidence: 57%

“…Preoperative patient characteristics were mostly similar among groups (Tables 1 and 2), without any significant difference in the prevalence of preoperative anti-HLA antibodies, which have been demonstrated to be a risk factor for mortality and graft dysfunction elsewhere, 8 but not at our institution. 6 Groups A, B, and C showed a different pattern of cumulative HLA mismatches.…”

Section: Resultsmentioning

confidence: 63%

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IgM-Enriched Human Intravenous Immunoglobulin-Based Treatment of Patients With Early Donor Specific Anti-HLA Antibodies After Lung Transplantation

et al. 2016

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BackgroundAt our institution, until April 2013, patients who showed early donor specific anti-HLA antibodies (DSA) after lung transplantation were preemptively treated with therapeutic plasma exchange (tPE) and a single dose of Rituximab. In April 2013, we moved to a therapy based on IgM-enriched human immunoglobulins (IVIG), repeated every 4 weeks, and a single dose of Rituximab.MethodsThis observational study was designed to evaluate the short-term patient and graft survival in patients who underwent IVIG-based DSA treatment (group A, n = 57) versus contemporary patients transplanted between April 2013 and January 2015 without DSA (group C, n = 180), as well as to evaluate DSA clearance in IVIG-treated patients versus historic patients who had undergone tPE-based treatment (group B, n = 56). Patient records were retrospectively reviewed. Follow-up ended on April 1, 2015.ResultsAt 6 months and 1 year of follow-up, group A had a survival similar to group C (P = 0.81) but better than group B (P = 0.008). Group A showed statistically nonsignificant trends toward improved freedom from pulsed-steroid therapy and biopsy-confirmed rejection over groups B and C. The DSA clearance was better in group A than group B at treatment end (92% vs 64%; P = 0.002) and last DSA control (90% vs 75%; P = 0.04).ConclusionsPatients with new early DSA but without graft dysfunction that are treated with IVIG and Rituximab have similarly good early survival as contemporary lung transplant recipients without early DSA. The IVIG yielded increased DSA clearance compared with historic tPE-based treatment, yet spontaneous clearance of new DSA also remains common.

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Section: Discussionmentioning

confidence: 57%

Section: Resultsmentioning

confidence: 63%

IgM-Enriched Human Intravenous Immunoglobulin-Based Treatment of Patients With Early Donor Specific Anti-HLA Antibodies After Lung Transplantation

et al. 2016

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“…A total of 50 sDSA were found, among which were 14 HLA-DQA1). The median MFI of sDSA was 1804 (IQR 940-3720) for those not found in biopsies, and 10383 (IQR 3707-19237) for those found in biopsies, which was significantly different (gDSA+ vs gDSA-: p=0.003, Figure 1B).…”

Section: Characteristics Of Sdsa and Gdsamentioning

confidence: 99%

“…[7][8][9][10] This was further demonstrated using single antigen flow beads (SAFB) assays which greatly improved the resolution and the sensitivity of donor-specific antibodies (DSA) detection. [11][12][13][14][15][16] However, detection of serum DSA with SAFB has technical limitations, falsenegative and false-positive results being respectively caused by complement interference [17][18][19] and by anti-HLA antibodies of ill-defined pathogenic role recognizing denatured class I HLA molecules. [20][21][22][23][24][25] The presence of DSA is not synonymous with lung allograft injury.…”

Section: Introductionmentioning

confidence: 99%

Lung intragraft donor-specific antibodies as a risk factor for graft loss

Visentin

Chartier

Massara

et al. 2016

The Journal of Heart and Lung Transplantation

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“…Growing evidence supports the notion that the capacity of anti-HLA DSA to bind complement significantly improves our ability to predict ABMR and allograft loss. The clinical relevance of posttransplant complement-binding anti-HLA DSA detected using C1q or C3d assays has been recently shown by several groups in kidney transplantation in the United States and in Europe [18, 20–27] and has also been extended to other solid transplant organs, including heart [19, 30], liver [55], and lung [56]. In the study by Loupy et al [24], posttransplant C1q-binding anti-HLA DSA detected within the first year after transplantation were found to be an independent determinant of allograft loss with a 4.8-fold increased risk.…”

Section: Circulating Donor-specific Anti-hla Antibodies For Risk Smentioning

confidence: 99%

From Humoral Theory to Performant Risk Stratification in Kidney Transplantation

Lefaucheur

Viglietti

Mangiola

et al. 2017

Journal of Immunology Research

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The purpose of the present review is to describe how we improve the model for risk stratification of transplant outcomes in kidney transplantation by incorporating the novel insights of donor-specific anti-HLA antibody (DSA) characteristics. The detection of anti-HLA DSA is widely used for the assessment of pre- and posttransplant risks of rejection and allograft loss; however, not all anti-HLA DSA carry the same risk for transplant outcomes. These antibodies have been shown to cause a wide spectrum of effects on allografts, ranging from the absence of injury to indolent or full-blown acute antibody-mediated rejection. Consequently, the presence of circulating anti-HLA DSA does not provide a sufficient level of accuracy for the risk stratification of allograft outcomes. Enhancing the predictive performance of anti-HLA DSA is currently one of the most pressing unmet needs for facilitating individualized treatment choices that may improve outcomes. Recent advancements in the assessment of anti-HLA DSA properties, including their strength, complement-binding capacity, and IgG subclass composition, significantly improved the risk stratification model to predict allograft injury and failure. Although risk stratification based on anti-HLA DSA properties appears promising, further specific studies that address immunological risk stratification in large and unselected populations are required to define the benefits and cost-effectiveness of such comprehensive assessment prior to clinical implementation.

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Pre-transplant donor HLA-specific antibodies: Characteristics causing detrimental effects on survival after lung transplantation

Cited by 80 publications

References 34 publications

IgM-Enriched Human Intravenous Immunoglobulin-Based Treatment of Patients With Early Donor Specific Anti-HLA Antibodies After Lung Transplantation

IgM-Enriched Human Intravenous Immunoglobulin-Based Treatment of Patients With Early Donor Specific Anti-HLA Antibodies After Lung Transplantation

Lung intragraft donor-specific antibodies as a risk factor for graft loss

From Humoral Theory to Performant Risk Stratification in Kidney Transplantation

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