THE ROLE OF FLOW CYTOMETRY-DETECTED IgG AND IgM ANTI-DONOR ANTIBODIES IN CARDIAC ALLOGRAFT RECIPIENTS1

Przybylowski, P.; Balogna, M; Radovancĕvíc, B; Frazier, O. H.; Süßkind, B.; Buren, C. Van; Katz, Sanford; Kahan, Barry D.; Kerman, Ronald H.

doi:10.1097/00007890-199901270-00012

Cited by 45 publications

(6 citation statements)

References 11 publications

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“…Heart recipients transplanted in the presence of donor-specific anti- HLA antibodies have a lower graft survival (34, 35) suggesting a possible role for the humoral arm of the immune system in the pathogenesis of CAV. The mechanism may be related to the fact that endothelial cells express both HLA I and II molecules in the context of organ transplantation endowing them with the capacity to present antigen to the recipient T cells but also to be a target for allo-immune responses from donor specific antibodies towards both HLA I and HLA II antigens (36, 37).…”

Section: Discussionmentioning

confidence: 99%

Combined Heart and Liver Transplant Attenuates Cardiac Allograft Vasculopathy Compared with Isolated Heart Transplantation

et al. 2013

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Background We evaluated whether combined heart liver transplant can protect the heart graft from the development of Cardiac allograft vasculopathy (CAV) using coronary 3D volumetric IVUS. Methods From 2004 to 2009, we identified 24 isolated heart transplant (HTx) and 10 combined heart liver transplant (H+Liver Tx) recipients in whom two coronary 3D IVUS studies were performed one year apart. Baseline 3D IVUS was performed at 0.22 [0.17, 1.16] years after transplant with follow up 3D IVUS exams performed 0.96 [0.83, 1.08] after baseline exam. Results Rate of plaque volume and plaque index (plaque volume/vessel volume) progression was attenuated in the H+Liver Tx group (0.3±1.1 mm3/mm vs. 1.5±2.9 mm3/mm; P=0.08, and 0.01±0.03 vs. 0.1±0.1; P=0.004 respectively). Rejection burden was much lower in the H+Liver Tx patients. Outcome analysis in 66 consecutive patients (56 HTx and 10 H+Liver Tx) was performed irrespective of performance of second coronary IVUS. Combined heart and liver transplant was associated with reduced rate of cardiac events (p=0.04), which remained significant when adjusted for the difference in the primary etiology for heart disease (p=0.05). Conclusions Our preliminary serial 3D coronary IVUS data show that combined heart and liver transplant attenuates CAV by decreasing the rate of plaque volume and plaque index progression and improves coronary related outcomes. Because of the small numbers and the differences in etiology of heart disease our data should be interpreted cautiously, and larger clinical trials would be required to recommend combined heart liver transplant for improved coronary remodeling.

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Section: Discussionmentioning

confidence: 99%

Combined Heart and Liver Transplant Attenuates Cardiac Allograft Vasculopathy Compared with Isolated Heart Transplantation

et al. 2013

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“…Hence, at body temperature, they are particularly suited to modulate cell receptors without damaging the cell (4, 6–8). Observations showing that patients with high levels of IgM-ALA have (i) significantly less rejections and prolonged kidney and heart survival (9–13) and (ii) have significantly lower titers of anti-HLA antibodies after alloantigen sensitization (8), support such a concept i.e. that IgM-ALA can regulate immune cells that mediate both innate and adaptive immune inflammatory responses.…”

Section: Introductionmentioning

confidence: 95%

Natural IgM Switches the Function of Lipopolysaccharide-Activated Murine Bone Marrow–Derived Dendritic Cells to a Regulatory Dendritic Cell That Suppresses Innate Inflammation

Lobo

Schlegel

Bajwa

et al. 2015

The Journal of Immunology

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We have previously shown that polyclonal natural IgM protects mice from renal IRI by inhibiting the reperfusion inflammatory response. We hypothesized that a potential mechanism involved IgM modulation of dendritic cells as we observed high IgM binding to splenic DC. To test this hypothesis, we pre-treated BMDC with polyclonal murine or human IgM prior to LPS activation and demonstrate that 0.5 × 106 IgM/LPS pretreated BMDC, when injected into WT-B6 mice, 24 hours before renal ischemia, protect mice from developing renal IRI. We show that this switching of LPS activated BMDC to a regulatory phenotype requires modulation of BMDC function that is mediated by IgM binding to non-apoptotic BMDC receptors. Regulatory BMDC require IL-10 and PD1 as well as downregulation of CD40 and p65NF-κB phosphorylation to protect in renal IRI. Blocking the PD1 ligand binding site just before intravenous injection of IgM/LPS pretreated BMDC or using IL-10ko BMDC fails to induce protection. Similarly, IgM/LPS pretreated BMDC are rendered non-protective by increasing CD40 expression and phosphorylation of p65NF-κB. How IgM/LPS regulatory BMDC suppress in-vivo ischemia induced innate inflammation remains to be determined. However, we show that suppression is dependent on other in-vivo regulatory mechanisms in the host i.e. CD25+ T cells, B cells, IL10 and circulating IgM. There was no increase in Foxp3+ Tregs in the spleen either before or after renal IRI. Collectively, these findings show that natural IgM anti-leucocyte antibodies can switch BMDC to a regulatory phenotype despite the presence of LPS that ordinarily induces BMDC maturation.

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“…Previous studies have shown that HTX recipients who have anti-HLA donor-specific antibodies (DSA) are at increased risk for early acute rejection and have a lower graft survival (2, 3). Newly introduced solid-phase array techniques can distinguish between HLA type and Class I and II antibodies.…”

Section: Introductionmentioning

confidence: 99%

Donor-Specific Antibodies to Class II Antigens Are Associated With Accelerated Cardiac Allograft Vasculopathy

Topilsky

Gandhi

Hasin

et al. 2013

Transplantation Journal

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Background Although a link between donor-specific antibodies against human leukocyte antigens type II (DSA II+) and transplant glomerulopathy has been clearly established, its role in cardiac allograft vasculopathy (CAV) is unclear. Methods DSA were evaluated using solid phase Single Antigen Bead assay before transplant in 51 heart transplant (HTX) recipients. Coronary angiography and three-dimensional intravascular ultrasound (3D IVUS) were performed at baseline and approximately one year after the baseline exam. Results There were 4 (7.8 %), 11 (21.5%), and 2 (3.9%) patients who had DSA against donor Class I (DSA I+), DSA II+, or both respectively. All patients had negative complement dependent cytotoxic cross match. There was accelerated progression of CAV in the DSA II+ group demonstrated by accelerated progression in plaque index (plaque volume/vessel volume) compared to patients with no DSA II+ antibodies (13.8±12% vs. −7.9±37%; p=0.01). The development of any angiographic CAV was also more common in DSA II+ patients as compared to the DSA− patients at 4 years (100±0% vs. 64.2±10%; p=0.05). All other traditional risk factors for CAV, or immunosuppression were similar between the groups (P>0.2 for all). Conclusions This is the first preliminary study demonstrating that HTX recipients with preformed Class II DSA may be at an increased risk for accelerated CAV as detected by consecutive volumetric 3D IVUS.

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THE ROLE OF FLOW CYTOMETRY-DETECTED IgG AND IgM ANTI-DONOR ANTIBODIES IN CARDIAC ALLOGRAFT RECIPIENTS1

Abstract: These data suggest that IgG(+) FCXM identifies a subset of AHG-IgG-NEG XM cardiac allograft recipients who are at risk for early rejections and poor survival. In contrast, the presence of IgM may be beneficial to survival.

Cited by 45 publications

References 11 publications

Combined Heart and Liver Transplant Attenuates Cardiac Allograft Vasculopathy Compared with Isolated Heart Transplantation

Combined Heart and Liver Transplant Attenuates Cardiac Allograft Vasculopathy Compared with Isolated Heart Transplantation

Natural IgM Switches the Function of Lipopolysaccharide-Activated Murine Bone Marrow–Derived Dendritic Cells to a Regulatory Dendritic Cell That Suppresses Innate Inflammation

Donor-Specific Antibodies to Class II Antigens Are Associated With Accelerated Cardiac Allograft Vasculopathy

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