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

Przybyłowski, Piotr; Bologna, Marco Alberto; Radovančević, Branislav; Frazier, O.H.; Süßkind, B.; Buren, C. Van; Katz, Stephen I.; Kahan, Barry D.; Kerman, Ronald H.

doi:10.1097/00007890-199810270-00092

Cited by 13 publications

(16 citation statements)

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“…These data, together with previously published data, would indicate that IgM-ALA may have a role in inhibiting or attenuating the inflammatory response mediated by acute rejections (27)(28)(29)(30)(31). Presence of high IgM-ALA did not corelate with age, sex, race, renal disease causing ESRD or pretransplant exposure to CMV and EBV viruses.…”

Section: High Igm-ala Levels Are Associated With Minimal Acute Rejectsupporting

confidence: 73%

“…However clues on the potential identity of some of these receptors became apparent when we attempted to explain certain clinical observations in human kidney and heart transplants. Allograft recipients with high levels of IgM-ALA were found to have significantly better allograft survival and fewer rejections even during the precyclosporin era (27)(28)(29)(30)(31). Recognizing that rejection in an allograft is a T cell mediated inflammatory process, we hypothesized that IgM-ALA mediated these inhibitory effects by binding to leukocyte receptors involved in T cell activation and leukocyte chemotaxis.…”

Section: Discussionmentioning

confidence: 99%

“…Human kidney and heart transplants performed in the subset (approx. 30%) of patients having high levels of IgM-ALA have a lower incidence of acute rejections and of less severity, thus permitting better graft survival (27)(28)(29)(30)(31). The protective effect of IgM-ALA in allograft transplantation together with the observation that IgM-ALA nonspecifically increase in various inflammatory and infective states led us to hypothesize whether the increased production of IgM-ALA has a role in inhibiting T cell activation and attenuating the inflammatory response by binding to certain cell membrane receptors important in the inflammatory process i.e., receptors that activate T lymphocytes and receptors that are important for chemotaxis.…”

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confidence: 99%

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Naturally Occurring IgM Anti-Leukocyte Autoantibodies (IgM-ALA) Inhibit T Cell Activation and Chemotaxis

Lobo¹,

Schlegel²,

Spencer³

et al. 2008

The Journal of Immunology

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The physiological relevance of naturally occurring IgM-ALA remains to be elucidated. These autoantibodies are present from birth and increase in diverse inflammatory states that are both infectious and noninfectious. Clinical observations showing significantly less acute allograft rejections in recipients having high IgM-ALA levels, led us to investigate whether IgM-ALA could have a functional role in attenuating T cell mediated inflammatory responses. In pursuit of this hypothesis, we did studies using IgM purified from the serum of normal individuals, patients with end stage renal disease, and HIV-1 infection. All preparations of IgM immunoprecipitated certain receptors e.g., CD3, CD4, CCR5, and CXCR4 from whole cell lysates but failed to immunoprecipitate IL-2R and HLA Ags. In physiological doses IgM down-regulated CD4, CD2 and CD86 but not CD8 and CD28, inhibited T cell proliferation, decreased production of certain proinflammatory cytokines e.g., TNF-α, IL-13 and IL-2, but not IFN- γ, IL-1β, GM-CSF, IL-6 and IL-8 and inhibited leukocyte chemotaxis. These inhibitory effects were more pronounced when using IgM from patients with high levels of IgM-ALA and these inhibitory effects were significantly reduced after using IgM preabsorbed with leukocytes. IgM-ALA binding to leukocytes was found to be highly specific, as <10% of IgM secreting B cell clones had IgM-ALA specificity with some clones having specificity for either T cells or monocytes. These findings support the concept that IgM-ALA provides an innate mechanism to regulate T cell mediated inflammatory responses.

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Section: High Igm-ala Levels Are Associated With Minimal Acute Rejectsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Naturally Occurring IgM Anti-Leukocyte Autoantibodies (IgM-ALA) Inhibit T Cell Activation and Chemotaxis

Lobo¹,

Schlegel²,

Spencer³

et al. 2008

The Journal of Immunology

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“…Alloantibodies in the clinical setting are strongly correlated with the occurrence of hyperacute, acute Ab-mediated, Ab-mediated cellular and chronic rejection (8)(9)(10)(11). The importance of Abs, upstream of complement activation, in precipitating acute rejection was suggested by Wasowska et al (12) in an experimental model with B cell-deficient recipients that exhibited delayed rejection of allogeneic hearts.…”

mentioning

confidence: 99%

Alloantibodies Prevent the Induction of Transplantation Tolerance by Enhancing Alloreactive T Cell Priming

Burns

Chong

2011

The Journal of Immunology

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Circulating alloantibodies in transplant recipients are often associated with increased Ab-mediated as well as cellular rejection. We tested the hypothesis that alloantibodies facilitate cellular rejection by functioning as opsonins to enhance T cell activation using a BALB/c to C57BL/6 heart or skin transplant model. Long-term heart and skin survival induced with anti-CD154 alone or in combination with donor-specific transfusion (DST), respectively, was abrogated by the presence of anti-Kd mAbs, and alloreactive T cell activation as well as acute rejection was observed. The prevention of graft acceptance in the skin model was dependent on anti-Kd binding to and converting DST from tolerigenic to immunogenic. Adoptive transfer of CFSE-labeled TCR-transgenic T cells into B6 recipients treated with anti-CD154/DST revealed the ability of anti-Kd to enhance the proliferation of anti–Kd-specific T cells via the indirect pathway as well as of non–Kd-reactive, recipient MHC-restricted CD4+ and CD8+ T cells. Thus, alloantibodies with restricted specificity are able to facilitate the indirect presentation as well as the cross-presentation of a larger repertoire of “linked” donor-derived Ags. These observations highlight the ability of alloantibodies to function not only in classical humoral rejection but also as opsonins that facilitate the CD40-CD154–independent activation of alloreactive T cells.

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“…Thus, use of flow cytometry to detect donor-specific crossmatch before cardiac transplantation predicted which patient would have more acute rejection episodes after the operation. 11 All patients in that study had been transplanted against a negative crossmatch using the conventional complement-dependent method.…”

Section: Detection Of Circulating Antibodiesmentioning

confidence: 99%

De novo production of antibodies after heart or lung transplantation should be regarded as an early warning system

Rose

2004

The Journal of Heart and Lung Transplantation

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

Cited by 13 publications

References 0 publications

Naturally Occurring IgM Anti-Leukocyte Autoantibodies (IgM-ALA) Inhibit T Cell Activation and Chemotaxis

Naturally Occurring IgM Anti-Leukocyte Autoantibodies (IgM-ALA) Inhibit T Cell Activation and Chemotaxis

Alloantibodies Prevent the Induction of Transplantation Tolerance by Enhancing Alloreactive T Cell Priming

De novo production of antibodies after heart or lung transplantation should be regarded as an early warning system

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