Use of C4d as a Diagnostic Adjunct in Lung Allograft Biopsies

We describe the decline in islet function, in relation to HLA sensitization, in an islet transplant recipient and the recovery of this function after treatment with anti-CD20 monoclonal antibody and IV immunoglobulins. A 51-year-old woman with type 1 diabetes received one intraportal islet infusion. Following this transplantation, she became insulin independent. A search for HLA antibodies by using an ELISA technique remained consistently negative for HLA class I and II. It was only 2 years after the islet transplantation that this search became positive against class II antigens, reaching a peak of reactivity concomitantly with the appearance of a deterioration of glucose control requiring low-dose insulin therapy. Luminex R screening and single-antigen assays then revealed the presence of both nondonor-specific and donor-specific antibodies against HLA class II molecules. This immunization, already present in the pretransplant serum, had increased during the 6 months preceding the clinical deterioration. Since these data nevertheless pointed to antibody-mediated rejection of the islet allograft, treatment with anti-CD20 monoclonal antibody and IV immunoglobulins was initiated. One month later, the search by ELISA for antibodies against HLA class II antigens became negative, the Luminex R tests normalizing more gradually. As the result of an improvement in glucose control, the patient was again insulin-free.

Section: Discussionmentioning

confidence: 91%

Evidence for Humoral Rejection of a Pancreatic Islet Graft and Rescue with Rituximab and IV Immunoglobulin Therapy

Kessler

Parissiadis

Bayle

et al. 2009

“…C4d immunostaining analysis was also reported in lung transplantation (56). Magro et al evaluated 52 transbronchial biopsies of 23 lung transplant recipients with recurrent acute and chronic rejection.…”

Section: Humoral Rejection In Other Solid Organ Allograftsmentioning

confidence: 99%

Humoral Rejection of Organ Allografts

Moll

Pascual

2005

101

In recent years, the deleterious clinical consequences of recipient de novo alloantibody production against HLA antigens from human organ allografts have been extensively investigated. In kidney transplantation, the identification of the complement C4d fragment in peritubular capillaries as a specific marker for humoral rejection has helped to define and characterize distinct clinical alloantibody-mediated syndromes. This knowledge is relevant for patient management as new therapeutic strategies to remove and control anti-donor antibody production, particularly in the setting of acute humoral rejection, have been reported. For recipients of nonrenal organ allografts such as heart transplant recipients, de novo anti-HLA alloantibody may also be important, although more studies are needed before clear guidelines can be proposed.

“…As further evidence of the role of humoral immunity in the pathogenesis of lung allograft dysfunction is the direct correlation of the degree of C4d deposition with the clinical status of the patient and the degree of parenchymal injury (3). C4d is a stable component of classic complement pathway activation and is held to be a marker of humoral allograft rejection (4,5). Recognizing that humoral allograft rejection in the lung appears to be clinically and pathogenetically significant, the question arises as to the nature of the involved antigenic target.…”

Section: Introductionmentioning

confidence: 99%

Evidence That Humoral Allograft Rejection in Lung Transplant Patients Is Not Histocompatibility Antigen-Related

Magro¹,

Klinger²,

Adams³

et al. 2003

Self Cite

We have recently recognized humoral rejection (HR) in lung allograft recipients and its association with acute and chronic graft dysfunction. We have shown that C4d, a stable marker of classic complement activation, is deposited in lung allografts, correlating with clinical rejection and parenchymal injury. The antigenic target may be endothelium in the setting of recurrent acute rejection while varying components of the bronchial wall may be important in chronic graft dysfunction. We sought to establish whether there is a role for antibodies with histocompatibility antigen specificity in the lung humoral allograft phenomenon. Flow cytometric and ELISA assays to assess donor-specific antigens were conducted on sera from 25 lung transplant recipients who had experienced one or more episodes of clinical rejection; in addition, the serum samples were tested for evidence of antiendothelial cell antibody activity. Morphologically, each case had biopsies showing septal capillary injury with significant deposits of immunoreactants with microvascular localization and positive indirect immunofluorescent antiendothelial cell antibody assay. Panel-reactive antibody testing showed absence of MHC Class I/II alloantibodies; ELISA based crossmatch detecting donor-specific MHC Class I/II specific antibodies was negative. HR can occur in the absence of antibodies with HLA specificity; antigenic targets may be of endothelial cell origin.