Serological Characterization of Antibodies Eluted From Chronically Rejected Human Renal Allografts

Mohanakumar, T; Jc, Waldrep; Phibbs, M; Méndez-Picón, G; Am, Kaplan; Hm, Lee

doi:10.1097/00007890-198107000-00013

Cited by 51 publications

(21 citation statements)

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“…The tissue fixed/bound antibody would then clearly not be available for serologic detection. Supportive of this potential mechanism are two studies in which eluates of renal allografted tissue contained immunoglobulin and fractions of complement (21,22). We were unable to find additional human studies to support this hypothesis as a potential mechanism.…”

Section: Discussionmentioning

confidence: 82%

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

Magro¹,

Klinger²,

Adams³

et al. 2003

American Journal of Transplantation

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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.

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Section: Discussionmentioning

confidence: 82%

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

Magro¹,

Klinger²,

Adams³

et al. 2003

American Journal of Transplantation

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“…We suggest that these assays will be useful in future studies of alloantibody production in sensitized subjects including: (i) the lifespan and turnover rate of ASCs in vivo; (ii) the contribution of long-lived and short-lived ASCs to alloantibody production at various phases of transplantation; (iii) the mechanism(s) of the 'loss' of donor-specific alloantibody late after transplantation (35,36); (iv) the possibility that donor-specific alloantibody is absorbed by the allograft (37,38); and (v) further tests of efficacy of therapeutic agents on ASC function and antibody production both in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 99%

Two Novel Assays of Alloantibody-Secreting Cells Demonstrating Resistance to Desensitization With IVIG and rATG

Perry

Pollinger

Burns

et al. 2008

American Journal of Transplantation

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Donor-specific alloantibody presents a major barrier to the successful transplantation of kidneys and hearts. However, the study of alloantibody production has been hampered by both an inadequate source of antibody-secreting cells (ASCs) and a paucity of assays to determine their function. We describe two new assays that allow for the determination of the frequency and specificities of allo-ASCs in humans using purified HLA as targets. These assays demonstrated allo-ASCs in the CD138 + fraction of the bone marrow, but not in peripheral blood. Alloantibody specificities in these assays correlated well with those detected in the serum suggesting that bone marrow-derived ASCs are indeed a major source of alloantibody in vivo. However, ASCs for a specific HLA antigen were rare with an estimated frequency of only 1/2 × 10 6 marrow cells. Pretransplant treatment in vivo with multiple plasmaphereses and low-dose IVIG alone or in combination with rATG had no effect on ASC number or alloantibody production. These techniques allow for the study of allospecific ASCs and provide a method to test the potential efficacy of agents on alloantibody production in vivo.

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“…The low levels of circulating alloantibody observed in Group 1 and Group 2 recipients (Figure 4), despite evidence of graft rejection, may be explained by absorption of such antibodies in the allograft (32)(33)(34). Lack of in vitro donor responsiveness in recipients at the time when they demonstrated histological signs of rejection (Table III) may have been due to the sequestration of anti-donor, cytotoxic lymphocyte precursors within the rejecting lung allograft.…”

Section: Discussionmentioning

confidence: 97%

Recipient-Matching of Passenger Leukocytes Prolongs Survival of Donor Lung Allografts in Miniature Swine.

et al. 2014

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Serological Characterization of Antibodies Eluted From Chronically Rejected Human Renal Allografts

Cited by 51 publications

References 0 publications

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

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

Two Novel Assays of Alloantibody-Secreting Cells Demonstrating Resistance to Desensitization With IVIG and rATG

Recipient-Matching of Passenger Leukocytes Prolongs Survival of Donor Lung Allografts in Miniature Swine.

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