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Transplantation
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Complement Activation in Acute Humoral Renal Allograft Rejection

Diagnostic Significance of C4d Deposits in Peritubular Capillaries

A. BERNARD COLLINS, EVELINE E. SCHNEEBERGER, MANUEL A. PASCUAL, SUSAN L. SAIDMAN, WINFRED W. WILLIAMS, NINA TOLKOFF-RUBIN, A. BENEDICT COSIMI and ROBERT B. COLVIN
JASN October 1999, 10 (10) 2208-2214; DOI: https://doi.org/10.1681/ASN.V10102208
A. BERNARD COLLINS
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EVELINE E. SCHNEEBERGER
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MANUEL A. PASCUAL
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SUSAN L. SAIDMAN
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WINFRED W. WILLIAMS
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NINA TOLKOFF-RUBIN
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A. BENEDICT COSIMI
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ROBERT B. COLVIN
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    Figure 1.

    Light micrograph of a renal allograft biopsy with acute humoral rejection, showing accumulation of neutrophils in peritubular capillaries. Periodic acid-Schiff stain. Magnification, ×256.

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    Figure 2.

    Immunofluorescence micrograph of renal allograft biopsies stained for C4d (see Materials and Methods). (A) Acute humoral rejection, with diffuse bright staining for C4d in the peritubular capillaries. (B) Acute cellular rejection, which has C4d in tubular basement membranes, but no detectable deposition of C4d in peritubular capillaries. Magnification, ×200.

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    Figure 3.

    Double immunofluorescence stains of renal allograft biopsies with acute humoral rejection. In the same field, the green filter (A) shows C4d and the red filter (B) type IV collagen codistributed in the peritubular capillaries. The tubular basement membrane stains uniformly for type IV collagen but only focally for C4d. In another pair of fields, the red filter (C) shows C4d in the same distribution as the endothelial marker, Ulex lectin (D, green filter). Portions of vessels show C4d deposits without Ulex lectin reactivity (arrow), suggesting that the C4d remains after loss or injury of the endothelium. Magnification, ×200.

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    Table 1.

    Acute humoral rejection in patents with renal allograftsa

    PatientDonor SourceCirculating Antibodies to DonorBiopsy No.bPTC PMNPTC IgMPTC C3PTC C4dGraft SurvivalbCreatinine (mg/dl) at 1 yr
    T CellsB Cells
    aPTC, peritubular capillaries; PMN, polymorphonuclear leukocytes; ND, not determined; CD, cadaveric kidney. The number after CD indicates the number of renal allografts the patient has received.
    bThe number in parentheses indicates days posttransplantation.
    cPatient was presensitized at time of transplantation.
    dThis patient's original disease was hereditary nephritis. His clinical course was complicated by the presence of anti-glomerular basement membrane antibodies in the kidney.
    eDetermined by flow cytometry.
    fGraft has survived the first 6 wk. Patients 5 through 10 were treated with a rescue protocol combining tacrolimus with mycophenolate and/or plasma exchange (10).
    1CD1:4>1:81 (5)2+--2 to 3+Failed (8)
    2CD>1:8>1:81 (8)3++-4+Survived1.6
    3CD, 3NDND2 (17)2+--1 to 2+Failed (180)
    >1:8>1:83 (33)2+--2+
    4cCD, 21:32Negative1 (6)2+-+3+Failed (23)
    1:16ND2 (12)2+-+/-3+
    5Daughter1:32>1:81 (7)2+--4+Survived
    1:16ND2 (34)3+--4+1.8
    6CD>1:81:42 (26)2+--4+Survived1.2
    7CD1:1281:41 (14)2+-+4+Survived
    >1:5121:642 (21)3+--4+1.1
    8CD, 3Negative>1:81 (7)1 to 2+--4+Survived1.3
    9dCD, 3PositiveePositivee1 (3)3+++4+Failed (10)
    10MotherNegative1:2561 (6)3+++4+Survivedf
    1:21:1282 (17)3+-+3+
    Weak1:163 (24)2 to 3+-+2 to 3+3.1
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    Table 2.

    Other categories of allograft biopsies examineda

    DiagnosisBiopsies ExaminedNo. with AntibodiesNo. with PTCNo. with PTC C4d
    Retrospective testing of this patient's serum revealed circulating anti-class I antibodies.
    aCsA, cyclosporin A; NDAR, no diagnostic abnormality recognized. Other abbreviations as in Table 1.
    bIn one of the six cases with morphologic features of CsA toxicity and without ptc pmn, the ptc stained positively for C4d.
    Acute cellular rejection140 of 84 of 140 of 14
    CsA toxicity61 of 63 of 61 of 6b
    NDAR/donor biopsy40 of 40 of 4
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Journal of the American Society of Nephrology: 10 (10)
Journal of the American Society of Nephrology
Vol. 10, Issue 10
1 Oct 1999
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Complement Activation in Acute Humoral Renal Allograft Rejection
A. BERNARD COLLINS, EVELINE E. SCHNEEBERGER, MANUEL A. PASCUAL, SUSAN L. SAIDMAN, WINFRED W. WILLIAMS, NINA TOLKOFF-RUBIN, A. BENEDICT COSIMI, ROBERT B. COLVIN
JASN Oct 1999, 10 (10) 2208-2214; DOI: 10.1681/ASN.V10102208

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Complement Activation in Acute Humoral Renal Allograft Rejection
A. BERNARD COLLINS, EVELINE E. SCHNEEBERGER, MANUEL A. PASCUAL, SUSAN L. SAIDMAN, WINFRED W. WILLIAMS, NINA TOLKOFF-RUBIN, A. BENEDICT COSIMI, ROBERT B. COLVIN
JASN Oct 1999, 10 (10) 2208-2214; DOI: 10.1681/ASN.V10102208
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More in this TOC Section

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  • Long-Term Benefits with Sirolimus-Based Therapy after Early Cyclosporine Withdrawal
  • Leukocyte Reduction of Red Blood Cell Transfusions Does not Decrease Allosensitization Rates in Potential Kidney Transplant Candidates
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  • Eculizumab to Treat Antibody-Mediated Rejection in a 7-Year-Old Kidney Transplant Recipient
  • Detection of C3d-Binding Donor-Specific Anti-HLA Antibodies at Diagnosis of Humoral Rejection Predicts Renal Graft Loss
  • Thrombotic Microangiopathy and Peritubular Capillary C4d Expression in Renal Allograft Biopsies
  • C4d Deposition without Rejection Correlates with Reduced Early Scarring in ABO-Incompatible Renal Allografts
  • De Novo Production of K-{alpha}1 Tubulin-Specific Antibodies: Role in Chronic Lung Allograft Rejection
  • Anti-MHC Class I Antibody Activation of Proliferation and Survival Signaling in Murine Cardiac Allografts
  • Antibody-Mediated Rejection of Cardiac Allografts in CCR5-Deficient Recipients
  • Inhibition of Terminal Complement Components in Presensitized Transplant Recipients Prevents Antibody-Mediated Rejection Leading to Long-Term Graft Survival and Accommodation
  • Antibody-Mediated Renal Allograft Rejection: Diagnosis and Pathogenesis
  • Mechanisms and Role of HLA and non-HLA Alloantibodies
  • Comparison of C4d Immunostaining Methods in Renal Allograft Biopsies
  • Antibody-Mediated Rejection in Renal Allografts: Lessons from Pathology
  • Hepatitis C, Acute Humoral Rejection, and Renal Allograft Survival
  • Apoptosis and Cellular Activation in the Pathogenesis of Acute Vascular Rejection
  • Membrane Attack Complex Contributes to Destruction of Vascular Integrity in Acute Lung Allograft Rejection
  • Capillary C4d Deposition as a Marker of Humoral Immunity in Renal Allograft Rejection
  • C4d and the Fate of Organ Allografts
  • Capillary Deposition of Complement Split Product C4d in Renal Allografts is Associated with Basement Membrane Injury in Peritubular and Glomerular Capillaries: A Contribution of Humoral Immunity to Chronic Allograft Rejection
  • Capillary C4d Deposition in Kidney Allografts: A Specific Marker of Alloantibody-Dependent Graft Injury
  • Acute Humoral Rejection in Kidney Transplantation: II. Morphology, Immunopathology, and Pathologic Classification
  • Detection of the Complement Degradation Product C4d in Renal Allografts: Diagnostic and Therapeutic Implications
  • C4d Deposition in Acute Rejection: An Independent Long-Term Prognostic Factor
  • C4d-Positive Acute Humoral Renal Allograft Rejection: Effective Treatment by Immunoadsorption
  • Chronic Humoral Rejection: Identification of Antibody-Mediated Chronic Renal Allograft Rejection by C4d Deposits in Peritubular Capillaries
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