Increased erythrocyte C4D is associated with known alloantibody and autoantibody markers of antibody-mediated rejection in human lung transplant recipients

Angali Golocheikine, Dilip S. Nath, Haseeb Ilias Basha, Deepti Saini, Donna Phelan, Aviva Aloush, Elbert P. Trulock, Ramsey R. Hachem, G. Alexander Patterson, Joseph M. Ahearn, Thalachallour Mohanakumar

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Background: Immune responses to mismatched donor human leukocyte antigens (HLA) are important in the pathogenesis of chronic rejection. This study evaluated whether erythrocyte-bound C4d (E-C4d) is associated with known alloimmune and autoimmune markers of antibody-mediated rejection after human lung transplantation (LTx). Methods: Flow cytometry was used to analyze 22 LTx recipients and 15 healthy individuals for E-C4d. Development of antibodies to donor-mismatched HLA (donor-specific antibody [DSA]) and antibodies to HLA were determined using the solid-phase method by Luminex. Development of antibodies to self-antigens, K-α-1-tubulin (KA1T) and collagen V (Col-V), were measured by enzyme-linked immunosorbent assay. C3d deposition in lung biopsy specimens was determined by immunohistochemical staining. Results: Percent E-C4d (%E-C4d) levels were 19.9% in LTx patients vs 3.7% in healthy individuals (p = 0.02). DSA+ patients had higher E-C4d levels than DSA- patients (34.1% vs 16.7%, p = 0.02). In 5 patients with preformed anti-HLA, E-C4d levels were not significantly different vs 13 patients without detectable anti-HLA (p = 0.1). E-C4d levels were higher in patients who developed antibodies to KA1T (p = 0.02) and Col-V (p = 0.03). Recipients with C3d-positive tissue deposition had higher E-C4d levels than patients with C3d-negative biopsy results (p = 0.01). Conclusions: Increased %E-C4d levels are found in patients with positive DSA, high antibody titers to KA1T and Col-V, and have C3d+ lung biopsy findings. Therefore, %E-C4d can serve as a potential marker for antibody-mediated rejection after LTx.

Original languageEnglish
Pages (from-to)410-416
Number of pages7
JournalJournal of Heart and Lung Transplantation
Volume29
Issue number4
DOIs
StatePublished - Apr 1 2010

Keywords

  • AMR
  • complement degradation products
  • erythrocytes
  • lung transplantation
  • self-antigens

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