Anti-human leukocyte antigen antibodies, vascular C4d deposition and increased soluble C4d in broncho-alveolar lavage of lung allografts

Alin L. Girnita, Teresa M. Lee, Kenneth R. McCurry, William M. Baldwin, Samuel A. Yousem, Barbara Detrick, Joseph Pilewski, Yoshiya Toyoda, Larry Jelinek, Jon Lomago, Diana Zaldonis, Kathy J. Spichty, Adriana Zeevi

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND.: The hallmark of humoral rejection is the presence of subendothelial C4d in the allograft. A simultaneous determination of vascular C4d with soluble C4d in broncho-alveolar lavage fluid (BAL) and circulating anti-human leukocyte antigen (HLA) antibodies (HLA-Ab) has not been reported in lung transplantation. METHODS.: Forty-two consecutive lung-transplant patients were included in this cross-sectional study. The presence and specificity of HLA-Ab was determined at the same frequency with transbronchial biopsies. Soluble C4d levels were measured by enzyme-linked immunosorbent assay in all 42 patients. In a subgroup of 32 patients with available timely matched paraffin-embedded tissue sections, the vascular C4d deposition was also assessed. RESULTS.: The presence of HLA-Ab in 16 patients was associated with biopsy-proven acute rejection (10/16 vs. 3/16, P<0.01) and increased immunosuppression (13/16 vs. 4/16, P<0.005). Pulmonary function was also decreased in patients with HLA-Ab (mean forced expiratory volume in 1 second=49%) when compared with the control group (mean forced expiratory volume in 1 second=66%, P<0.05). Nine patients exhibited specific vascular C4d deposition and in eight of nine (89%) cases HLA-Ab were detected, versus 8 of 23 (35%) in C4d-negative patients (P<0.05). Soluble C4d in BAL was highly (>0.5 μg/mL) elevated in patients with HLA-Ab and vascular C4d and was moderately (0.2 μg/mL) increased in patients with antibodies but C4d-negative. In contrast, only a slight elevation of soluble C4d (<0.1 μg/mL) was detected in patients without HLA-specific antibodies. CONCLUSIONS.: The association of HLA-specific antibodies with vascular C4d deposition and soluble C4d in BAL, in addition to the reduced pulmonary function, might constitute a diagnostic triad for antibody-mediated rejection in lung transplant patients.

Original languageEnglish (US)
Pages (from-to)342-347
Number of pages6
JournalTransplantation
Volume86
Issue number2
DOIs
StatePublished - Jul 27 2008

Keywords

  • Antibodies
  • Complement C4d
  • HLA
  • Lung transplant
  • Rejection

ASJC Scopus subject areas

  • Transplantation

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