Anti-human leukocyte antigen antibodies, vascular C4d deposition and increased soluble c4d in broncho-alveolar lavage of lung allografts.
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 microg/mL) elevated in patients with HLA-Ab and vascular C4d and was moderately (0.2 microg/mL) increased in patients with antibodies but C4d-negative. In contrast, only a slight elevation of soluble C4d (<0.1 microg/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.
Girnita
Alin L
AL
Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA. girnitaal@upmc.edu
Lee
Teresa M
TM
McCurry
Kenneth R
KR
Baldwin
William M
WM
Yousem
Samuel A
SA
Detrick
Barbara
B
Pilewski
Joseph
J
Toyoda
Yoshiya
Y
Jelinek
Larry
L
Lomago
Jon
J
Zaldonis
Diana
D
Spichty
Kathy J
KJ
Zeevi
Adriana
A
D000328:Adult; D000368:Aged; D001706:Biopsy; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid; D015935:Complement C4b / Q000737:chemistry*; D005260:Female; D006084:Graft Rejection; D006680:HLA Antigens / Q000737:chemistry*; D006801:Humans; D007518:Isoantibodies / Q000737:chemistry; D008168:Lung / Q000473:pathology; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry*
D006680:HLA Antigens; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d