Acute humoral rejection of human lung allografts and elevation of C4d in bronchoalveolar lavage fluid.
Antibody-mediated rejection is well established for renal allografts but remains controversial for lung allografts. Cardinal features of antibody-mediated rejection in renal allografts include antibodies to donor human leukocyte antigen (HLA) and evidence for antibody action, such as complement activation demonstrated by C4d deposition. We report a lung allograft recipient with circulating antibodies to donor HLA who failed treatment for acute cellular rejection but responded to therapy for humoral rejection. To address the second criteria for antibody-mediated rejection, we determined whether complement activation could be detected by measuring C4d in bronchoalveolar lavage fluid (BALF) by ELISA. Airway allergen challenge of asthmatics activates the complement pathway; therefore, we used BALF from asthmatics pre- and post-allergen challenge to measure C4d. These controls demonstrated that ELISA could detect increases in C4d after allergen challenge. BALF from the index patient had elevated C4d concomitant with graft dysfunction and anti-donor HLA in the absence of infection. Analysis of BALF from 25 additional lung allograft recipients showed that C4d concentrations >100 ng/mL were correlated with anti-HLA antibodies (p = 0.006), but were also observed with infection and in asyptomatic patients. The findings support the occurrence of anti-HLA-mediated lung allograft rejection and suggest that C4d measurement in BALF may be useful in diagnosis.
Miller
Geraldine G
GG
Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. geraldine.miller@vanderbilt.edu
Destarac
Luis
L
Zeevi
Adriana
A
Girnita
Alin
A
McCurry
Kenneth
K
Iacono
Aldo
A
Murray
John J
JJ
Crowe
Deborah
D
Johnson
Joyce E
JE
Ninan
Mathew
M
Milstone
Aaron P
AP
D000906:Antibodies; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D003167:Complement Activation; D015935:Complement C4b / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006084:Graft Rejection; D006085:Graft Survival; D006680:HLA Antigens / Q000737:chemistry; D006801:Humans; D000860:Hypoxia; D016756:Immunoglobulins, Intravenous / Q000737:chemistry; D007518:Isoantibodies; D008168:Lung / Q000473:pathology; D016040:Lung Transplantation / Q000276:immunology / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000096:biosynthesis*; D010949:Plasma / Q000378:metabolism; D013909:Thorax / Q000473:pathology; D013997:Time Factors; D014019:Tissue Donors; D014057:Tomography, X-Ray Computed; D014184:Transplantation, Homologous
D000906:Antibodies; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d