PMID- 15268735 OWN - NLM STAT- MEDLINE DCOM- 20050214 LR - 20230124 IS - 1600-6135 (Print) IS - 1600-6135 (Linking) VI - 4 IP - 8 DP - 2004 Aug TI - Acute humoral rejection of human lung allografts and elevation of C4d in bronchoalveolar lavage fluid. PG - 1323-30 AB - 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. FAU - Miller, Geraldine G AU - Miller GG AD - Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. geraldine.miller@vanderbilt.edu FAU - Destarac, Luis AU - Destarac L FAU - Zeevi, Adriana AU - Zeevi A FAU - Girnita, Alin AU - Girnita A FAU - McCurry, Kenneth AU - McCurry K FAU - Iacono, Aldo AU - Iacono A FAU - Murray, John J AU - Murray JJ FAU - Crowe, Deborah AU - Crowe D FAU - Johnson, Joyce E AU - Johnson JE FAU - Ninan, Mathew AU - Ninan M FAU - Milstone, Aaron P AU - Milstone AP LA - eng GR - GM15431/GM/NIGMS NIH HHS/United States GR - HL53771/HL/NHLBI NIH HHS/United States GR - HL65189/HL/NHLBI NIH HHS/United States GR - M01 RR00095/RR/NCRR NIH HHS/United States PT - Case Reports PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Transplant JT - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JID - 100968638 RN - 0 (Antibodies) RN - 0 (HLA Antigens) RN - 0 (Immunoglobulins, Intravenous) RN - 0 (Isoantibodies) RN - 0 (Peptide Fragments) RN - 80295-50-7 (Complement C4b) RN - 80295-52-9 (complement C4d) SB - IM MH - Antibodies MH - Asthma/*metabolism/pathology MH - Biopsy MH - Bronchoalveolar Lavage Fluid/*immunology MH - Complement Activation MH - Complement C4b/*biosynthesis MH - Enzyme-Linked Immunosorbent Assay MH - Flow Cytometry MH - Graft Rejection MH - Graft Survival MH - HLA Antigens/chemistry MH - Humans MH - Hypoxia MH - Immunoglobulins, Intravenous/chemistry MH - Isoantibodies MH - Lung/pathology MH - Lung Transplantation/immunology/*methods MH - Male MH - Middle Aged MH - Peptide Fragments/*biosynthesis MH - Plasma/metabolism MH - Thorax/pathology MH - Time Factors MH - Tissue Donors MH - Tomography, X-Ray Computed MH - Transplantation, Homologous EDAT- 2004/07/23 05:00 MHDA- 2005/02/16 09:00 CRDT- 2004/07/23 05:00 PHST- 2004/07/23 05:00 [pubmed] PHST- 2005/02/16 09:00 [medline] PHST- 2004/07/23 05:00 [entrez] AID - S1600-6135(22)07914-X [pii] AID - 10.1111/j.1600-6143.2004.00508.x [doi] PST - ppublish SO - Am J Transplant. 2004 Aug;4(8):1323-30. doi: 10.1111/j.1600-6143.2004.00508.x.