title: Immunologic monitoring in lung allograft recipients.
abstract: To identify patients with increased risk of chronic lung allograft rejection, we assessed the utility of an in vitro biopsy-derived lymphocyte growth assay and serum anti-HLA antibody screening as a complement to currently available methods of monitoring lung allograft recipients. Lymphocyte growth assay was performed on bronchoscopic fragments of tissue cultured in medium with rIL-2. Seventy-nine biopsies from 31 lung transplant recipients were tested by lymphocyte growth assay, and results were correlated with histopathology findings. Positive lymphocyte growth was found in 12/26 (46%) episodes of acute rejection, 5/44 biopsies without rejection (11%), and 0/9 episodes of bronchitis. Positive lymphocyte growth was seen in 7/16 (44%) grade A1 rejections and in 5/10 (50%) grade A2 rejections, as opposed to only 5/44 (11%) grade A0 (no rejection) biopsies (P < 0.01 for both A1 and A2 with respect to A0). Actuarial probability of remaining free from obliterative bronchiolitis (OB)* tended to be higher in patients who did not exhibit lymphocyte growth in biopsies. Sequential samples of sera obtained at the time of the biopsy were screened for lymphocytotoxic anti-HLA antibodies. Twenty-two of 44 recipients (50%) developed anti-HLA antibodies during the first postoperative year, exhibiting greater than 10% reactivity to an HLA reference panel of lymphocytes in four or more consecutive serum samples. Actuarial survival of lung allograft recipients with anti-HLA antibodies (n = 22) was lower than in those without anti-HLA antibodies (n = 22; P = 0.03). Of the 22 antibody producers, 7/12 died as a consequence of OB. Of the 22 non-antibody-producers, 1/2 deaths occurred as a consequence of OB. Anti-HLA antibodies were present in 9/11 instances of OB (82% sensitivity) and in 13/33 patients without OB (61% specificity; P = 0.03). These data indicate that lung transplant recipients with positive lymphocyte growth and anti-HLA antibodies are at an increased risk of chronic allograft rejection.
authors.affiliation: Department of Medicine, College of Physicians & Surgeons of Columbia University, New York, New York 10032, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Schulman
authors.forename: E K
authors.initials: EK
authors.lastname: Ho
authors.forename: E F
authors.initials: EF
authors.lastname: Reed
authors.forename: C
authors.initials: C
authors.lastname: McGregor
authors.forename: C R
authors.initials: CR
authors.lastname: Smith
authors.forename: E A
authors.initials: EA
authors.lastname: Rose
authors.forename: N M
authors.initials: NM
authors.lastname: Suciu-Foca
mesh_terms: D000906:Antibodies / Q000097:blood; D002455:Cell Division; D002478:Cells, Cultured; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies; D006680:HLA Antigens