title: HLA-specific antibodies are risk factors for lymphocytic bronchiolitis and chronic lung allograft dysfunction.
abstract: Bronchiolitis obliterans syndrome (BOS) represents a major limitation in lung transplantation. While acute rejection is widely considered the most important risk factor for BOS, the impact of HLA-specific antibodies is less understood. Of 51 lung recipients who were prospectively tested during a 4.2 +/- 1.6-year period, 14 patients developed HLA-specific antibodies. A multi-factorial analysis was performed to correlate the prevalence of BOS with HLA antibodies, persistent-recurrent acute rejection (ACR-PR), lymphocytic bronchiolitis, and HLA-A, -B, and -DR mismatches. HLA-specific antibodies were associated with ACR-PR (10/14 vs. 11/37 with no antibodies, p < 0.05), lymphocytic bronchiolitis (8/14 vs. 10/37, p < 0.05), and BOS (10/14, vs. 9/37, p < 0.005). Other risk factors for BOS were: lymphocytic bronchiolitis (13/18 vs. 6/33 with no lymphocytic bronchiolitis, p < 0.0001), ACR-PR (12/21 vs. 7/30 with no ACR-PR, p < 0.05), and the number of HLA-DR mismatches (1.7 +/- 0.48 in BOS vs. 1.2 +/- 0.63 without BOS, p < 0.05). The presence of antibodies exhibited a cumulative effect on BOS when it was associated with either lymphocytic bronchiolitis or ACR-PR. The complex relationship between the development of HLA antibodies and acute and chronic lung allograft rejection determines the importance of post-transplant screening for HLA-specific antibodies as a prognostic element for lung allograft outcome.
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Alin L
authors.initials: AL
authors.lastname: Girnita
authors.forename: Rene
authors.initials: R
authors.lastname: Duquesnoy
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Yousem
authors.forename: Aldo T
authors.initials: AT
authors.lastname: Iacono
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Corcoran
authors.forename: Manuela
authors.initials: M
authors.lastname: Buzoianu
authors.forename: Bruce
authors.initials: B
authors.lastname: Johnson
authors.forename: Kathy J
authors.initials: KJ
authors.lastname: Spichty
authors.forename: James H
authors.initials: JH
authors.lastname: Dauber
authors.forename: Gilbert
authors.initials: G
authors.lastname: Burckart
authors.forename: Bartley P
authors.initials: BP
authors.lastname: Griffith
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: McCurry
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
mesh_terms: D001706:Biopsy; D001988:Bronchiolitis / Q000276:immunology*; D001989:Bronchiolitis Obliterans / Q000209:etiology*; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D006084:Graft Rejection; D006680:HLA Antigens / Q000737:chemistry* / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016040:Lung Transplantation / Q000379:methods*; D008214:Lymphocytes / Q000276:immunology; D008954:Models, Biological; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors; D013997:Time Factors; D014181:Transplantation Immunology
chemical_list: D006680:HLA Antigens; D006684:HLA-DR Antigens