title: The big picture: A case report of antibody mediated rejection and treatment after lung transplantation illustrating the need to correlate laboratory findings with clinical status.
abstract: We report the case of a patient who developed respiratory failure in the presence of de novo donor-specific antibody (DSA) two years after lung transplantation, following recurrent acute cellular rejection. The patient underwent salvage therapy with plasma exchange, intravenous immunoglobulins, and proteasome inhibitor carfilzomib (CFZ). DSA was detected prior to admission for antibody-mediated rejection by single antigen bead Luminex (SAB) testing and indicated the presence of a DQ3 pattern (DQ7, DQ8, and DQ9). The patient initially responded to CFZ-based treatment with a decline in DQ3-DSA strengths, but DQ7-DSA persisted at low-levels. However, the DQ7-C1q reactivity that was absent after therapy recovered, indicating a potential "prozone" effect on SAB testing. Treating sera with dithiothreitol/ heat and ethylenediaminetetraacetic acid was able to relieve the "prozone" effect, resulting in an increased DQ7 immunoglobulin G (IgG) mean fluorescence intensity. HLAMatchmaker eplet analysis suggested reactivity towards the DQB1* eplet 55PPP expressed on all DQ3 antigens and DQB1* eplet 45EV(DQ7). In this case, we illustrate the functional diversity of DQ3/DQ7-specific DSA reactivity patterns obtained by IgG-SAB and C1q-SAB assays and determined the eplet repertoire using HLAMatchmaker. DSA analysis should include tests to evaluate DSA strength, titer, and function, along with communications with clinical colleagues to correlate laboratory findings with clinical parameters.
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
authors.forename: Marilyn
authors.initials: M
authors.lastname: Marrari
authors.forename: John
authors.initials: J
authors.lastname: Lunz
authors.forename: Jon
authors.initials: J
authors.lastname: Lomago
authors.forename: Kurt
authors.initials: K
authors.lastname: Johnson
authors.forename: Lawrence
authors.initials: L
authors.lastname: Jelinek
authors.forename: Donald
authors.initials: D
authors.lastname: Foster
authors.forename: Christian
authors.initials: C
authors.lastname: Bermudez
authors.forename: John
authors.initials: J
authors.lastname: McDyer
authors.forename: Joseph
authors.initials: J
authors.lastname: Pilewski
authors.forename: Christopher
authors.initials: C
authors.lastname: Ensor
mesh_terms: D000328:Adult; D000939:Epitopes / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D006680:HLA Antigens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D010951:Plasma Exchange; D061988:Proteasome Inhibitors / Q000627:therapeutic use; D017434:Protein Structure, Tertiary; D012131:Respiratory Insufficiency / Q000209:etiology / Q000276:immunology* / Q000473:pathology
chemical_list: D000939:Epitopes; D006680:HLA Antigens; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D061988:Proteasome Inhibitors