title: Complement-Binding Donor-Specific Anti-HLA Antibodies and Risk of Primary Graft Failure in Hematopoietic Stem Cell Transplantation.
abstract: Detection of donor-specific anti-HLA antibodies (DSA) has been associated with graft rejection in all forms of transplantation. The mechanism by which DSA increase the risk of graft failure remains unclear. We hypothesized that complement-binding DSA are associated with engraftment failure in hematopoietic stem cell transplantation (HSCT) and analyzed 122 haploidentical transplant recipients tested prospectively for DSA. Retrospective analysis to detect C1q binding DSA (C1q+DSA) was performed on 22 allosensitized recipients. Twenty-two of 122 patients (18%) had DSA, 19 of which were women (86%). Seven patients with DSA (32%) rejected the graft. Median DSA level at transplant for patients who failed to engraft was 10,055 mean fluorescence intensity (MFI) versus 2065 MFI for those who engrafted (P = .007). Nine patients with DSA were C1q positive in the initial samples with median DSA levels of 15,279 MFI (range, 1554 to 28,615), compared with 7 C1q-negative patients with median DSA levels of 2471 MFI (range, 665 to 12,254) (P = .016). Of 9 patients who were C1q positive in the initial samples, 5 patients remained C1q positive at time of transplant (all with high DSA levels [median, 15,279; range, 6487 to 22,944]) and experienced engraftment failure, whereas 4 patients became C1q negative pretransplant and all engrafted the donor cells (P = .008). In conclusion, patients with high DSA levels (>5000 MFI) and complement-binding DSA antibodies (C1q positive) appear to be at much higher risk of primary graft failure. The presence of C1q+DSA should be assessed in allosensitized patients before HSCT. Reduction of C1q+DSA levels might prevent engraftment failure in HSCT.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: sciurea@mdanderson.org.
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Ciurea
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Thall
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Denái R
authors.initials: DR
authors.lastname: Milton
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Titus H
authors.initials: TH
authors.lastname: Barnes
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Piyanuch
authors.initials: P
authors.lastname: Kongtim
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yudith
authors.initials: Y
authors.lastname: Carmazzi
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Asdrúbal A
authors.initials: AA
authors.lastname: López
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Dianne Y
authors.initials: DY
authors.lastname: Yap
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Uday
authors.initials: U
authors.lastname: Popat
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondon
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lichtiger
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Fleur
authors.initials: F
authors.lastname: Aung
authors.affiliation: Department of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Vahid
authors.initials: V
authors.lastname: Afshar-Kharghan
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Pathology, Stanford University, Palo Alto, California.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernández-Viña
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Kai
authors.initials: K
authors.lastname: Cao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods*; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: Buffy coat; C1q; Complement-binding DSA; Desensitization; Donor-specific anti-HLA antibodies; Graft rejection; Hematopoietic stem cell transplantation