title: Pregnancy-induced HLA antibodies respond more vigorously after renal transplantation than antibodies induced by prior transplantation.
abstract: Acute antibody mediated rejection after HLA-specific antibody incompatible renal transplantation is related to donor specific HLA antibody (DSA) levels. DSA levels may rise sharply after transplant, and aim of this study was to examine changes in DSA levels, particularly according to the primary sensitising event. Changes in 220 HLA specificities in 64 patients over the first 30days after transplantation were evaluated using microbead assays. The greatest increase from pre-treatment to peak DSA levels was seen in pregnancy-stimulated specificities, median (IQR) increase in MFI of 1981 (94-5870). The next highest increase was for those sensitised by transplant with repeat HLA epitope mismatch, at 546 (-308-2698) (p<0.01). The difference was especially marked when the pre-treatment antibody level was low; with pre-treatment MFI <1000, peak level was >1000 in 19/26 (73%) of pregnancy stimulated specificities, compared with 9/29 (31%) for all others (p<0.001). DSA production to specificities stimulated by previous pregnancy was marked, even from very low pre-transplant levels. By contrast, there was a lower rate of antibody resynthesis to specificities repeated from previous transplants, both at antigen and epitope levels.
authors.affiliation: Transplant Unit, University Hospitals Coventry and Warwickshire, Coventry, West Midlands, United Kingdom. Electronic address: Robert.Higgins@uhcw.nhs.uk.
authors.forename: Rob
authors.initials: R
authors.lastname: Higgins
authors.affiliation: Histocompatibility Laboratory, National Blood and Transplant, Birmingham, West Midlands, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Lowe
authors.affiliation: Transplant Unit, University Hospitals Coventry and Warwickshire, Coventry, West Midlands, United Kingdom; Clinical Sciences Research Laboratory, Warwick Medical School, University of Warwick, Coventry, West Midlands, UK.
authors.forename: Sunil
authors.initials: S
authors.lastname: Daga
authors.affiliation: Histocompatibility Laboratory, National Blood and Transplant, Birmingham, West Midlands, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Hathaway
authors.affiliation: Histocompatibility Laboratory, National Blood and Transplant, Birmingham, West Midlands, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Williams
authors.affiliation: Transplant Unit, University Hospitals Coventry and Warwickshire, Coventry, West Midlands, United Kingdom.
authors.forename: F T
authors.initials: FT
authors.lastname: Lam
authors.affiliation: Transplant Unit, University Hospitals Coventry and Warwickshire, Coventry, West Midlands, United Kingdom.
authors.forename: Habib
authors.initials: H
authors.lastname: Kashi
authors.affiliation: Transplant Unit, University Hospitals Coventry and Warwickshire, Coventry, West Midlands, United Kingdom.
authors.forename: Lam Chin
authors.initials: LC
authors.lastname: Tan
authors.affiliation: Transplant Unit, University Hospitals Coventry and Warwickshire, Coventry, West Midlands, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Imray
authors.affiliation: Transplant Unit, University Hospitals Coventry and Warwickshire, Coventry, West Midlands, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Fletcher
authors.affiliation: Transplant Unit, University Hospitals Coventry and Warwickshire, Coventry, West Midlands, United Kingdom.
authors.forename: Nithya
authors.initials: N
authors.lastname: Krishnan
authors.affiliation: Transplant Unit, University Hospitals Coventry and Warwickshire, Coventry, West Midlands, United Kingdom.
authors.forename: Pat
authors.initials: P
authors.lastname: Hart
authors.affiliation: Transplant Unit, University Hospitals Coventry and Warwickshire, Coventry, West Midlands, United Kingdom; Clinical Sciences Research Laboratory, Warwick Medical School, University of Warwick, Coventry, West Midlands, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zehnder
authors.affiliation: Histocompatibility Laboratory, National Blood and Transplant, Birmingham, West Midlands, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Briggs
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000628:therapy; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D010956:Plasmapheresis / Q000379:methods; D011247:Pregnancy; D013997:Time Factors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies
keywords: Antibody incompatible kidney transplantation; Antibody mediated rejection; HLA Class 1; HLA Class 2; HLA antibodies; Pregnancy; Transfusion