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U N I V E R S I T Ä T S M E D I Z I N B E R L I N

U N I V E R S I T Ä T S M E D I Z I N B E R L I N. Antibody Effector Functions and Their Clinical Relevance. Nils Lachmann. Terasaki Festschrift 2014. Introduction. Transplantation HLA mismatches. HLA antibodies. HLA Antibodies and TX Outcome. Objectives. donor specificity.

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U N I V E R S I T Ä T S M E D I Z I N B E R L I N

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  1. U N I V E R S I T Ä T S M E D I Z I N B E R L I N Antibody Effector Functions and Their Clinical Relevance Nils Lachmann Terasaki Festschrift 2014

  2. Introduction Transplantation HLA mismatches HLA antibodies

  3. HLA Antibodiesand TX Outcome

  4. Objectives donorspecificity Determinantsof relative pathogenicityof posttransplant HLA antibodies? antibodylevel CDC ADCC Phagocytosis complementbinding MFI IgGsubclass celldeath rejection

  5. Patient Population Consecutive kidney transplant recipients from out-patient clinic n = 1179 n = 57 POD < 90th day n = 26 impaired graft function (SCr > 3 mg/dl) n = 17 TX < 1980 n = 4 follow-up < 100 days Cross-sectional HLAab testing n = 1075 Insufficient TX data n = 287 insufficientamountofstoredserum DSA / MFI n = 788 IgG subclass, C1q IgGSubclass / C1q

  6. Methods DSA / MFI C1q • LABScreen Single Antigen I/II • HLA-A/B/C/DR/DQ • untreatedserum, MFI cutoff = 1,000 • Endpoints: eGFR<30, AMR, graft loss IgGSubclasses

  7. Methods α2 peptide human mAb (SN230G6) from A. Mulder (Leiden) IgG1, κ anti-HLA-A2/B57/B58 α1 62G β2m

  8. 1: DonorSpecificity DSA I II NDSA I+II

  9. 2: Quantificationby MFI

  10. 3: IgGSubclasses IgG1/2/3/4 46% IgG1/3 49% HLA cl. II IgG2/4 5% HLA cl. I

  11. 4: C1q-DSA

  12. Conclusions: Relative Pathogenicity 1° Donorspecificity 3° MFI 2° C1q 3° IgGsubclasses • Posttransplant RiskStrata: • DSA+/C1q+> DSA+/C1q- > NDSA+ >> HLAab- • (irresp. IgG1-4& MFI) Thankyou

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