Can solid phase assays be better utilized to measure efficacy of antibody removal therapies?
Antibody removal therapies are used for patients with antibody-mediated-rejection or those requiring desensitization to become transplantable. Accurate measurement of antibody levels prior to, and during treatment, are required to choose the best therapeutic approach, and to provide measure of treatment efficacy. Currently, the FDA does not regard solid-phase assays for HLA-antibody identification as a reliable surrogate-marker for treatment efficacy. Serum samples from 40 patients (58 assays; >2200 positive data points) undergoing antibody-removal-therapies were tested as sample-pairs, pre- and post-treatment. MFI values of IgG and C1q single-antigen-bead assays were compared with antibody titer values (serial dilutions). Antibody reduction was tracked and the differences in pre-to-post-treatment values were calculated as delta-reduction of antibody levels. Dynamic patterns of titration studies reduced effects of serum-inherent inhibitory factors (prozone-like); eliminated over-saturation limitations, and provided better estimation of antibody-binding strength compared with the other methods. Moreover, delta-reduction of antibody values using titration studies was significantly more uniform compared with either IgG or C1q tests. Analyzing antibody results using only C1q positive or only higher MFI values did not change the overall magnitude of results. Overall, titration studies provided better estimate of responsiveness to treatment and thus can serve as companion to monitoring efficacy of antibody-removal therapies.
Transplant Immunology Laboratory, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Electronic address: a-tambur@northwestern.edu.
Anat R
AR
Tambur
Nephrology and Transplantation Service, Hôpital Saint-Louis, Paris, France.
Denis
D
Glotz
Transplant Immunology Laboratory, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Nancy D
ND
Herrera
Transplant Immunology Laboratory, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Erik N
EN
Chatroop
Transplant Immunology Laboratory, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Tal
T
Roitberg
Department of Medicine, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
John J
JJ
Friedewald
Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA, USA.
David
D
Gjertson
D000920:Antibody-Dependent Cell Cytotoxicity; D015922:Complement C1q / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007163:Immunosorbent Techniques; D007518:Isoantibodies / Q000378:metabolism*; D016030:Kidney Transplantation; D008991:Monitoring, Physiologic / Q000379:methods; D010956:Plasmapheresis
D006680:HLA Antigens; D007518:Isoantibodies; D015922:Complement C1q
AMR; Desensitization; HLA antibody; Luminex; MFI; SAB; Titer