Supplementary Appendix

Transcription

1 Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Jordan SC, Lorant T, Choi J, et al. IgG endopeptidase in highly sensitized patients undergoing transplantation. N Engl J Med 2017;377: DOI: /NEJMoa

2 Supplementary Materials Table of Contents Pg 1: Table of Contents & List of Investigators Pg 2: Figure S1 Summary of Banff 2013 Criteria For Diagnosing Antibody Mediated Rejection in Kidney Allografts Pg 3: Figure S2 Dynamics of Total IgG, Fc and F(ab )2 fragments in The Sera of IdeS treated Patients. Pg 4: Figure S3 - SDC Lymphocyte Population Post Ides for Sweden Pg 5: Figure S4A Human Leukocyte Antigen Antibodies and Non-donor specific antibodies dynamics after Ides treatment and transplantation in Swedish Patients Pg 6: Figure S4B Human Leukocyte Antigen Antibodies and Non-donor specific antibodies dynamics after Ides treatment and transplantation in US Patients Investigators of This Manuscript and Supplementary Appendix: Stanley C. Jordan, MD 1,2,5, Tomas Lorant, MD 6, Jua Choi, Pharm.D. 1,2 Christian Kjellman, PhD 12, Lena Winstedt, PhD 12, Mats Bengtsson, MD 9, Xiaohai Zhang, PhD 3, Torsten Eich MD 7, Mieko Toyoda, PhD 1,5, Britt-Marie Eriksson, MD 8, Shili Ge, PhD 1,5, Alice Peng, MD 1,2, Sofia Järnum PhD 12, Kathryn J Wood, DPhil 10, Torbjorn Lundgren, MD 11, Lars Wennberg, MD 11, Lars Bäckman, MD 6, Erik Larsson, MD 9, Rafael Villicana, MD 1,2, Joe Kahwaji, MD 1,2, Sabrina Louie, MPH 1,2, Alexis Kang, BS 1,2, Mark Haas, MD 4, PhD, Cynthia Nast, MD 4, Ashley Vo, Pharm.D 1,2 and Gunnar Tufveson, MD 6. Comprehensive Transplant Center 1, Transplant Immunotherapy Program 2, HLA Laboratory 3, Department of Pathology 4 and Transplant Immunology Laboratory 5 Cedars-Sinai Medical Center, Los Angeles, CA , Department of Surgical Sciences, Section of Transplantation Surgery 6, Department of Immunology, Genetics and Pathology, Section of Clinical Immunology 7, Department of Medical Sciences, Section of Infectious Diseases 8, Department of Immunology, Genetics and Pathology, Section of Molecular and Morphological Pathology 9, Uppsala University, Uppsala, Sweden, Nuffield Department of Surgical Sciences, Oxford University, Oxford UK 10, Division of Transplantation Surgery, CLINTEC, Karolinska Institutet, and Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden 11, and Hansa Medical AB 12, Lund, Sweden. Both investigators share first authorship. Both investigators share senior authorship. 1

3 Figure S1 Summary of Banff 2013 Criteria for Diagnosing Antibody Mediated Rejection in Kidney Allografts 2

4 Figure S2 Mean Total IgG, F(ab )2 and Fc Fragments Pre- and Post- IdeS Measured with ELISA This figure shows the mean total IgG, F(ab )2 and Fc fragment measured with ELISA (n=10 patients) pre- and post-ides treatment. 3

5 Figure S3 Box Plot of Total Lymphocyte Count in Blood Samples Before and After Transplant In the Swedish study the total lymphocyte count was reduced in all patients treated with eatg demonstrating that the induction therapy worked as expected. Although not shown lymphocyte depletion with alemtuzumab in US IdeS treated patients were similar to that reported below. Box plot of total lymphocyte count in blood samples collected before and at consecutive time-points following IdeS treatment from patients treated with eatg for induction (n=8). 4

6 Figure S4A Human Leukocyte Antigen Antibodies and Non-Donor-Specific Antibodies Dynamics after IdeS Treatment and Transplantation in Swedish Patients Three representative patients from the Swedish study. Patient #1 was dosed with 0.25 mg/kg IdeS and patients #2 and #3 with 0.50 mg/kg IdeS. Top: Box plots of non-dsa HLA antibodies [LABScreen Mean Flourescent Intensity (MFI) data] having a pre-dose MFI >1100 (cut-off in study). Below: MFI of individual DSAs from corresponding patients. 5

7 Figure S4B Human Leukocyte Antigen Antibodies and Non-Donor-Specific Antibodies Dynamics after IdeS Treatment and Transplantation in US Patients Three representative patients from the US study are shown. All patients received 0.24 mg/kg IdeS. Top: Box plots of non-dsa HLA antibodies having a pre-dose MFI >2500 (cut-off in study). Below: MFI of individual DSAs from corresponding patients. After IdeStreatment the MFI is reported as 0 if below 2500 MFI study specific cut-offs. Horizontal lines represent median MFI, boxes represent 25th and 75th percentile and vertical lines represent 10th and 90th percentile MFI. Dots are MFI of individual HLAs above or below the percentiles. The P-values at first significant difference between pre and post dose are given. NS is the time-point when there is no longer significance between pre and 6

8 post dose. Statistics: Friedman test with Dunn's multiple comparison test. The number (N) of HLAs having an MFI above the cut-off at 1100 is given in graph. 7