Proteasome inhibitor-based therapy for antibody-mediated rejection

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Presentation transcript:

Proteasome inhibitor-based therapy for antibody-mediated rejection R. Carlin Walsh, Rita R. Alloway, Alin L. Girnita, E. Steve Woodle Kidney International Volume 81, Issue 11, Pages 1067-1074 (June 2012) DOI: 10.1038/ki.2011.502 Copyright © 2012 International Society of Nephrology Terms and Conditions

Figure 1 26S Proteasome structure. Kidney International 2012 81, 1067-1074DOI: (10.1038/ki.2011.502) Copyright © 2012 International Society of Nephrology Terms and Conditions

Figure 2 Primary mechanisms of proteasome inhibitor-mediated immunomodulation. ER, endoplasmic reticulum; MHC, major histocompatibility complex; NF-κB, nuclear factor-kappa B; UPR, unfolded protein response. Kidney International 2012 81, 1067-1074DOI: (10.1038/ki.2011.502) Copyright © 2012 International Society of Nephrology Terms and Conditions

Figure 3 Response of donor-specific anti-human leukocyte antigen (HLA) antibody (DSA) levels to treatment with bortezomib (expressed as molecules of equivalent soluble fluorescence (MESF)). The blue line represents immunodominant DSA (HLA DR14) and other colored lines represent non-immunodominant DSA. Renal allograft biopsy pre-treatment (PTD 13) demonstrates (a) mild acute tubular injury, mild glomerulitis, and mild inflammation of peritubular capillaries with no evidence of acute cellular rejection (ACR), and (b) immunostain for C4d shows strong diffuse peritubular and glomerular capillary deposition. Post-treatment (PTD 28) renal allograft biopsy in patient 1 demonstrates (c) no evidence of ACR, and (d) immunostain for C4d shows rare, faint peritubular capillary labeling and strong glomerular capillary deposition. Original magnification: (a, c) × 200; (b, d) × 400. PTD, post transplant day. Kidney International 2012 81, 1067-1074DOI: (10.1038/ki.2011.502) Copyright © 2012 International Society of Nephrology Terms and Conditions