Humoral immunity to vimentin is associated with cardiac allograft injury in nonhuman primates.
Immunity to autologous protein has not previously been described following nonhuman primate cardiac transplant. Native hearts and cardiac allografts from cynomolgus monkeys were assessed by immunohistology for vimentin, a highly conserved intermediate filament protein. IgM and IgG to vimentin were measured in serial sera from untreated (n = 4) or cyclosporine (CsA)-treated (n = 8, 2 with ATG) cardiac allograft recipients, and in groups treated with anti-CD154 antibody with (n = 6) or without ATG (n = 28). IgM or IgG reactive with vimentin was elaborated within 30 days with unmodified acute rejection (3/4) or in CsA-treated animals (5/6). CD154 blockade did not prevent anti-vimentin IgM (14/28) but tended to delay the IgG response during therapy (anti-CD154: 8/28, p = 0.10 vs. CsA; anti-CD154+ATG: 2/6). CAV and alloantibody were seen in 25 of 26 animals with grafts surviving over 30 days, including seven animals without increasing anti-vimentin antibody. Anti-vimentin antibodies and vascular complement deposition were found in rejected hearts. Acute and chronic alloimmunity disrupt modulation of autoreactivity to vimentin through pathways, which are resistant to CsA, but may be partially regulated by CD154.
Azimzadeh
Agnes M
AM
Division of Cardiac Surgery, Department of Surgery, University of Maryland and Baltimore VAMC, Baltimore, MD 21201, USA. aazimzadeh@smail.umaryland.edu
Pfeiffer
Steffen
S
Wu
Guosheng S
GS
Schröder
Carsten
C
Zhou
Hui
H
Zorn
George L
GL
Kehry
Marilyn
M
Miller
Geraldine G
GG
Rose
Marlene L
ML
Pierson
Richard N
RN
D000818:Animals; D000917:Antibody Formation; D015153:Blotting, Western; D023201:CD40 Ligand / Q000096:biosynthesis; D002467:Cell Nucleus / Q000378:metabolism; D003167:Complement Activation; D015935:Complement C4b / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D006084:Graft Rejection; D006085:Graft Survival; D016027:Heart Transplantation / Q000379:methods*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007252:Influenza Vaccines / Q000494:pharmacology; D007518:Isoantibodies / Q000737:chemistry; D008252:Macaca fascicularis; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology; D011323:Primates; D013997:Time Factors; D014184:Transplantation, Homologous / Q000379:methods*; D014746:Vimentin / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D007252:Influenza Vaccines; D007518:Isoantibodies; D010446:Peptide Fragments; D014746:Vimentin; D023201:CD40 Ligand; D015935:Complement C4b; C032261:complement C4d; D016572:Cyclosporine