Epithelial cell polarity and improved early outcomes in delayed graft function: a pilot study of polyclonal vs monoclonal antibodies.
BACKGROUND
Polyclonal antibody preparations contain antibodies that bind not only to molecules on circulating lymphocytes but also to other sites that bear similar antigens. We hypothesized that this extra-antibody effect would increase the number of intact tubular epithelial cells in organs at high risk for delayed graft function (DGF).


METHODS
We used immunohistochemistry to examine serial biopsy samples (time 0 and 7-10 days after transplantation) in 18 kidney transplant recipients with DGF. These individuals received either polyclonal rabbit antithymocyte sera or a monoclonal humanized anti-CD25 antibody as induction immunosuppression. We also examined their early clinical course over 6 months.


RESULTS
Individuals treated with the polyclonal preparation demonstrated greater preservation of kidney epithelial cell polarity manifested by more intense and more localized basolateral distribution of E-cadherin (P = 0.016), beta-catenin (P = 0.008) and Na-K ATPase (P = 0.02). These individuals were also more likely to maintain greater estimated glomerular filtration rates (eGFRs) at follow-up than patients treated with an anti-CD25 monoclonal antibody (6 month eGFR polyclonal: 55.5+/-7.12 ml/min vs monoclonal: 43.33+/-6.48 ml/min; P = 0.002).


CONCLUSIONS
Though a pilot study, these data suggest that a purified polyclonal antibody preparation may help conserve functional kidney mass during DGF with potential benefits on transplant function overall.
Becker
Yolanda T
YT
Department of Surgery, University of Wisconsin-Madison, Madison, WI 53792, USA.
Hofmann
R Michael
RM
Yracheta
Joseph
J
Friedl
Andreas
A
Becker
Bryan N
BN
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D000077552:Basiliximab; D015820:Cadherins / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects*; D004847:Epithelial Cells; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D015820:Cadherins; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab