FLOW CYTOMETRY-DETECTED IgG IS NOT A CONTRAINDICATION TO RENAL TRANSPLANTATION

Abstract

These data suggest that, after a negative donor-specific IgG-AHG XM, an IgG-positive FCXM is not a contraindication to transplantation. The presence of IgM may be beneficial in reducing the occurrence of rejection episodes and improving graft survivals.

Naturally Occurring IgM Anti-Leukocyte Autoantibodies (IgM-ALA) Inhibit T Cell Activation and Chemotaxis

“…These data, together with previously published data, would indicate that IgM-ALA may have a role in inhibiting or attenuating the inflammatory response mediated by acute rejections (27)(28)(29)(30)(31). Presence of high IgM-ALA did not corelate with age, sex, race, renal disease causing ESRD or pretransplant exposure to CMV and EBV viruses.…”

“…However clues on the potential identity of some of these receptors became apparent when we attempted to explain certain clinical observations in human kidney and heart transplants. Allograft recipients with high levels of IgM-ALA were found to have significantly better allograft survival and fewer rejections even during the precyclosporin era (27)(28)(29)(30)(31). Recognizing that rejection in an allograft is a T cell mediated inflammatory process, we hypothesized that IgM-ALA mediated these inhibitory effects by binding to leukocyte receptors involved in T cell activation and leukocyte chemotaxis.…”

“…Human kidney and heart transplants performed in the subset (approx. 30%) of patients having high levels of IgM-ALA have a lower incidence of acute rejections and of less severity, thus permitting better graft survival (27)(28)(29)(30)(31). The protective effect of IgM-ALA in allograft transplantation together with the observation that IgM-ALA nonspecifically increase in various inflammatory and infective states led us to hypothesize whether the increased production of IgM-ALA has a role in inhibiting T cell activation and attenuating the inflammatory response by binding to certain cell membrane receptors important in the inflammatory process i.e., receptors that activate T lymphocytes and receptors that are important for chemotaxis.…”

High negative predictive value of an amplified flow cytometry crossmatch before living donor kidney transplantation

“…Previous studies yielded contrasting results, describing an association of a positive FCXM result with (antibody-mediated) allograft rejection [3,4,11,13] or allograft loss [3,5,11,12], or, by contrast no association with allograft rejection [6 -10] or allograft loss [7,8]. These discrepancies possibly result from differences in the FCXM procedure or analysis or from differences in patient care.…”

Back to the future: application of contemporary technology to long-standing questions about the clinical relevance of human leukocyte antigen-specific alloantibodies in renal transplantation

“…By restricting FCXM to sensitized recipients, the sensitivity of cross-matching is improved and a positive result is more likely to be the result of clinically relevant antibodies. However, it should be pointed out that not all transplant clinicians regard a CDC-negative, FCXMpositive result as a contraindication to renal transplantation and argue that any additional immunological risk can be overcome by modern immunosuppressive therapy [17].…”