Abstract
Catalytic antibodies are immunoglobulins endowed with enzymatic activity. Catalytic IgG has been reported in several human autoimmune and inflammatory diseases. In particular, low levels of catalytic IgG have been proposed as a prognostic marker for chronic allograft rejection in patients undergoing kidney transplant. Kidney allograft is a treatment of choice for patients with end-stage renal failure. Intravenous immunoglobulins, a therapeutic pool of human IgG, is used in patients with donor-specific antibodies, alone or in conjunction with other immunosuppressive treatments, to desensitize the patients and prevent the development of acute graft rejection. Here, we followed for a period of 24 months the levels of catalytic IgG towards the synthetic peptide Pro-Phe-Arg-methylcoumarinimide in a large cohort of patients undergoing kidney transplantation. Twenty-four percent of the patients received IVIg at the time of transplantation. Our results demonstrate a marked reduction in levels of catalytic antibodies in all patients three months following kidney transplant. The decrease was significantly pronounced in patients receiving adjunct IVIg therapy. The results suggests that prevention of acute graft rejection using intravenous immunoglobulins induces a transient reduction in the levels of catalytic IgG, thus potentially jeopardizing the use of levels of catalytic antibodies as a prognosis marker for chronic allograft nephropathy.
Highlights
Catalytic antibodies are immunoglobulins that are endowed with enzymatic activity [1]
Low levels of catalytic IgG 3 months following transplantation were predictive of chronic allograft nephropathy (CAN), the main cause for late allograft failure, 2 years down the lane, suggesting that IgG-mediated PFR-MCA hydrolysis may be used as a prognosis marker for CAN in renal-transplanted patients [22]
We have recently shown that an intensive day 0 prophylactic immunosuppressive strategy combining intravenous immunoglobulin (IVIg), anti-CD20 and plasmapheresis in this high-risk population is associated with a significant improvement in the long-term function and chronic antibody-mediated rejection rate [28]
Summary
Catalytic antibodies are immunoglobulins that are endowed with enzymatic activity [1]. Because catalytic antibodies in the human had been reported under pathological conditions, it was long thought that they are endowed with a pathogenic role, or that, at least, they are a hallmark of immune dysregulation and uncontrolled inflammation [12]. The antigen/substrate specificity of catalytic antibodies is promiscuous [16] and the latter are generally probed using surrogate synthetic peptide substrates [17]. Increased levels of IgG capable of hydrolyzing the synthetic tri-peptide substrate for serine proteases - proline-phenylalanine-arginine-methyl-coumarinamide (PFR-MCA), were found at the time of diagnosis in patients who had survived septic shock three weeks later [21]. Low levels of catalytic IgG 3 months following transplantation were predictive of chronic allograft nephropathy (CAN), the main cause for late allograft failure, 2 years down the lane, suggesting that IgG-mediated PFR-MCA hydrolysis may be used as a prognosis marker for CAN in renal-transplanted patients [22]
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