IVIg Treatment Reduces Catalytic Antibody Titers of Renal Transplanted Patients

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.

Generation of Catalytic Antibodies Is an Intrinsic Property of an Individual’s Immune System: A Study on a Large Cohort of Renal Transplant Patients

“…A specific assessment of the effects of steroids on the levels of catalytic IgG was not possible, since all patients were administered with at least one form of steroid. Of note, in a previous analysis using the same patients cohort (16), we showed that the decrease in levels of catalytic IgG was greater in the case of patients who were treated with repeated doses of IVIg post-transplant. We had proposed that the further reduction of catalytic IgG in IVIg-treated patients could result either from a dilution of the patients’ IgG by the administered IVIg or from a direct immunomodulatory effect of IVIg on the patients’ immune system (16).…”

B Cells and Antibodies in Transplantation

“…This hypothesis is currently under evaluation in the prospective CATAPULT study. More recently, the same group showed that the levels of catalytic antibodies were heterogenous between renal transplanted patients (5). These levels drastically drop following transplantation and then slowly return to pre-transplant values, suggesting that this parameter is an intrinsic property of each individual's immune system (5).…”

Catalytic antibodies in patients with systemic lupus erythematosus

“…This was followed by immediate size-exclusion chromatography on a superose-12 column equilibrated with 50 mM Tris, 8 M urea, and 0.02 % NaN 3 (pH 7.7) to exclude potentially contaminating proteases, as detailed in our previous reports (6,10,28). IgG-containing fractions were then pooled and dialyzed against PBS-0.02% NaN 3 for 2 days with four changes of buffer at 4°C, followed by dialysis against catalytic buffer containing 5 mM CaCl 2 (pH 7.7) for 1 day with two buffer changes at 4°C, as previously described (32). The purity of IgG preparations was confirmed by SDS-PAGE and immunoblotting under non-reducing conditions.…”

“…The purity of IgG preparations was confirmed by SDS-PAGE and immunoblotting under non-reducing conditions. IgG was quantified by ultraviolet spectrophotometry (32).…”

“…IgG-mediated hydrolysis of PFR-MCA Purified IgG from 72 SLE patients and 45 healthy individuals was analyzed for the hydrolysis of PFR-MCA using a protocol established in the laboratory (32). In brief, IgG (66.67 nM) was mixed with 100 mM PFR-MCA (Peptide Institute, Inc.) in 40 µL of catalytic buffer containing 5 mM CaCl 2 (pH 7.7) in white 96-well U-bottom plates (Thermo Scientific) and incubated in the dark for 24 h at 37°C.…”