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2016 ; 196
(10
): 4075-81
Nephropedia Template TP
gab.com Text
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Generation of Catalytic Antibodies Is an Intrinsic Property of an Individual s
Immune System: A Study on a Large Cohort of Renal Transplant Patients
#MMPMID27067006
Mahendra A
; Peyron I
; Thaunat O
; Dollinger C
; Gilardin L
; Sharma M
; Wootla B
; Rao DN
; Padiolleau-Lefevre S
; Boquet D
; More A
; Varadarajan N
; Kaveri SV
; Legendre C
; Lacroix-Desmazes S
J Immunol
2016[May]; 196
(10
): 4075-81
PMID27067006
show ga
Renal transplant is the treatment of choice for patients with terminal end-stage
renal disease. We have previously identified low levels of catalytic IgG as a
potential prognosis marker for chronic allograft rejection. The origin and
physiopathological relevance of catalytic Abs is not well understood, owing to
the fact that catalytic Abs have been studied in relatively small cohorts of
patients with rare diseases and/or without systematic follow-up. In the current
study, we have followed the evolution of the levels of catalytic IgG in a large
cohort of renal transplant patients over a 2-y period. Our results demonstrate
that, prior to transplant, patients with renal failure present with heterogeneous
levels of IgG hydrolyzing the generic
proline-phenylalanine-arginine-methylcoumarinamide (PFR-MCA) substrate. PFR-MCA
hydrolysis was greater for patients' IgG than for a therapeutic preparation of
pooled IgG from healthy donors. Renal transplant was marked by a drastic decrease
in levels of catalytic IgG over 3 mo followed by a steady increase during the
next 21 mo. Patients who displayed high levels of catalytic IgG pretransplant
recovered high levels of catalytic Abs 2 y posttransplant. Interestingly,
IgG-mediated hydrolysis of a model protein substrate, procoagulant factor VIII,
did not correlate with that of PFR-MCA prior transplantation, whereas it did 12
mo posttransplant. Taken together, our results suggest that the level of
circulating catalytic IgG under pathological conditions is an intrinsic property
of each individual's immune system and that recovery of pretransplant levels of
catalytic IgG is accompanied by changes in the repertoire of target Ags.