The development of donor specific antibodies (DSA) reacting to mismatched donor class I and class II HLA is a prominent risk factor for kidney graft loss. Over the past few years our lab investigated the implications of a different type of antibodies referred to as natural antibodies (Nabs) in the outcome of kidney transplant alongside DSA. These antibodies are polyreactive IgG binding to multiple immunogenic determinants, including oxidized epitopes. Here, we assessed Nabs in 1462 serum specimens collected from 635 patients immediately pre-transplant and either at time of biopsy proven rejection within the first year post-transplant or at one year post-transplant in patients without immunological event. This large prospective observational cohort from Necker Hospital in Paris, France, includes patients transplanted between 2005 and 2010. All specimens were tested blindly from the patient clinical information. Nabs were assessed by ELISA through their reactivity to malondialdehyde (MDA). A univariate Cox regression model identified the development of Nabs post-transplant (>50% increase in reactivity to MDA) as a significant risk factor for graft loss (p=0.0078; HR=2.372). A multivariate Cox confirmed the development of Nabs as a risk factor independent from DSA. Furthermore, the development of Nabs synergized with DSA (p=0.0008, Figure 1) resulting in increased risk of kidney graft loss. These findings support an association of Nabs with kidney transplant survival and suggest their potential implication in immune mechanisms of rejection.

CITATION INFORMATION: See S, Loupy A, Aubert O, Veras Y, Lebreton X, Gao B, Legendre C, Anglicheau D, Zorn E. Generation of Natural Antibodies Post Transplant and Association with Kidney Allograft Loss. Am J Transplant. 2017;17 (suppl 3).

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