Abstract
High dose intravenous immunoglobulin (IVIG) are widely used after kidney transplantation and its biological effect on T and B cell phenotype in the context of maintenance immunosuppression was not documented yet. We designed a monocentric prospective cohort study of kidney allograft recipients with anti-HLA donor specific antibodies (DSA) without acute rejection on screening biopsies treated with prophylactic high-dose IVIG (2 g/kg) monthly for 2 months. Any previous treatment with Rituximab was an exclusion criterion. We performed an extensive analysis of phenotypic and transcriptomic T and B lymphocytes changes and serum cytokines after treatment (day 60). Twelve kidney transplant recipients who completed at least two courses of high-dose IVIG (2 g/kg) were included in a median time of 45 (12–132) months after transplant. Anti-HLA DSA characteristics were similar before and after treatment. At D60, PBMC population distribution was similar to the day before the first infusion. CD8+ CD45RA+ T cells and naïve B-cells (Bm2+) decreased (P = 0.03 and P = 0.012, respectively) whereas Bm1 (mature B-cells) increased (P = 0.004). RORγt serum mRNA transcription factor and CD3 serum mRNA increased 60 days after IVIG (P = 0.02 for both). Among the 25 cytokines tested, only IL-18 serum concentration significantly decreased at D60 (P = 0.03). In conclusion, high dose IVIG induced limited B cell and T cell phenotype modifications that could lead to anti-HLA DSA decrease. However, no clinical effect has been isolated and the real benefit of prophylactic use of IVIG after kidney transplantation merits to be questioned.
Highlights
Intravenous immunoglobulin (IVIG) is the most highly used therapies for immunodeficiencies, autoimmune, and inflammatory diseases [1]
Protocol kidney allograft biopsies were performed in our center to follow kidney allograft recipients with donor specific antibodies (DSA) before transplantation and de novo anti-HLA DSA (dn DSA) as acute antibody mediated rejection (ABMR) is significantly higher in those patients [13, 14]
We provided here an extensive in vivo phenotypic and transcriptomic analysis in 12 patients treated with prophylactic high dose IVIG after kidney transplantation in patients with anti-HLA DSA without acute rejection and without any other treatment associated
Summary
Intravenous immunoglobulin (IVIG) is the most highly used therapies for immunodeficiencies, autoimmune, and inflammatory diseases [1]. Low-doses IVIG (0.3 g/kg) in common variable immunodeficiency induces. In the context of autoimmune and inflammatory diseases, dose of IVIG were elevated (2 g/kg) and their mechanisms of action were described to depend on Fc and/or F(ab’) fragments [3]. IVIG modulate B-cell functions with a significant reduction in serum levels of BAFF [4] and plasma cells. IVIG enhances and restores the functions of Treg cells, induces apoptosis of activated effector T lymphocytes and down regulates the production of inflammatory cytokines [3]. IVIG inhibits activation of endothelial cells, expression of adhesion molecules and secretion of soluble mediators [5]
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