Use of immunoglobulins in the prevention of GvHD in a xenogeneic NOD/SCID/γc− mouse model

Abstract

The efficacy of IVIG in preventing GvHD has not been definitely demonstrated clinically. Using a xenogeneic model of GvHD in NOD/SCID/ccÀ (NSG) mice, we showed that weekly administration of IVIG significantly reduced the incidence and associated mortality of GvHD to a degree similar to CsA. Unlike CsA and OKT3, IVIG were not associated with inhibition of human T-cell proliferation in mice. Instead, IVIG significantly inhibited the secretion of human IL-17, IL-2, IFN-c and IL-15 suggesting that IVIG prevented GvHD by immunomodulation. Furthermore, the pattern of modification of the human cytokine storm differed from that observed with CsA and OKT3. Finally, in a humanized mouse model of immune reconstitution, in which NSG mice were engrafted with human CD34 þ stem cells, IVIG transiently inhibited B-cell reconstitution, whereas peripheral T-cell reconstitution and thymopoiesis were unaffected. Together these in vivo data raise debate related to the appropriateness of IVIG in GvHD prophylaxis. In addition, this model provides an opportunity to further elucidate the precise mechanism(s) by which IVIG inhibit GvHD.

Anti-inflammatory IgG Production Requires Functional P1 Promoter in β-Galactoside α2,6-Sialyltransferase 1 (ST6Gal-1) Gene

“…Blood samples were taken weekly by retro-orbital bleed. For induction of acute allergic airway inflammation by ovalbumin (OVA), mice were sensitized by two intraperitoneal injections of 20 g of OVA (grade IV, Sigma) adsorbed to 2.25 mg of Imject alum (Al(OH) 3 -Mg(OH) 2 , Pierce) in 100 l of saline on days 0 and 14. Mice were challenged on days 24, 25, 26, and 27 with 20-min inhalations of an aerosol generated by nebulization of a 1% OVA solution prepared in saline.…”

Risk factors for hypogammaglobulinemia after allo-SCT

“…Ig significantly reduced the incidence and associated mortality of GVHD, a risk factor for hypogammaglobulinemia, in a mouse model. 11 Finally, our study had limitations: a heterogeneous group of patients was assessed and it was a retrospective single-center study over a long time period. Large-scale prospective studies are needed to substantiate the results of this retrospective analysis.…”

Circulating Myeloid Dendritic Cells is Decreased in the Acute Phase of Kawasaki Disease

“…Regular immunoglobulin treatment is reported to be effective in experimental model of graft-versus-host disease [30] in which pathophysiological involvement of DCs is postulated and the reduced number of DCs is documented.…”