CD25 appears non essential for human peripheral T(reg) maintenance in vivo.

BACKGROUND: IL-2 has been reported to be critical for peripheral T(reg) survival in mouse models. Here, we examined T(reg) maintenance in a series of paediatric liver transplant recipients who received basiliximab, a therapeutic anti-CD25 monoclonal antibody. METHODOLOGY/PRINCIPAL FINDINGS: FoxP3+ CD4 T cells were analyzed by flow cytometry before liver grafting and more than 9 months later. We found that in vivo CD25 blockade did not lead to T(reg) depletion: the proportion of FoxP3+ cells among CD4 T cells and the level of FoxP3 expression were both unchanged. IL-2Rbeta expression was enhanced in FoxP3+ cells both before and after basiliximab treatment, while the level of IL-2Rgamma expression was similar in T(regs) and non-T(regs). No significant change in the weak or absent expression of IL-7Ralpha and IL-15Ralpha expression on FoxP3+ cells was observed. Although the proportion of FoxP3+ cells among CD4 T cells did not vary, food allergies occurred more rapidly after liver grafting in patients who received basiliximab, raising questions as to T(reg) functionality in vivo in the absence of functional CD25. CONCLUSIONS: CD25 appears non essential for human T(reg) peripheral maintenance in vivo. However, our results raise questions as to T(reg) functionality after therapeutic CD25 targeting.

AIRE gene analysis in children with autoimmune hepatitis type I or II.

The present report describes AIRE gene analysis in 25 children with autoimmune hepatitis type I or II. The heterozygous transversion c.961C > G (p.Ser278Arg) located in exon 7 was identified in 4 patients with autoimmune hepatitis type I, and mostly in those presenting with a positive family history for autoimmune diseases. In this subgroup of patients, the allelic frequency of this polymorphic variant was at least 3-fold higher than in healthy controls. These results suggest that heterozygous AIRE gene mutation may represent a genetic predisposition to childhood autoimmune hepatitis type I.

Aspergillus fumigatus endocarditis in a pediatric liver transplant recipient: favorable outcome without cardiac surgery.

Transplant recipients are very susceptible to invasive aspergillosis, which increases mortality rate. Disseminated aspergillosis in the liver transplant recipient can affect virtually any organ and endocarditis is often lethal despite cardiac surgery and antifungal therapy. We report the case of a eight-month-old girl who presented with Aspergillus fumigatus endocarditis 18 days after liver transplantation that was successfully treated by a combination of antifungal drugs associated to a low dosage of immunosuppressive therapy.

Acute renal failure in a 3-year-old child as part of the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome following hepatitis A.

We report on a 3-year-old Melanesian girl admitted for acute renal failure following subfulminant hepatitis A virus infection. While the child was slowly recovering from severe cytolytic hepatitis, she presented 8 weeks of protracted fever and major eosinophilia (30,000/microl); thereafter, acute renal failure (serum creatinine 295 micromol/l) occurred. Renal histology displayed diffuse eosinophilic infiltrate, with severe acute tubulointerstitial lesions associated with mild glomerular endocapillary proliferation and eosinophilic infiltrate, suggesting an immunoallergic mechanism. The child had received cefixime and cotrimoxazole 3 weeks prior to hospitalisation for the hepatitis A virus infection. The final diagnosis was of the syndrome drug reaction with eosinophilia and systemic symptoms or DRESS, induced by cefixime or cotrimoxazole and possibly triggered by the hepatitis A virus infection.