High Th2 cytokine levels and upper airway inflammation in human inherited T-bet deficiency

We have described a child suffering from Mendelian susceptibility to mycobacterial disease (MSMD) due to autosomal recessive, complete T-bet deficiency, which impairs IFN-γ production by innate and innate-like adaptive, but not mycobacterial-reactive purely adaptive, lymphocytes. Here, we explore the persistent upper airway inflammation (UAI) and blood eosinophilia of this patient. Unlike wild-type (WT) T-bet, the mutant form of T-bet from this patient did not inhibit the production of Th2 cytokines, including IL-4, IL-5, IL-9, and IL-13, when overexpressed in T helper 2 (Th2) cells. Moreover, Herpesvirus saimiri–immortalized T cells from the patient produced abnormally large amounts of Th2 cytokines, and the patient had markedly high plasma IL-5 and IL-13 concentrations. Finally, the patient’s CD4⁺ αβ T cells produced most of the Th2 cytokines in response to chronic stimulation, regardless of their antigen specificities, a phenotype reversed by the expression of WT T-bet. T-bet deficiency thus underlies the excessive production of Th2 cytokines, particularly IL-5 and IL-13, by CD4⁺ αβ T cells, causing blood eosinophilia and UAI. The MSMD of this patient results from defective IFN-γ production by innate and innate-like adaptive lymphocytes, whereas the UAI and eosinophilia result from excessive Th2 cytokine production by adaptive CD4⁺ αβ T lymphocytes.     

Poor prognosis in cycles following “genuine” empty follicle syndrome

Objectives

The aim of this study was to investigate the prognosis in future IVF cycles of patients with empty follicle syndrome (EFS).

Study design

EFS cases and their future cycles were reviewed. Clinical pregnancy rate per started cycle was taken as the primary outcome in assessing the future outcome in IVF treatment cycles.

Results

A total of 3023 patients underwent 5238 IVF treatment cycles. Twenty-six patients (1%) had a total of 58 (1%) cycles of EFS. Thirteen women went through 32 further IVF treatment cycles following the diagnosis of EFS, yielding only two clinical pregnancies, giving a clinical pregnancy rate of 6.25% per started cycle. In addition, four patients had recurrence in a total of 15 cycles.

Conclusions

The occurrence of EFS will indicate poor IVF success in subsequent IVF cycles. Patients with “genuine EFS” should be counselled about the outcome of their future IVF cycles.