Recognition of heat shock protein 60 epitopes in children with type 1 diabetes.

BACKGROUND: Treatment with a specific HSP60 epitope in new onset of type 1 diabetes (T1D) patients has been shown to preserve endogenous insulin production. Previously, recognition of pan HLA-DR-binding HSP60 epitopes in various autoimmune diseases was found; this study investigated recognition of these epitopes in newly diagnosed T1D patients and correlated findings to the occurrence of a partial remission. METHODS: Peripheral blood mononuclear cells of 18 children with T1D were prospectively collected at disease onset and a few months after diagnosis. Epitope-specific T-cell proliferation and cytokine production (intracellular and in culture supernatants) were measured. Results were compared with 31 longstanding T1D patients and ten healthy controls. RESULTS: Although HSP60 epitope-specific T-cell proliferative responses were detected, overall proliferative responses were low. At onset, epitope-specific intracellular IFN-γ production was higher in T1D patients compared with healthy controls (p < 0.05). At follow-up, both IL-10 and IFN-γ production were higher in those without a partial remission than in those with a partial remission (both p < 0.05). Also, IL-10 and IFN-γ production were higher compared with onset for patients without a PR (both p < 0.01). In supernatants of HSP60 epitope-specific T-cell cultures, no substantial differences in cytokine production were found between T1D patients with and without a partial remission, either at onset or a few months after onset. As patient numbers were small, results should be interpreted with caution. CONCLUSIONS: Pan-DR-binding HSP60 peptides induced low peptide-specific proliferative responses and peptide-specific production of some, mainly intracellular, cytokines in T1D patients. Recognition did not differ significantly between patient groups and various time points.

[From gene to disease; congenital adrenal hypoplasia and the DAX-1 gene]. / Van gen naar ziekte; congenitale bijnierschorshypoplasie en het DAX-1-gen.

Congenital adrenal hypoplasia is an X-linked disorder resulting in adrenocortical deficiency, failure to complete puberty due to hypogonadotrophic hypogonadism, and infertility. The disease is caused by mutations in the DAX-1 gene. The DAX-1 protein is a transcription inhibitor; it represses the transcription of other, as yet mostly unknown, genes. Mutation analysis can confirm a clinical diagnosis of congenital adrenal hypoplasia. An early diagnosis might prevent critical damage due to an adrenal crisis in an undiagnosed patient. Molecular testing can be used for carrier detection and genetic counselling.

[When is a tall child too tall?]. / Wanneer zijn lange kinderen te lang?

3 children presented with tall stature. A 14-year-old girl of 179.6 cm was found to be within her target height range and was treated with oestrogen. A 15.5-year-old boy of 199,5 cm was beyond his target height range and was found to have a 47,XYY karyo- type; growth was inhibited with epiphysiodesis. A 12-year-old girl of 178.5 cm and very long legs was beyond her target height range but was found to have homocysteinaemia, a contraindication for hormonal- growth inhibition. her final height was 192 cm. Children growing above the 98th percentile of the growth curve are considered too tall. Most children with tall stature are constitutionally tall and remain within their target height range; no additional investigation is needed. In contrast, growth above this range or disproportionate growth and/or the presence of dysmorphic features in the child or parents warrants further investigation and may reveal important diagnoses. Height prediction based on bone age reading plays a key role in the management of tall children. Treatment with sex steroids may be used in an attempt to limit final height, but some conditions underlying tall stature are a contraindication for this treatment.