Prevalence of congenital cryptorchidism in Estonia.

BACKGROUND: Cryptorchidism is one of the most common urogenital malformations. Cryptorchidism prevalence varies greatly in different countries and populations. The aim of the current study was to determine and analyse cryptorchidism prevalence in Estonia. MATERIALS AND METHODS: During 2012-2015, all consecutively born 5014 boys at Tartu University Hospital were examined for cryptorchidism. All the subjects with cryptorchidism were followed up for at least 6 months to assess spontaneous testicular descent. RESULTS: Note that 2.1% cases had one or both testicles undescended at birth, 1.6% cases at expected date of birth, 1% cases at 3 months of age, and 0.8% cases at the age of 6 months had cryptorchidism. Cryptorchidism prevalence at birth was higher in preterm boys (11.9%), boys of low birth weight (16.7%) and boys small for gestational age (14%) but was lower in full-term newborn boys (1.1%). During follow-up, testes descended spontaneously in 61.6% of boys, more commonly in prematurely born boys (92%) and boys with low gestational weight (93%) as compared to full-term cryptorchid boys (29.2%) and cryptorchid boys with normal birth weight (34%). At the age of 6 months, cryptorchidism prevalence was equalized in preterm boys (0.9%) and boys with low birth weight (1%) as compared to full-term boys (0.7%) and boys with normal birth weight (0.7%). Boys SGA required surgical intervention more commonly than boys with normal birth weight. Ethnically, cryptorchidism prevalence at birth was similar among Estonians and non-Estonians. CONCLUSION: Our data revealed that cryptorchidism prevalence, especially in full-term boys, is lower in Estonia than reported in the other Nordic-Baltic countries and worldwide.

Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.

The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th1) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1ß (but not IL-6 or tumor necrosis factor [TNF]-α), Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

Expression of B7 and CD28 family genes in newly diagnosed type 1 diabetes.

Type-1 diabetes (T1D) is caused by T-cell mediated autoimmune reaction directed against the insulin-secreting beta cells. We hypothesized that in addition to antigen/MHC recognition the co-stimulatory B7 and CD28 pathway is also strongly affected in T1D. CD80, CD86, CD28, CTLA4, ICOS and CD25 mRNA expression was characterized in 49 newly diagnosed young T1D patients (mean age 11 ± 5 years, 25 male/24 women) and 31 controls (mean age 14 ± 7 years, 14 male/17 women). In addition, polymorphisms in CTLA4 (rs231806, rs231775, rs3087243) were genotyped and soluble CTLA4 plasma levels measured by ELISA. T1D patients presented with higher peripheral blood expression levels of CD80 (Mann-Whitney U-test, p=0.0001) and lower ICOS levels compared to healthy controls (Glm adjusted for age, p=0.0004). CD80 expression in T1D patients correlated with expression of two CTLA4 splice variants (Spearman's rank correlation, rho=0.56, p=0.0002 for sCTLA4; rho=0.61, p<0.0001 for flCTLA4). In controls, CD80 expression correlated with CD25 expression (Spearman's rank correlation, rho=0.57, p=0.002). A strong correlation was observed between sCTLA4 and flCTLA4 (Spearman's rank correlation, rho=0.94, p<0.0001). We also found a tendency that the CTLA4 +49A/G polymorphism influenced sCTLA4 mRNA expression in T1D individuals and was lowest in individuals with the GG genotype (Mann-Whitney U-test, p=0.039). However, we could not identify associations between gene expression and plasma levels of sCTLA4. To summarize, we expect that newly diagnosed T1D among children and adolescents is associated with activation of CD80 and CTLA4 in peripheral blood. Additional studies will be needed to elucidate the role of CD80/CTLA4 signaling in T1D.