Polyclonal, newly derived T cells with low expression of inhibitory molecule PD-1 in tonsils define the phenotype of lymphocytes in children with Periodic Fever, Aphtous Stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome.

PURPOSE: PFAPA syndrome is a benign, recurrent inflammatory disease of childhood. Tonsillectomy is one of the therapeutic options with a yet unexplained biological mechanism. We tested whether specific lymphocyte subsets recruited from blood to human tonsils participate in PFAPA pathogenesis. METHODS: Paired tonsils/peripheral blood (PB) samples were investigated (a) from children with PFAPA that successfully resolved after tonsillectomy (n=10) (b) from children with obstructive sleep apnoea syndrome as controls (n=10). The lymphocyte profiles were analysed using 8-colour flow cytometry, immunoglobulin (IGH) and T-cell receptor (TCR) gene rearrangements via PCR and next generation sequencing; a TREC/KREC analysis was performed using qPCR. RESULTS: The PFAPA tonsils in the asymptomatic phase had a lower percentage of B-lymphocytes than controls; T-lymphocyte counts were significantly higher in PB. The percentages of cytotoxic CD8pos T-lymphocytes were approximately 2-fold higher in PFAPA tonsils; the transitional B cells and naïve stages of both the CD4pos and CD8pos T-lymphocytes with a low expression of PD-1 molecule and high numbers of TREC were also increased. With the exception of elevated plasmablasts, no other differences were significant in PB. The expression levels of CXCL10, CXCL9 and CCL19 genes were significantly higher in PFAPA tonsils. The IGH/TCR pattern showed no clonal/oligoclonal expansion. DNA from the Epstein-Barr virus, Human Herpervirus-6 or adenovirus was detected in 7 of 10 PFAPA tonsils but also in 7 of 9 controls. CONCLUSIONS: Our findings suggest that the uninhibited, polyclonal response of newly derived lymphocytes participate in the pathogenesis of PFAPA. Because most of the observed changes were restricted to tonsils and were not present in PB, they partly explain the therapeutic success of tonsillectomy in PFAPA syndrome.

Successful early neonatal repair of cleft lip within first 8 days of life.

OBJECTIVE: In the children born with a cleft lip, surgery is the first step in correcting the inborn anomaly. In comparison with usually made 3-month surgery, benefits of the surgery in neonates have been reported: a very good wound healing, feeding facilitation, and good socialization of a child from neonatal age. The aims of the present study were to perform cheiloplasty in early newborns affected by the total cleft lip and palate (CLP) by the technique modified to search for optimum aesthetic result, and to assess the surgery outcome from qualitative and quantitative aspects. METHODS: The operations were performed by the same surgeon in 97 neonates 1-8 days old during 2005-2008. The original technique by Tennison was modified and used. Aesthetic outcome of the surgery was evaluated according to scar visibility, and the shape and symmetry of the lip and nose. The effect of cheiloplasty on the formation of the upper jaw segments was evaluated in a sample of unilateral CLP patients using the 3D-finite element scaling analysis (FESA). We compared 3D models of dental plaster casts made prior to lip surgery (in neonates under 8 days of age) and prior to palate surgery (at 12 months of age). RESULTS: Only the children in excellent health state and without an associated inborn defect were allowed to pass the operation. There were no per-operative complications (except the correction of tracheal tube position in several cases). The parents appreciated bringing home a neonate with no visible cleft. This aspect not only facilitated baby feeding, but had important positive psycho-social impact on the whole family. The wound healing and aesthetic effect of the cheiloplasty were very good. The scar was barely visible and lip and nose were symmetric in majority of children. After lip closure, the growth and approximation of jaw segments was observed. This aspect was also associated with incisors development in the anterior portion of the segment including premaxilla. CONCLUSIONS: Our results show, that early neonatal lip surgery of CLP is promising technique with very good aesthetic results and important positive psychological impact on the child and its family.