Expression of the miR-9-5p, miR-125b-5p and its target gene NFKB1 and TRAF6 in childhood-onset systemic lupus erythematosus (cSLE).

Childhood- onset systemic lupus erythematosus (cSLE) is a multisystem inflammatory disease that can lead to severe clinical conditions resulting in early comorbidities. Several genetic, environmental, and immunological factors are known to influence the onset of the disease. MiRNAs have been already considered as potential actors involved in the development and activity of the SLE. Thus, understanding the behavior of these regulators can contribute to clarify the inflammatory process affecting SLE patients. Among miRNAs, miR-125b-5p and miR-9-5p targeting NFKB1 and TRAF6 genes can be involved in the etio-pathogenesis of the disease by modulating inflammation. In this study we evaluated miR-9-5p and miR-125b-5p expression and its target genes NFKB1 and TRAF6 in peripheral blood samples (PBMC) from the 35 cSLE patients and 35 healthy controls. MiRNAs and gene target expression have been evaluated by using RT-PCR with specific TaqMan® probes. Both miR-9-5p [Fold Change (FC) = -2.21; p = 0.002] and miR-125b-5p (FC= -3.30; p < 0.0001) and NFKB1 (FC = -1.84; p < 0.001) were downregulated in cSLE patients, while TRAF6 was upregulated (FC = 1.80; p = 0.006) in cSLE patients when compared to controls. A significant correlation was found between miR-125b-5p and its target gene NFKB1 [Spearman (r) = 0.47; p = 0.023]. Our results showed miR-125b-5p and miR-9-5p differential expression in cSLE patients, possibly contributing to better understanding the role of these regulators in cSLE development and disease pathogenesis.

Efficacy of Probiotics in Children and Adolescents With Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Study.

OBJECTIVE: To evaluate the clinical efficacy of a mixture of probiotics (Lactobacillus and Bifidobacterium) in children and adolescents with atopic dermatitis (AD) and the effects on sensitization, inflammation, and immunological tolerance. METHODS: In this double-blind, randomized, placebo-controlled clinical trial, we enrolled 60 patients aged between 6 months and 19 years with mild, moderate, or severe AD, according to the criteria proposed by Hanifin and Rajka. Patients were stratified to receive one gram per day of probiotics or placebo for 6 months. The primary outcome was a decrease in SCORing Atopic Dermatitis (SCORAD). Secondary outcomes were to assess the role of probiotics on the use of topical and oral medicines (standard treatment), serum IgE levels, skin prick test (SPT), and tolerogenic and inflammatory cytokines. Background therapy was maintained. RESULTS: Forty patients completed the study (24 probiotics, 16 placebo). After treatment for six months, the clinical response was significantly better in the probiotics group; the SCORAD decreased [mean difference (MD) 27.69 percentage points; 95% confidence interval (CI), 2.44-52.94], even after adjustment for co-variables (MD 32.33 percentage points; 95%CI, 5.52-59.13), especially from the third month of treatment on. The reduction of the SCORAD in probiotic group persisted for three more months after the treatment had been discontinued, even after adjustment for co-variables (MD 14.24 percentage points; 95%CI, 0.78-27.70). Patients in the probiotics group required topical immunosuppressant less frequently at 6 and 9 months. No significant changes were found for IgE levels, SPT and cytokines. CONCLUSIONS: Children and adolescents with AD presented a significant clinical response after 6 months with a mixture of probiotics (Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus paracasei, and Bifidobacterium lactis. However, this clinical benefit is related to treatment duration. Probiotics should be considered as an adjuvant treatment for AD.

Higher interferon score and normal complement levels may identify a distinct clinical subset in children with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex multi-system disease, characterized by both autoimmune and autoinflammatory clinical and laboratory features. The role of type I interferon (IFN) in SLE has been demonstrated from the 2000s, by gene expression analyses showing significant over-expression of genes related to type I IFN signalling pathway (IFN signature). However, several studies questioned the role of measuring the intensity of IFN signature (IFN score) to chase SLE activity. We would assess if the IFN signature can help the clinical and therapeutic stratification of patients with pediatric SLE. METHODS: We measured the IFN score in peripheral whole blood from a series of subjects with childhood-onset SLE and correlated the results with clinical and laboratory parameters. RESULTS: Thirty-one subjects were included in the study, among which the 87% displayed a positive IFN score. The only significant relation was found for high IFN score in subjects with normocomplementemia. No correlation was observed between IFN score and SLEDAI-2K, BILAG-2004 and SLICC. Patients with high IFN score and normal complement levels also presented lower anti-dsDNA antibodies. CONCLUSIONS: The integration between IFN signature analysis and complement levels may easily distinguish two groups of subjects, in which the autoimmune or autoinflammatory component of the disease seems to be prevalent.

Salivary antibody response to streptococci in preterm and fullterm children: a prospective study.

OBJECTIVES: Secretory immunoglobulins present in mucosa surfaces represent the first line of defense of the adaptive immune system against infectious challenges. Preterm (PT) neonates' humoral immunity is diminished compared to full-term (FT) newborns. The identification of important antigens (Ags) of virulence of oral species may help in the investigation of the mechanisms of antigenic stimulation and the development of the mucosal immune response. In the present study, we measured saliva levels of immunoglobulins A (IgA) and M (IgM) and characterized the specificity of IgA against Ags of several streptococcal species found early in life. METHODS: This was a prospective observational study. Salivary IgA (sIgA) antibody responses to bacterial species that are prototypes of pioneer (Streptococcus mitis, S. sanguinis, S. gordonii) and pathogenic (Streptococcus mutans) microorganisms of the oral cavity were studied in FT and PT children in two visits: at birth (T0) and at 3 months of age (T3). Salivas from 123 infants (72 FT and 51 PT) were collected during the first 10h after birth (T0) and again at 3 months of age (T3). Salivary levels of IgA and IgM antibodies were analysed by enzyme-linked immunosorbent assay (ELISA). A subgroup of 26 FT and 24 PT children were compared with respect to patterns of antibody specificities against different streptococci Ags using Western blot assays. RESULTS: No significant differences (P>0.05) in salivary levels of IgA and IgM between FT and PT babies were found at birth. At T3, mean sIgA values were similar between groups and sIgM levels were significantly higher in PT than FT (P<0.05). Western blot assays identified positive IgA response to streptococci in the majority of children, especially in the FT group. There were some differences between groups in relation to the frequency of children with positive response to Ags and intensity of IgA response. In general, oral streptococci Ags were more frequently detected and bands were more intense in FT than in PT, especially in T3. Prospective analysis of patterns of sIgA against Ags of different streptococcal species revealed an increase in complexity of the sIgA antibody response from the first day of birth (T0) to T3 in PT and FT. CONCLUSION: The patterns of sIgA response to streptococci Ags appear to be influenced by the gestational age, which might reflect the level of immunological maturity of the mucosal immune system.