Differential anti-viral response to respiratory syncytial virus A in preterm and term infants.

BACKGROUND: Preterm infants are more likely to experience severe respiratory syncytial virus (RSV) disease compared to term infants. The reasons for this are multi-factorial, however their immature immune system is believed to be a major contributing factor. METHODS: We collected cord blood from 25 preterm (gestational age 30.4-34.1 weeks) and 25 term infants (gestation age 37-40 weeks) and compared the response of cord blood mononuclear cells (CBMCs) to RSVA and RSVB stimulation using neutralising assays, high-dimensional flow cytometry, multiplex cytokine assays and RNA-sequencing. FINDINGS: We found that preterm and term infants had similar maternally derived neutralising antibody titres to RSVA and RSVB. Preterm infants had significantly higher myeloid dendritic cells (mDC) RSV infection compared to term infants. Differential gene expression analysis of RSVA stimulated CBMCs revealed enrichment of genes involved in cytokine production and immune regulatory pathways involving IL-10, IL-36γ, CXCL1, CXCL2, SOCS1 and SOCS3 in term infants, while differentially expressed genes (DEGs) in preterm infants were related to cell cycle (CDK1, TTK, ESCO2, KNL1, CDC25A, MAD2L1) without associated expression of immune response genes. Furthermore, enriched genes in term infants were highly correlated suggesting an increased co-ordination of their immune response to RSVA. When comparing DEGs in preterm and term infants following RSVB stimulation, no differences in immune response genes were identified. INTERPRETATION: Overall, our data suggests that preterm infants have a more restricted immunological response to RSVA compared with term infants. While further studies are required, these findings may help to explain why preterm infants are more susceptible to severe RSV disease and identify potential therapeutic targets to protect these vulnerable infants. FUNDING: Murdoch Children's Research Institute Infection and Immunity theme grant.

TLR Responses in Preterm and Term Infant Cord Blood Mononuclear Cells.

Preterm infants are more susceptible to severe bacterial and viral infectious diseases than their full-term counterparts. A major contributor to this increased susceptibility may be due to differences in their ability to respond to pathogens. While studies have demonstrated altered bacterial Toll-like receptor (TLR) responses, there is limited data on viral TLR responses in preterm infants. In this study, cord blood mononuclear cells (CBMCs) from 10 moderately preterm (30.4-34.1 wGA), 10 term (37-39.5 wGA) infants, and 5 adults were stimulated with TLR2 (lipoteichoic acid), TLR3 (poly I:C), TLR4 (lipopolysaccharide), TLR7/8 (R848), and TLR9 (CpG-ODN 2216) agonists. Following stimulation, the cellular response was measured by intracellular flow cytometry to detect cell-specific NF-κB (as a marker of the inflammatory response), and multiplex assays were used to measure the cytokine response. This study found that preterm and term infants exhibit very similar baseline TLR expression. In response to both bacterial and viral TLR agonists comparing cell-specific NF-κB activation, preterm infants exhibited increased monocyte activation following LTA stimulation; however, no other differences were observed. Similarly, no difference in cytokine response was observed following stimulation with TLRs. However, a stronger correlation between NF-κB activation and cytokine responses was observed in term infants following poly I:C and R848 stimulation compared to preterm infants. In contrast, despite similar TLR expression, adults produced higher levels of IFN-α following R848 stimulation compared to preterm and term infants. These findings suggest preterm and term infants have a similar capacity to respond to both bacterial and viral TLR agonists. As preterm infants are more likely to develop severe infections, further research is required to determine the immunological factors that may be driving this and develop better interventions for this highly vulnerable group.

Efficacy and Safety of Methotrexate in Combination with Mini Pulse Doses of Methylprednisolone in Severe Alopecia Areata. The Vietnamese Experience.

BACKGROUND: Treatment of severe alopecia areata remains very difficult, especially in alopecia areata totalis and alopecia areata universalis. Methotrexate is known to be effective in the treatment of severe and chronic autoimmune disorders. OBJECTIVE: To assess the effectiveness and safety of MTX in combination with mini pulse dose of methylprednisolone in the treatment of severe alopecia areata. PATIENTS AND METHODS: The open, uncontrolled study compared pre-treatment and after-treatment. Thirty-eight patients (age 16-64) with severity AA (SALT score > 50 %) visiting National hospital of Dermatology and Venereology from April-2004 to September-2015 were enrolled. All patients received oral methylprednisolone 24mg/day for 3 consecutive days of a week in combination with oral MTX 7,5 mg weekly. This regimen is maintained up to 12 weeks and follow-up until to 6 months. RESULTS: After 6 months, 60.5% of patients show complete hair growth (good response) and 18.4% shows the medium response. There is a significant SALT score reduction: mean baseline SALT score 84.39 ± 17.03 compared to mean post-treatment SALT score 24.19 ± 29.42. Good clinical improvement noted in after 3 months. We do not observe any side- effects related to oral MTX and oral methylprednisolone, and no patients had to withdrawal treatment due to side- effects. CONCLUSION: Combination Methotrexate and mini pulse dose of methylprednisolone are effective and safe in treatment severity alopecia areata.

The Effectiveness of Oral Mini-Pulse Methylprednisolonein - the Treatment of Alopecia Areata in Vietnam.

BACKGROUND: Systemic corticosteroid is used to treat alopecia areata, but it is associated with side effects. Mini-pulse therapy is thought to be effective but able to reduce side effects. AIM: The study aimed to evaluate the effectiveness of oral mini-pulse methylprednisolone in the treatment of alopecia areata. METHODS: Patients received methylprednisolone 16 mg orally for 2 consecutive days every week. RESULTS: After 3 months, among patients, 40% recovered well, and 55.6% recovered fairly. After 6 months, 82.2% recovered well, 17.8% recovered fairly. No adverse events were detected, and the recurrence rate was low (2.2%). CONCLUSION: Oral mini-pulse methylprednisolone therapy is an effective and safe therapeutic option for alopecia areata without side effects, and the time of the treatment is short.