The present study evaluated the effectiveness of the Positive Parenting Program (Triple P) with a sample of Chinese parents of children with early onset conduct-related problems in Hong Kong. The participants consisted of 91 parents whose children attended maternal and child health centers and child assessment centers for service, and were between three to seven years old. Participants were randomly assigned to the intervention (TP) and a waitlist control group (WL). There was no significant difference in pre-intervention measures between the two groups. However, at post intervention, participants in the TP group reported significantly lower levels of child behavior problems, lower dysfunctional parenting styles, and higher parent sense of competence, compared to the WL group. Implications of these findings for the use of Triple P with families of Chinese descent are discussed.
This review emphasizes how translation from bench research to clinical knowledge and vice versa has resulted in considerable progress in understanding the immunopathogenesis of psoriasis. First, the journey in understanding the pathogenic mechanisms behind psoriasis is described. The roles of different components of the adaptive and innate immune systems involved in driving the inflammatory response are explained. Discovery of new immune pathways i.e. the IL23/Th17 axis and its subsequent impact on the development of novel biological therapies is highlighted. Identification of potential targets warranting further research for future therapeutic development are also discussed. Keywords psoriasis; immunopathogenesis; T cells; adaptive/innate immune responsePsoriasis is a common and stigmatising chronic inflammatory skin disease affecting about 2 % of the population worldwide 1 . This condition may cause significant morbidity due to the possible co-existence of psoriatic arthritis and association with a large number of systemic diseases 2 . A recent cohort study 3 has also shown that severe psoriasis (defined as psoriasis patients with a history of systemic therapy) is associated with an increased risk of mortality as male and female patients in the study died 3.5 and 4.4 years younger respectively than those without psoriasis (even after adjustment for classical risk factors of mortality). Hence psoriasis is a major public health problem. On an individual basis, it has a negative impact on patients' quality of life. Therefore, psoriasis poses a major social and economic burden on society. Current existing therapies only relieve symptoms but cannot cure disease. Therapeutic costs are expensive with treatments carrying substantial side effects. Therefore better understanding of the immunopathogenesis of psoriasis remains at the forefront of both basic and translational research as this is essential for the development of improved therapies. The immunological and inflammatory basis for psoriasis has been extensively reviewed in the literature 4-7 . Although considerable progress has been made in understanding the immunopathogenesis of psoriasis 1 , many fundamentally important questions regarding the functional roles of cells and molecules implicated in psoriasis remain unanswered. The aim of this review is to summarise the important findings from clinical studies and experimental models that have led to a better understanding of the immunopathogenesis of psoriasis with emphasis on how the transfer between knowledge acquired from basic research to clinical studies and vice versa is crucial for rapid progression in both areas. Important areas for future research directions will also be highlighted.
We and others have shown that the minor, nonconserved allele Gln381 of the Arg381Gln single-nucleotide polymorphism (rs11209026G>A) of the IL-23 receptor gene (IL23R) protects against psoriasis. Moreover, we have recently shown impaired IL-23-induced IL-17A production and STAT-3 phosphorylation in Th17 cells generated in vitro from healthy individuals heterozygous for the protective A allele (GA). However, the biological effect of this variant has not been determined in homozygous carriers of the protective A allele (AA), nor in psoriatic patients. Here we expand our functional investigation of the IL23R Arg381Gln gene variant to include AA homozygous individuals. By using isolated memory CD4+ T cells, we found attenuated IL-23-induced Th17 response in heterozygous individuals. Moreover, we found that AA homozygous individuals were strikingly unresponsive to IL-23, with minimal or no IL-17A and IL-17F production and failure of human memory Th17 cell survival/expansion. Finally, IL-23-induced Th17 response was also attenuated in age- and sex-matched GA versus GG psoriatic patients undergoing systemic treatment. Taken together, our data provide evidence for an allele-dosage effect for IL-23R Gln381 and indicate that common gene alleles associated with complex diseases might have biological effects of considerable magnitude in homozygous carriers.
Psoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide-range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to TNF-α (rs2524094) and IFN-γ (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-α and IFN-γ. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-α levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to up-regulation by key pro-inflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele.
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