Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.
Recent advancements in immunosuppression and surgical techniques have significantly improved the outcome of kidney transplantation in the pediatric population. Adolescents enjoy the best 1-year graft survival of any age group. However, the long-term transplant outcome in adolescents is disappointing. Non-adherence with immunosuppressive medications is one of the most important contributing factors for graft rejection and loss in teenagers. The impact of non-adherence is perceived to be far more powerful in adolescent transplant recipients than in the transplant population as a whole. To better understand adolescent non-adherence, the process of transplantation must be placed in the context of adolescent development. Adolescents try to establish their identity and autonomy separately from the parents; however at the same time, adolescents with chronic illness require help, support and guidance from adults, including parents and medical personnel. Adolescents have limited ability to anticipate abstractly the long-term consequences of their immediate actions. This inconsistency can create frustration in both adolescents and in the supporting systems around them. Despite the significant consequences of adolescent non-adherence, research in this area is scarce. There are still no established definitions, standardized diagnostic methods and effective interventions to treat and prevent this problem. We propose the recommendations to approach the problems of adolescent transplant non-adherence from the transplant clinician's viewpoint. With early identification and appropriate interventions, significant improvement in adolescent graft survival is possible.
The novel CHIKV mutation could potentially modify the epidemiological presentation of CHIK fever. Early diagnosis of CHIK fever is essential for preventing further massive outbreaks.
This study shows a significant 4.5-fold risk of graft failure at two years postbiopsy with presence of > or =2 CD20+ cells/hpf. Moreover, > or =3 CD20+ lymphocytes were highly associated with acute cellular rejection. They may be functioning as professional antigen-presenting cells in the graft. In steroid-refractory cellular rejections, therapies that target B cells may prolong graft survival.
Advances in knowledge in transplantation have improved 1-year renal allograft survival in all age groups of pediatric patients. However, the results from many studies have shown that the long-term allograft survival is least successful in adolescent recipients. The major cause of late graft failure in adolescents can be contributed in large measure to medication noncompliance. Medication noncompliance in teenagers has been shown to be more than four times greater in adolescents than in adults. The teenage years are a time of transition from childhood to adulthood. Important tasks during this transition include the development of an autonomous identity that progresses to full independence. However, the cognitive skills and intellectual maturation of adolescents are still limited, and this is particularly true in adolescents with chronic diseases. They have difficulty with abstract thinking, particularly the conceptualization of future consequences of present actions. This leads to characteristic risk-taking behaviors, including noncompliance with medical treatments. This transition is more intricate for adolescents with chronic illness because of their physical limitations. There are a number of strategies that are helpful in mitigating noncompliance. Adolescents must be dealt with directly. Previous noncompliant behaviors need to be acknowledged and dealt with, because studies show that noncompliance is a "stable" personality attribute that persists over time. Efforts should be made to choose medications that have the least side effects. Psychological and psychiatric conditions such as posttraumatic stress disorder require early recognition, diagnosis, and treatment. It is necessary to build rapport with teenagers, and this should start before transplantation. A multidisciplinary approach with physicians, social workers, nurses, and transplant coordinators is an effective mean of enhancing compliance. These and other strategies outlined in this discussion will enable the adolescent to achieve good compliance rates and prevent graft loss.
Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic involvement. The susceptibility genes identified so far can only explain a small proportion of disease heritability. Through a genome-wide association in a Hong Kong Chinese cohort and subsequent replication in two other Asian populations, with a total of 3164 patients and 4482 matched controls, we identified association of ELF1 (E74-like factor 1) with SLE (rs7329174, OR = 1.26, joint P= 1.47 × 10(-8)). ELF1 belongs to the ETS family of transcription factors and is known to be involved in T cell development and function. Database analysis revealed transcripts making use of three alternative exon1s for this gene. Near equivalent expression levels of distinct transcripts initiated from alternative exon1s were detected in peripheral blood mononuclear cells from both SLE patients and healthy controls. Although a direct association of rs7329174 with the three forms of transcripts for this gene was not detected, these findings support an important role of ELF1 in SLE susceptibility and suggest a potentially tight regulation for the expression of this gene.
Chikungunya virus infection has recently emerged in several countries. The inflammatory response is suggested to be involved in the pathology observed in this infectious disease. Interleukin-18 (IL-18) is an inducer of interferon-gamma (IFN-gamma) production and has been shown to play a role in several inflammatory diseases. IL-18 binding protein (IL-18BP) is a natural regulator of IL-18. In this study, we determined the levels of IL-18 and IL-18BP in patients with Chikungunya virus infection. Acute and convalescent sera were collected from each patient. The levels of both IL-18 and IL-18BP were measured by ELISA assays. IL-18 and IL-18BP levels were higher in patients than in controls. In addition, the level of IL-18 was higher in convalescent than in acute sera. However, the level of IL-18BP was lower in convalescent than in acute sera. These data suggest that production of both IL-18 and IL-18BP was induced following Chikungunya virus infection. IL-18BP was increased to regulate the activity of IL-18. The ratio of IL-18 to IL-18BP was higher in convalescent than in acute sera. The lower level of IL-18BP in convalescent sera was probably due to loss following IL-18 neutralization. Our data suggest that Chikungunya virus infection promotes the T helper-1 (Th-1) response by inducing IL-18 production. Manipulation of IL-18 and IL-18BP levels could be a promising therapeutic approach to alleviate symptoms in patients with Chikungunya virus infection.
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