Increased IL6 plasma levels in indolent systemic mastocytosis patients are associated with high risk of disease progression
LEUKEMIA
Authors: Mayado, A.; Teodosio, C.; Garcia-Montero, A. C.; Matito, A.; Rodriguez-Caballero, A.; Morgado, J. M.; Muniz, C.; Jara-Acevedo, M.; Alvarez-Twose, I.; Sanchez-Munoz, L.; Matarraz, S.; Caldas, C.; Munoz-Gonzalez, Ji; Escribano, L.; Orfao, A.
Abstract
Systemic mastocytosis (SM) is a heterogeneous disease with altered interleukin (IL)-6 and IL13 plasma levels. However, no study has simultaneously investigated the plasma levels of IL1 beta, IL6, IL13, CCL23 and clusterin in SM at diagnosis and correlated them with disease outcome. Here we investigated IL1 beta, IL6, IL13, CCL23 and clusterin plasma levels in 75 SM patients-66 indolent SM (ISM) and 9 aggressive SM-and analyzed their prognostic impact among ISM cases grouped according to the extent of hematopoietic involvement of the bone marrow cells by the KIT D816V mutation. Although increased IL1 beta, IL6 and CCL23 levels were detected in SM patients versus healthy controls, only IL6 and CCL23 levels gradually increased with disease severity. Moreover, increased IL6 plasma levels were associated with ISM progression to more aggressive disease, in particular among ISM patients with multilineal KIT mutation (ISM-ML), these patients also showing a higher frequency of organomegalies, versus other ISM-ML patients. Of note, all ISM patients who progressed had increased IL6 plasma levels already at diagnosis. Our results indicate that SM patients display an altered plasma cytokine profile already at diagnosis, increased IL6 plasma levels emerging as an early marker for disease progression among ISM cases, in particular among high-risk ISM patients who carry multilineage KIT mutation.
Identification of IL13 C1923T as a Single Nucleotide Polymorphism for Asthma in Children from Mauritius
PEDIATRIC ALLERGY IMMUNOLOGY AND PULMONOLOGY
Authors: Ramphul, Kamleshun; Hua, Li; Bao, Yi Xiao; Li, Jing Yang; Liu, Quan Hua; Ji, Ruo Xu; Fang, Ding Zhu
Abstract
Background: Research increasingly suggests that asthma is a familial and hereditary disorder and that genetic and environmental factors play a key role in its pathogenesis. Objective: The aim of this study was to investigate the associations between 10 single nucleotide polymorphism (SNP) loci in the development of asthma in children from the Mauritian population. Methods: The study population consisted of 193 children with asthma and 189 healthy controls from the Mauritian population. Asthma was diagnosed in accordance with the American Thoracic Society criteria. TaqMan real-time quantitative polymerase chain reaction was used to detect the genotypes of the SNP loci. Results: No statistically significant differences (p>0.05) were found between the experimental and control group in genotype distribution among nine of the loci (MS4A2 E237G, MS4A2 C-109T, ADRB2 R16G, IL4RA Q551R, IL4RA I75V, IL4 C-590T, IL13 A2044G, IL13 C-1112T, and CHI3L1 C-131G). However, the frequency of IL13 C1923T TT in the asthma group was significantly higher than in the control group (odds ratio=2.119, p=0.033) suggesting that carriers of IL13 C1923T TT in the Mauritian population may have a more significant risk of developing asthma. Conclusion: The nine loci have little contribution to the development of childhood asthma in the Mauritian population. IL13 C1923T TT has been detected to be the susceptible genotype and may have a significant effect on the pathogenesis of childhood asthma in the Mauritian population.