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Objective To explore the association of three single nucleotide polymorphisms (SNPs; rs228942, rs228941 and rs743777) in interleukin-2 receptor β subunit (IL-2Rβ) gene with the susceptibility and severity of myasthenia gravis (MG). Methods There were 480 MG patients and 487 normal controls enrolled in this study, and their three SNPs (rs228942, rs228941 and rs743777) in IL - 2Rβ gene were evaluated through SNPscanTM technique. Subgroups were classified by gender, age of onset, anti - acetylcholine receptor antibodies (AChR-Ab), thymus status, maximal involvement after 2 years of onset and maximal Oosterhuis score. Frequencies of alleles and genotypes were compared between MG group and control group, between MG subgroups and control group, and among subgroups under codominant, log - additive and overdominant models. Results The frequency of T allele of rs228942 in MG group was significantly higher than that in control group (χ2 = 4.692, P = 0.030, OR = 1.242, 95%CI: 1.021-1.511). There was significant difference in the frequency of rs228942 genotype between MG group and control group under log-additive model (P = 0.036, OR = 1.230, 95%CI: 1.010-1.480). The rs278942/rs228941 GT haplotype frequency in MG group was higher than that in control group (χ2 = 4.286, P = 0.038), while GG haplotype frequency in MG group was lower than that in control group ( χ2 = 5.333, P = 0.021). The frequencies of T allele of rs228942 was significantly higher in MG subgroups of onset age 15-50 years (χ2 = 7.474, P = 0.006, OR = 1.380, 95%CI: 1.095-1.740), non-thymoma (χ2 = 4.700, P = 0.030, OR = 1.261, 95%CI: 1.022-1.555) and maximal generalized involvement ( χ2 = 4.715, P = 0.030, OR = 1.287, 95% CI:1.025-1.617) than those in control group. Multivariate forward Logistic regression analysis found that onset age 15-50 years (OR = 9.026, 95%CI: 4.225-19.284; P = 0.000), onset age > 50 years (OR = 9.956, 95%CI:4.475-22.149; P = 0.000), thymoma (OR = 2.578, 95%CI: 1.393-4.773; P = 0.003) and positive AChR-Ab (OR = 1.946, 95%CI: 1.179-3.214; P = 0.009) were the independent risk factors for maximal involvement, while genotypes were not. Conclusions The rs228942 polymorphisms of IL-2Rβ gene may be associated with the susceptibility of MG, but not with the severity of MG. The rs228941 and rs743777 polymorphisms were not found to be associated with the susceptibility and severity of MG. DOI: 10.3969/j.issn.1672-6731.2016.10.006

Interleukin-4 (IL-4) is a potent growth and differentiation factor for B cells which play a vital role in the pathogenesis of myasthenia gravis (MG). IL-4 exerts its function by binding to three types of IL-4 receptor (IL-4R) complexes. IL-4Rα is the key component of the IL-4R complex. We hypothesize that polymorphism of IL-4Rα gene may be associated with the susceptibility and severity of MG. A Chinese cohort of 480 MG patients and 487 healthy controls were recruited. Polymorphisms of IL-4Rα gene were determined with SNPscan™ methods and compared between MG and control groups, as well as among MG subgroups. Rs2107356 and rs1805010 were found to be associated with adult thymoma associated MG, and rs1801275 was found to be associated with adult non-thymoma AChR-Ab positive MG. We did not found association between IL-4Rα polymorphism and the severity of MG. Genetic variations of IL-4Rα were found associated with the susceptibility of MG in Chinese Han population.

Sepsis is the most important predisposing cause inducing acute respiratory distress syndrome (ARDS); however, the mechanism of sepsis leading to the development of ARDS remains to be elucidated. Suppression of the mitogen-activated protein kinase (MAPK) signal by blocking the phosphorylation of Jun N-terminal kinase (JNK) and p38 in lung tissues could alleviate acute lung injury induced by sepsis. MAPK signaling may have a crucial role in development of the sepsis-induced acute lung injury. The specific inhibitors of JNK and p38 MAPK, SP600125 and SB203580, were administrated by intragastric injection 4 h before induction of ARDS after cecal ligation and puncture (CLP). Rats were sacrificed at 1, 6 or 24 h after CLP challenge. The histological evaluation, lung water content, and biochemical analysis were performed. The results revealed that the JNK and p38 MAPK inhibitor improved lung permeability, attenuated system inflammation, further alleviated the lung injury induced by sepsis. In conclusion, JNK and p38 MAPK signaling are essential for the development of ARDS following sepsis. Further studies are needed to illuminate the detailed mechanisms of JNK and p38 MAPK signaling in sepsis-induced ARDS. [ABSTRACT FROM AUTHOR]