An association between the PARK16 locus and Parkinson's disease in a cohort from eastern China.

Genome-wide association studies (GWAS) have identified several single-nucleotide polymorphisms (SNPs) at the PARK16 locus that can modulate the risk of Parkinson's disease (PD), including rs16856139, rs823128, rs823122, rs947211, rs823156, rs708730 and rs11240572. The strength of these associations has been investigated in people from several ethnic origins, including Europe, Chile, Japan, Taiwan and western China. The results have shown that an ethnicity-specific effect is an important consideration in such an analysis. Therefore, we genotyped the above seven SNPs using a case-control methodology to explore their association with the risk of PD in eastern China. A total of 456 study subjects comprising 226 patients with PD and 230 unrelated healthy controls were recruited. The minor allele frequencies at the rs16856139 and rs11240572 SNPs were found to be significantly higher in controls than in PD cases, which suggested that they conferred a protective effect against PD. Further analyses from more diverse ethnic origins are required to confirm the significance of rs16856139 and rs11240572.

Novel mutations of the SPG11 gene in hereditary spastic paraplegia with thin corpus callosum.

BACKGROUND: Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a clinically and genetically heterogeneous neurodegenerative disorder with genetic linkage to multi-loci. Recently pathogenic mutations in the KIAA1840 (now named SPG11) for SPG11, the major HSP-TCC locus, were identified; at least 42 different mutations have been detected. OBJECTIVE: To study the clinical features and identify the SPG11 gene mutations in Chinese patients with HSP-TCC. METHODS: Three kindreds with an autosomal recessive HSP-TCC and 5 cases with sporadic HSP-TCC in Chinese Hans were recruited. Detailed clinical history, neurological examination, MRI, electromyography, Mini Mental State Examination (MMSE), Spastic Paraplegia Rating Scale (SPRS) were presented. DNA samples of the 8 families were collected and mutation analysis of SPG11 gene was carried out by direct DNA sequencing. RESULTS: Except for one patient whose age at onset was 3 years old, 10 patients manifested a relatively similar combination of adolescence-onset cognitive decline and spastic paraparesis with TCC on brain MRI. We identified 10 novel and one known mutations in our 8 HSP-TCC families, which were two nonsense mutations (c.5977C>T/p.Q1993X, c.4668T>A/p.Y1556X), three small deletions (c.6898_6899delCT/p.L2300AfsX2338, c.3719_3720delTA/p.I1240VfsX263, c.733_734delAT/p.M245VfsX246), four small insertions (c.7088_7089insATTA/p.Y2363X, c.2163_2164insT/p.I722YfsX731, c.7101_7102insT/p.K2368X, c.6790_6791insC/p.L2264PfsX2339), one deletion/insertion (c.654_655delinsG/p.S218RfsX219), and one splice mutation (c.7151+4_7151+7delAGTA/p.K2384fsX2386). Each family has a different mutation and all the mutations are predicted to cause early protein truncation. CONCLUSION: This study widens the mutation spectrum of the SPG11 gene and the mutations in the SPG11 gene are also the major causative gene for HSP-TCC in the Chinese Hans. Screening of the whole gene is recommended in clinical practice.

Soluble CTLA-4 in sera of patients with bronchial asthma.

Cytotoxic lymphocyte associated antigen-4 (CTLA-4) is a homologue of CD28, which plays a critical role in the down-regulation of antigen-activated immune response. The aim of the present study was to investigate the concentrations of soluble CTLA-4 in sera of patients with bronchial asthma and the correlation between soluble CTLA-4 concentrations and some clinical measures of asthma. The concentrations of serum soluble CTLA-4 in 31 atopic asthmatics, 20 non-atopic asthmatics, and 28 non-atopic normal control volunteers were determined by ELISA technique, and the relationship between serum soluble CTLA-4 concentrations in asthmatics and airway responsiveness, pulmonary function, blood white cell counts and differentials, respectively, were analyzed. Serum soluble CTLA-4 concentrations in both atopic asthmatics (20.2 +/- 5.4 microg/L) and non-atopic asthmatics (19.2 +/- 6.2 microg/L) were all higher than that in normal controls (1.8 +/- 0.8 microg/L, p = 0.04 and 0.014, respectively). There was no difference in serum soluble CTLA-4 concentrations between atopic and non-atopic asthmatics (p = 0.877). The serum soluble CTLA-4 concentrations in the asthmatics statistically correlated with forced expiratory volume in one second (r = -0.410, p = 0.027), percentage of predicted peak expiratory flow (r = -0.449, p = 0.015), and PaCO2 (r = 0.555, p = 0.002), respectively. Our data also showed that the concentration of soluble CTLA-4 was significantly related to blood lymphocyte numbers. The serum soluble CTLA-4 protein level was significantly elevated in patients with asthma. This level correlated with the severity of asthma. Our data also showed that the concentration of soluble CTLA-4 was significantly related to blood lymphocyte numbers.

[Endobronchial eosinophils preferentially stimulate T helper cell type 2 responses].

OBJECTIVE: The aim of the present study was to evaluate whether eosinophils within the tracheobronchial lumen can stimulate Th2 cell expansion by presenting antigen both in vitro and in vivo. METHODS: Airway eosinophils were recovered from ovalbumin-sensitized and -challenged BALB/c mice, these eosinophils were then cocultured with sensitized CD4(+) cells in the absence or presence of anti-CD80 or/and -CD86 monoclonal antibodies. Airway eosinophils were instilled into the trachea of sensitized mice, At 3 d thereafter, the draining paratracheal lymph nodes were removed and teased into cell suspensions for culture. Cell-free culture supernatants were collected for detection of cytokines. RESULTS: Our data showed that airway eosinophils, recovered following inhalational ovalbumin challenge in sensitized mice functioned as CD80- and CD86-dependent antigen-presenting cells to stimulate sensitized CD4(+) lymphocytes to produce IL-4, IL-5 and IL-13, but not interferon-gamma (IFN-gamma) in vitro assay. When instilled intratracheally in ovalbumin-sensitized recipient mice, these antigen-loaded eosinophils migrated into draining paratracheal lymph nodes primed Th2 cells in vivo for IL-4, IL-5 and IL-13, but not IFN-gamma, production during the in vitro culture that was also CD80- and CD86-dependent. CONCLUSIONS: We concluded that eosinophils within the lumina of airways could process inhaled antigen function in vitro and in vivo as antigen-presenting cells to promote expansion of Th2 cells. This investigation highlights the potential of eosinophils to not only act as terminal effector cells but also to actively modulate immune responses by amplifying Th2 cell responses.