[Clinical effect of tacrolimus in the treatment of myasthenia gravis in children].

OBJECTIVE: To evaluate the efficacy and safety of tacrolimus in the treatment of children with myasthenia gravis (MG). METHODS: A total of 28 children with MG were treated with tacrolimus. MG-Activities of Daily Living (MG-ADL) scale was used to assess clinical outcome and safety after 1, 3, 6, 9, and 12 months of treatment. RESULTS: After tacrolimus treatment, the MG-ADL score at 1, 3, 6, 9 and 12 months was lower than that at baseline (P<0.05), and the MG-ADL score showed a gradually decreasing trend. The response rates to tacrolimus treatment at 1, 3, 6, 9, and 12 months were 59%, 81%, 84%, 88%, and 88% respectively. At 6, 9, 12, and 18 months of treatment, 4, 13, 14, and 15 children respectively were withdrawn from prednisone. No recurrence was observed during treatment. Major adverse reactions/events were asymptomatic reduction in blood magnesium in 5 children and positive urine occult blood in 1 child, which turned negative without special treatment, and tacrolimus was not stopped due to such adverse reactions/events. One child was withdrawn from tacrolimus due to recurrent vomiting. According to CYP3A5 genotypes, all of the patients were divided into two groups: slow metabolic type (n=19) and non-slow metabolic type (fast metabolic type + intermediate type; n=9). The non-slow metabolism group received a higher dose of tacrolimus, but had a lower trough concentration of tacrolimus than the slow metabolism group (P<0.05). The slow metabolism group had a higher response rates to tacrolimus treatment than the non-slow metabolism group (P<0.05). CONCLUSIONS: Tacrolimus appears to be effective and safe in the treatment of children with MG and is thus an option for immunosuppressive therapy. CYP3A5 genotyping has a certain guiding significance for determining the dosage of tacrolimus.

[Association of IL-1ß-511T gene rs16944 polymorphism with febrile seizures].

OBJECTIVE: Despite substantial research efforts worldwide, the role of inflammatory cytokine IL-1ß in the onset of febrile seizures (FS) remains controversial. The aim of this study was to assess the relationship between rs16944 polymorphism of the IL-1ß-511T gene and occurrence of simple FS in a sample of Han children in northern China. METHODS: The IL-1ß-511T gene rs16944 was genotyped by SNaPshot SNP technique in 141 FS children and 130 healthy control subjects. The genotypic and allelic frequencies in the two groups were comparatively analyzed. RESULTS: There were no significant differences in genotypic and allelic frequencies of rs16944 polymorphism of the IL-1ß-511T gene between FS patients and control subjects (P>0.05).When the clinical data on A/A, A/G and G/G genotypes of the rs16944 polymorphism in FS patients, there was statistically significant difference in age of first onset (χ(2)=19.491, P<0.01), temperature of first onset (χ(2)=9.317, P<0.05) and family history of FS (χ(2)=26.798, P<0.01). CONCLUSIONS: There is no association between rs16944 polymorphism of the IL-1ß-511T gene and the incidence of FS in Han children in Northern China. However, the differences in genotypes of this polymorphism might be associated with pathogenesis and prognosis of simple FS in the population studied.

Next-Generation Sequencing Analysis Reveals Novel Pathogenic Variants in Four Chinese Siblings With Late-Infantile Neuronal Ceroid Lipofuscinosis.

Neuronal Ceroid Lipofuscinoses (NCLs) are progressive degenerative diseases mainly affect brain and retina. They are characterized by accumulation of autofluorescent storage material, mitochondrial ATPase subunit C, or sphingolipid activator proteins A and D in lysosomes of most cells. Heterogenous storage material in NCLs is not completely disease-specific. Most of CLN proteins and their natural substrates are not well-characterized. Studies have suggested variants of Late-Infantile NCLs (LINCLs) include the major type CLN2 and minor types CLN5, CLN6, CLN7, and CLN8. Therefore, combination of clinical and molecular analysis has become a more effective diagnosis method. We studied 4 late-infantile NCL siblings characterized by seizures, ataxia as early symptoms, followed by progressive regression in intelligence and behavior, but mutations are located in different genes. Symptoms and progression of 4 types of LINCLs are compared. Pathology of LINCLs is also discussed. We performed Nest-Generation Sequencing on these phenotypically similar families. Three novel variants c.1551+1insTGAT in TPP1, c.244G>T in CLN6, c.554-5A>G in MFSD8 were identified. Potential outcome of the mutations in structure and function of proteins are studied. In addition, we observed some common and unique clinical features of Chinese LINCL patient as compared with those of Western patients, which greatly improved our understanding of the LINCLs.

[Change of CCR7 and CD45RA after blocking of Kv1.3 potassium channel of CD4+ T lymphocytes in multiple sclerosis].

OBJECTIVE: To investigate the changes of CCR7 and CD45RA expression after blocking of the potassium channel Kv1.3 in myelin specific CD4 T lymphocytes and the relation thereof with multiple sclerosis(MS). METHODS: Peripheral blood mononuclear cells were isolated from 15 activated MS patients, 15 INF-beta-1b treated MS patients, and 15 normal controls, CD4+ T lymphocytes were isolated using positive selection method with anti-CD4-coated magnetic beads. To establish culturing MBP special CD4+ T lymphocyte lines, the different groups of T cell were labeled with CD3, CD4, CCR7, and CD45RA fluorescence-antibody or homotype controls and analyzed by four-color flow cytometer. RESULTS: The most part of phenotype in the activated MS patients was CD4+ CCR7- CD45RA- T cells and the percentage was increased after myelin antigen stimulation (P < 0.05), whereas the percentage of CCR7+ CD45RA+ T cells was decreased (P < 0.05). SHK greatly inhibited CCR7- CD45RA- in activated MS (P < 0.05). CCR7-CD45RA- and CCR7+ CD45RA- were in correlation with expanded disability status scale (EDSS) score (r = 0.73, r = 0.705, P < 0.05) in the peripheral blood of activated MS. CONCLUSION: There is a strong correlation between T(EM) phenotype and severity of MS, which may suggest Tem phenotype as the marker to estimate the state of illness. Kv1.3 potassium channel may be the new target in treatment of MS.