[Mechanism of Th1/Th2 Cytokines in HLA-DQ8 Transgenic Mice Model of Ocular Experimental Autoimmune Myasthenia Gravis].

Objective To analyze the levels of cytokines (IL-2,IFN-γ,IL-6,IL-10) associated with Th1 and Th2 cells in HLA-DQ8 transgenic mice model of ocular experimental autoimmune myasthenia gravis (oEAMG) induced by recombinant H-AChR γ subunit immunization.Methods DQ8 mice were immunized with 20 µg of AChR γ subunit,20 µg of crude E. coli extract (E. coli group),or complete Freund's adjuvant (CFA) only (CFA group). All mice were immunized on days 0,30,and 60. Mice were euthanized 28 days after the third immunization,and draining lymph node cells (LNC) and spleen lymphocytes were cultured in vitro. The supernatant was collected to observe the interleukin(IL)-2,interferon(IFN)-γ,IL-6,IL-10 production by ELISA.Results LNCs and spleen lymphocytes of H-AChR γ subunit-immunized mice exhibited significantly enhanced IFN-γ (F=76.332,P<0.001;F=34.865,P<0.001) and IL-2 (F=42.835,P<0.001;F=38.030,P<0.001),which associated with Th1 cells,as compared to E. coli group and CFA group. There were no significant differences in IL-6 (F=1.325,P=0.284;F=1.935,P=0.166) and IL-10 (F=0.908,P=0.417;F=1.189,P=0.322) levels,which secreted by Th2 cells,among these three groups.Conclusion Th1 cytokines play key roles in the pathogenesis of oEAMG,while the mechanism of Th2 cytokines for oEAMG remains unclear.

Comparisons of the therapeutic effects of three different routes of bone marrow mesenchymal stem cell transplantation in cerebral ischemic rats.

Bone marrow mesenchymal stem cells (BMSCs) are mainly administered via three routes: intra-arterial, intravenous and intracerebral. It has been reported that BMSC administration via each route ameliorates the functional deficits after cerebral ischemia. However, there have been no comparisons of the therapeutic benefits of BMSC administration through different delivery routes. In this study, we injected BMSCs into a rat model of transient middle cerebral artery occlusion (MCAO) through the intra-arterial, intravenous, or intracerebral route at day 7 after MCAO. Control animals received only the vehicle. Neurological function was assessed at post-ischemic days (PIDs) 1, 7, 14, 21, 28 and 35 using behavioral tests (modified Neurological Severity Score (mNSS) and the adhesive removal test). At PID 35, the rat brain tissues were processed for histochemical and immunohistochemical staining. Our results showed that BMSC transplantation via the intra-arterial, intravenous, and intracerebral routes induced greater improvement in neurological functions than the control treatments; furthermore, the intra-arterial route showed the greatest degree and speed of neurological functional recovery. Moreover, BMSCs treatment through each route enhanced reconstruction of axonal myelination in the area of the corpus callosum on the infarct side of the cerebral hemisphere, increased the expression of SYN and Ki-67, and decreased the expression of Nogo-A in the brain. These effects were more apparent in the intra-arterial group than in the intravenous and intracerebral groups. These data suggest that BMSCs transplantation, especially through intra-arterial delivery, can effectively improve neurological function intra-arterial. The underlying mechanism may include the promotion of synaptogenesis, endogenous cell proliferation, and axonal regeneration.

Association of susceptibility to multiple sclerosis in Southern Han Chinese with HLA-DRB1, -DPB1 alleles and DRB1-DPB1 haplotypes: distinct from other populations.

Association of HLA class II with multiple sclerosis (MS) has been widely studied in both Western and Oriental populations. However, such an association is not well documented in Chinese. The objective of this study was to examine the association between the susceptibility to conventional MS in Southern Chinese with HLA-DRB1,-DPB1 alleles and putative DRB1-DPB1 haplotypes. Genotyping of HLA-DRB1 and -DPB1 alleles was performed in 60 patients with conventional MS and 95 controls. Allele frequencies were compared between patients and controls to identify MS-associated alleles. Relative predisposing effect method was used to compare haplotype frequencies in patients and controls and to identify possible predisposing DRB1-DPB1 haplotypes, which were further examined for differences in haplotype carriage rates between the two groups. We found that the allele frequency of DRB1*1501 was not different between patients (18.3%) and controls (21.1%) (p = 0.837). In contrast, frequency of the DPB1*0501 allele was significantly higher in patients (90%) than in controls (67.4%) (odds ratio = 4.36, p = 0.0013, pcorr = 0.025). DRB1-DPB1 linkage haplotype in patients (8.33%) was significantly higher than in controls (0%) (p < 0.0001) and the carriage rate of this haplotype was significantly increased in patients (15%) as compared with controls (0%) (p = 0.00013, pcorr = 0.003). Combined, these results suggest that HLA-DRB1*1501 is not associated with susceptibility to conventional MS in Southern Chinese. Instead, both the DPB1*0501 allele and the DRB1*1602- DPB1*0501 haplotype are strong predisposing factors for conventional MS in this population. Our results establish that the HLA profiles of MS in Southern Chinese are distinct from other populations.

Balo's disease showing benign clinical course and co-existence with multiple sclerosis-like lesions in Chinese.

Baló's concentric sclerosis (BCS) is a rare demyelinating disorder usually considered a variant of multiple sclerosis (MS). However, its pathogenesis and its correlation with MS remains unclear and controversial. This report presents seven Hans Chinese subjects diagnosed as BCS on the basis of the pathognomonic MR (magnetic resonance) findings. Upon diagnosis, all the cases displayed good responses to corticosteroids and showed an overall benign prognosis during a follow-up period of 4-13.5 years, although three relapsed later. MR findings suggest that the characteristic concentric lesions of BCS frequently (5/7) coexist with multiple sclerosis-like lesions. During follow-up, the Baló-like lesions may either dissolve over time or transform into an MS-like lesion. Moreover, the Balóand MS-like lesions occurred one after another at the onset and relapse phases of the same patient in two cases. These clinical features suggest that Baló's disease showing benign clinical course and co-existence of multiple sclerosis (MS)-like lesion is not rare among the Chinese, and strengthens the notion that BCS correlates intrinsically with MS.

[Association of HLA-DRB1 and -DPB1 allele polymorphism with multiple sclerosis in Chinese Han population from Southern areas].

OBJECTIVE: To examine the correlation between multiple sclerosis (MS) in Chinese Southern Han population and the polymorphism of HLA-DRB1 and -DPB1 alleles, and compare it to the reports of Western, Japanese and Northern Chinese populations. METHODS: The HLA-DRB1 and -DPB1 alleles of 26 patients with conventional MS (C-MS), 13 patients with optic-spinal form of MS (OS-MS), and 50 normal controls were determined by sequence-based typing (SBT) method. The frequency of the HLA alleles was compared between the 2 MS subtypes and the MS subtypes and the controls by chi(2) or Fisher exact probability test. The P values were corrected according to Bonferroni's method to calculate corrected the P values (Pc). RESULTS: A total of 27 HLA-DRB1 alleles and 13 HLA-DPB1 alleles were identified in the 39 MS patients and 50 controls. The frequencies of DRB1(*)0406 (P = 0.014, OR = 2.09) and DRB1(*)1302 alleles (P = 0.007, OR = 2.84) were higher in the OS-MS patients than in the controls. In addition, the DRB1(*)120201 allele was more frequent in the C-MS patients than in the controls, and the frequency of DPB1(*)2101 was higher in the OS-MS patients than in the controls. However, all the differences were of no significance since the corrected P values (Pc) were all > 0.1. There was no correlation between the MS subtypes and the HLA-DRB1(*)1501 or DPB1(*)0501 as reported in Western and Japanese populations (all P > 0.1). CONCLUSION: The correlation between HLA-DRB1 and -DPB1 in Southern Han MS population is different from that in the Western, Japanese, and Northern Chinese populations. Southern Han MS patients may be linked to the HLA-DRB1(*)0406, DRB1(*)1302, DRB1(*)120201 and DPB1(*)2101, but not to the HLA-DRB1(*)1501 or DPB1(*)0501 alleles as reported in the above populations.