Xiaonan Zhong

HLA-DPB1 0501 is associated with susceptibility to anti-aquaporin-4 antibodies positive neuromyelitis optica in southern Han Chinese.

OBJECTIVES To analyze the role of HLA-DRB1 and -DPB1 alleles in the pathogenesis of neuromyelitis optica (NMO) and multiple sclerosis in Southern Han Chinese. METHODS Thirty serum anti-aquaporin 4 antibodies (AQP4-Ab)-positive NMO patients, 53 conventional multiple sclerosis (C-MS) patients, and 93 controls (CTLs) were enrolled. The HLA-DRB1 and -DPB1 alleles of the subjects were determined by sequencing-based typing (SBT). RESULTS The frequency of the DRB1 0901 was lower in NMO patients than in CTLs (P(uncorr)=0.022, OR: 0.194, 95% CI: 0.043-0.876), and DRB1 1602 was higher in NMO patients than in C-MS (P(uncorr)=0.038, OR: 3.491, 95% CI: 1.024-11.896) and CTLs (P(uncorr)=0.051, OR: 2.711, 95% CI: 0.971-7.556). The frequency of DPB1 0501 was significant higher in NMO patients than in C-MS (P(uncorr)=0.018, OR: 4.629, 95% CI: 1.235-17.350) and CTLs (P(uncorr)=0.001, P(corr)=0.022, OR: 7.096, 95% CI: 2.011-25.044). CONCLUSIONS DPB1 0501 correlates with risk of AQP4-Ab positive NMO in Southern Han Chinese.

IL-22 secreting CD4 + T cells in the patients with neuromyelitis optica and multiple sclerosis

Interleukin (IL)-22 secreting CD4(+) T (Th22) cells and IL-22 are involved in the pathogenesis of autoimmune disease, but their role in neuromyelitis optica (NMO) and multiple sclerosis (MS) is unclear. We measured the proportion of Th22, Th17, CD4(+)IL-22(+)IL-17A(+) T cells and serum IL-22 in NMO and MS patients. The proportion of Th22 cells, Th17 cells and serum IL-22 were increased in patients with NMO and MS. Our findings suggest that increased Th22 cells may play an important role in the pathogenesis of NMO and MS.

Interleukin 17 gene polymorphism is associated with anti-aquaporin 4 antibody-positive neuromyelitis optica in the Southern Han Chinese — A case control study

BACKGROUND Interleukin 17 (IL-17) plays an important role in many autoimmune diseases including neuromyelitis optica (NMO) and multiple sclerosis (MS), which are inflammatory demyelinating diseases of the central nervous system. A large number of non-HLA single nucleotide polymorphisms have been reported to increase the risk of MS. However, their effects on NMO have been less well studied. METHODS Fifty-two anti-aquaporin 4 antibody-positive NMO patients, 69 anti-aquaporin 4 antibody-negative conventional MS patients, and 131 controls were genotyped for the IL-17A rs2275913 and IL-17F rs763780 single nucleotide polymorphisms by DNA sequencing. RESULTS Significantly higher frequencies of the rs763780 T allele (p(uncorr)=0.011) and TT genotype (p(uncorr)=0.007, p(corr)=0.042) were observed in NMO patients versus controls. CONCLUSIONS The rs763780 T allele and TT genotype may increase susceptibility to NMO in the Southern Han Chinese.

Cerebrospinal Fluid BAFF and APRIL Levels in Neuromyelitis Optica and Multiple Sclerosis Patients During Relapse

BackgroundBAFF (B-cell activating factor of the tumor necrosis factor family) and APRIL (a proliferation-inducing ligand) are two of the major survival factors for B cells. Many studies have shown that BAFF levels were elevated in MS patients. However, whether the levels of CSF BAFF/APRIL increased in NMO patients was still unclear.ObjectiveTo measure the CSF BAFF and APRIL concentration of in NMO patients, and explore their relationship with disease activity in NMO.MethodsCSF BAFF and APRIL was measured by an enzyme-linked immunosorbent assay (ELISA) in NMO (n = 22), MS (n = 18) patients and controls (n = 14).ResultsConcentration of BAFF and APRIL in NMO patients were significantly higher than MS and controls. CSF BAFF and APRIL levels in controls were also lower than MS. Both NMO and MS revealed an increased disease disability with increased CSF BAFF. CSF APRIL was associated with EDSS scores in NMO, but not found in MS.ConclusionsBAFF/APRIL system considered important for aggressive B cells and T-cell responses, and may stimulates B cells and T cell activation in acute relapse of NMO and MS. In NMO patients, CSF BAFF and APRIL may be key factors of B cell immune response and reflect disease severity.

Notable Increased Cerebrospinal Fluid Levels of Soluble Interleukin-6 Receptors in Neuromyelitis Optica

Background: IL-6 is a proinflammatory cytokine which is involved in the maintenance of the humoral response in various autoimmune disorders. Cerebrospinal fluid (CSF) IL-6 has shown to be increased in neuromyelitis optica (NMO). The soluble form of IL-6 receptor (sIL-6R), which links to IL-6, can activate biological responses in cells. Whether or not sIL-6R is altered in NMO has not been clarified. Objective: To measure CSF IL-6 and sIL-6R in NMO and multiple sclerosis (MS) patients, and investigate whether IL-6 and sIL-6R have possible uses as sensitive biomarkers for diseases activity. Methods: CSF concentrations of IL-6 and sIL-6R were measured by an ELISA in NMO (n = 22) and MS (n = 18) patients, as well as control subjects (n = 14). Results: The concentration of IL-6 levels were higher in NMO compared to MS (p = 0.032) and the controls (p = 0.023). The levels of sIL-6R were also higher in NMO compared to MS (p = 0.002) and the controls (p < 0.001). CSF sIL-6R was associated with an Expanded Disability Status Scale score in NMO (p = 0.005) but not in MS (p = 0.891). In the MS subgroup, sIL-6R concentrations were associated with CSF white blood cells (p = 0.034). Conclusions: Our study revealed that CSF sIL-6R was increased in NMO patients, and correlated with clinical presentations.

Azathioprine plus corticosteroid treatment in Chinese patients with neuromyelitis optica

We investigated the efficacy of azathioprine (AZA) plus long-term low dose corticosteroids in Chinese patients with neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) at the Center for Demyelinating Diseases, South China. We prospectively enrolled patients between June 2010 and June 2014. Annualized relapse rate (ARR), expanded disability status scale (EDSS) score and modified Rankin Scale (mRS) were analyzed retrospectively. Of 77 patients with NMO/NMOSD (four males, 73 females; age range: 4-69 years), median disease duration before initiation of AZA was 32.0 months (range: 2.0-197.0). Median post-treatment follow-up was 23 months (range: 6-58) and 44 patients (57.1%) were relapse-free at median follow-up 19 months (range: 6-51). Pre-treatment ARR was 0.923, and post-treatment ARR was 0 (p < 0.0001). Survival analysis indicated a significantly lower risk of relapse (hazard ratio 0.522; 95% confidence interval 0.377-0.722; p < 0.0001). Significant improvements were shown in the EDSS (3.0 versus 1.0; p < 0.0001) and mRS (2.0 versus 1.0; p < 0.0001). Our study provides evidence supporting the use of AZA plus a low dose corticosteroid as an effective and safe strategy which is associated with a reduction in the risk of relapse in Chinese patients with NMO.

Cerebrospinal fluid levels of CXCL13 are elevated in neuromyelitis optica

BACKGROUND B cells are believed to play an important role in the pathogenesis of NMO. Chemokine (C-X-C motif) ligand 13 (CXCL13), the most potent B-cell chemoattractant, is a chemokine which is critical for secondary lymphoid tissue development and for B-cell migration. Concentration of CXCL13 in cerebral spinal fluid (CSF) is elevated in patients with multiple sclerosis (MS). However, whether levels of CSF CXCL13 are elevated in NMO patients still remain unknown. OBJECTIVE To measure the CSF concentration of CXCL13 in NMO patients, and to determine its relationship with NMO disease activity. METHODS CSF CXCL13 was measured by an enzyme-linked immunosorbent assay (ELISA) in NMO (n=22), MS (n=18) patients and controls (CTLs) (n=12). RESULTS CSF CXCL13 levels in NMO were notable higher than MS (p=0.015) and CTLs (p<0.001), and were related to the NMO disease activity indicated by relapse rate and Expanded Disability Status Scale (EDSS) scores. NMO Patients with the higher relapse rates exhibited the higher CXCL13 concentrations in their CSF; and a trend of increased disease disability with increased CSF CXCL13 level was revealed. The CSF CXCL13 concentrations seemed to associate with CSF white blood cell counting, total protein concentration in NMO subgroup, thought did not quite reach statistical significance (WBC, p=0.473; TP, p=0.276). CONCLUSIONS The concentration of CSF CXCL13 was elevated in NMO patients, and correlated with NMO activity.

Increased plasma levels of pentraxin 3 in patients with multiple sclerosis and neuromyelitis optica

Background: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are immune-mediated inflammatory diseases of the central nervous system. In the acute phase of these diseases, secondary ischemia due to inflammation-induced endothelial dysfunction may be an important pathological change. Pentraxin 3 (PTX3) is a pro-inflammatory protein and a novel biomarker of inflammatory vascular diseases. Objective: We aimed to determine whether PTX3 levels are elevated in MS and NMO patients. Methods: The concentrations of plasma PTX3 were measured using an enzyme-linked immunosorbent assay in 22 MS patients, 26 NMO patients, 15 acute cerebral infarction (CI) patients, 11 mild headache patients, and 14 volunteer controls. Results: During relapse, plasma PTX3 levels were higher in MS patients than in headache patients (p=0.003) and controls (p<0.001). Plasma PTX3 levels were also increased in NMO patients compared with CI patients (p=0.011), headache patients (p<0.001) and controls (p<0.001). CI patients showed elevated PTX3 levels compared with controls (p=0.008). MS and NMO patients showed a trend toward an increased disease disability with higher plasma PTX3 during relapse (MS: p=0.005; NMO: p<0.001). Plasma PTX3 levels were remarkably lower in remission than in the relapse stage (MS: p<0.001; NMO: p<0.001). Conclusion: Plasma PTX3 level is associated with inflammatory responses in MS and NMO.

Cerebrospinal fluid IL-21 levels in Neuromyelitis Optica and multiple sclerosis.

BACKGROUND Neuromyelitis optica (NMO) and multiple sclerosis (MS) are inflammatory demyelinating diseases of human central nervous system (CNS) with complex pathogenesis. IL-21/IL-21R regulates activation, proliferation and survival of both T cells and B cells, which are involved in the pathogenesis of NMO and MS. High levels of serum IL-21 were observed in NMO patients. However, concentration of cerebrospinal fluid (CSF) IL-21 in MS and NMO patients still remain unknown. OBJECT To detect the CSF concentration of IL-21 in NMO and MS patients and to evaluate its relationship with disease activity, particularly concerned about its impact on humoral immunity. METHODS CSF IL-21 was detected by an enzyme-linked immunosorbent assay (ELISA) in NMO patients (n=21), MS patients (n=20) and controls (n=16). RESULTS CSF concentration of the IL-21 was noticeably elevated in NMO (p=0.012) and borderline significantly increased in MS (p=0.115). In addition, this occurrence was associated with humoral immune activity as shown by a correlation between IL-21 and complement in NMO cohort (p=0.023) and high IL-21 levels in autoantibody-positive subgroup (p=0.027). CONCLUSIONS The concentration of CSF IL-21 was noticeably elevated and might have a positive correlation with humoral immune activity in NMO.

Cerebrospinal Fluid High-Mobility Group Box Protein 1 in Neuromyelitis Optica and Multiple Sclerosis

Background: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are two autoimmune inflammatory demyelinating diseases in the central nervous system. Interleukin (IL)-6 and IL-17 may play important roles in the pathogenesis of these diseases. High-mobility group box protein 1 (HMGB1) can activate the nuclear factor light chain enhancer of activated B cells and release cytokines such as IL-6 and IL-17. However, whether cerebrospinal fluid (CSF) HMGB1 levels were altered in NMO and MS patients is still unclear. Objectives: It was our aim to measure the CSF HMGB1 concentration in NMO patients and explore their relationship with IL-6, IL-17 and disease activity. Methods: CSF HMGB1 was measured by enzyme-linked immunosorbent assay in NMO (n = 22) and MS (n = 18) patients as well as in controls (n = 14). Results: CSF HMGB1 was notably higher in the NMO group compared with controls (p = 0.007). CSF HMGB1 positively correlated with IL-6 and IL-17 in NMO patients (IL-6, p = 0.034; IL-17, p < 0.001). Conclusions: In conclusion, our study suggests that CSF levels of HMGB1 are increased in patients with NMO and reflect the neuroinflammatory process.