Aimin Wu

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

OBJECTIVESnTo analyze the role of HLA-DRB1 and -DPB1 alleles in the pathogenesis of neuromyelitis optica (NMO) and multiple sclerosis in Southern Han Chinese.nnnMETHODSnThirty 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).nnnRESULTSnThe 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).nnnCONCLUSIONSnDPB1 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.

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 (nu2009=u200922), MS (nu2009=u200918) patients and controls (nu2009=u200914).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.

Aquaporin 4 Antibodies in the Cerebrospinal Fluid Are Helpful in Diagnosing Chinese Patients with Neuromyelitis Optica

Objective: It was the aim of this study to compare the diagnostic efficiency of anti-aquaporin 4 (AQP4) antibody detection between serum and cerebrospinal fluid (CSF) samples in Chinese patients with central nervous system demyelinating diseases. Methods: Anti-AQP4 antibodies were detected by a cell-based assay. We calculated the sensitivity, specificity and coherence in 118 patients with neuromyelitis optica (NMO, n = 39), multiple sclerosis (n = 34), longitudinally extensive transverse myelitis (LETM, n = 22), optic neuritis (ON, n = 6), opticospinal multiple sclerosis (n = 8) and acute partial transverse myelitis (n = 9). Results: Forty-four serum samples (33.8%) were positive for anti-AQP4 antibodies. Anti-AQP4 antibody seropositivity was 76.9, 59.1 and 16.7% in patients with NMO, LETM and ON, respectively. Sixty-five CSF samples (50%) were positive for anti-AQP4 antibodies. Anti-AQP4 antibody positivity was 87.1, 81.8, 83.3, 62.5 and 11.8% in patients with NMO, LETM, ON, opticospinal multiple sclerosis and multiple sclerosis, respectively. The ĸ value of the coherence test was 0.585 (p < 0.0001) between the two types of samples. The antibody positivity rate was significantly different between the two body fluids (p = 0.0008, McNemar test). The sensitivity and specificity were 74.3 and 100% in serum, 85.7 and 88.2% in CSF, and 94.3 and 88.2% for serum and CSF combined, respectively. Conclusion: The sensitivity of anti-AQP4 antibodies in the CSF was higher than that in the serum, and their combined use is helpful in diagnosing Chinese patients with NMO.

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.

Cerebrospinal fluid levels of CXCL13 are elevated in neuromyelitis optica

BACKGROUNDnB 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.nnnOBJECTIVEnTo measure the CSF concentration of CXCL13 in NMO patients, and to determine its relationship with NMO disease activity.nnnMETHODSnCSF CXCL13 was measured by an enzyme-linked immunosorbent assay (ELISA) in NMO (n=22), MS (n=18) patients and controls (CTLs) (n=12).nnnRESULTSnCSF 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).nnnCONCLUSIONSnThe concentration of CSF CXCL13 was elevated in NMO patients, and correlated with NMO activity.

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

BACKGROUNDnNeuromyelitis 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.nnnOBJECTnTo 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.nnnMETHODSnCSF IL-21 was detected by an enzyme-linked immunosorbent assay (ELISA) in NMO patients (n=21), MS patients (n=20) and controls (n=16).nnnRESULTSnCSF 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).nnnCONCLUSIONSnThe concentration of CSF IL-21 was noticeably elevated and might have a positive correlation with humoral immune activity in NMO.

Acute transverse myelitis in demyelinating diseases among the Chinese

The aim of the study was to characterize the demographic, clinical, and prognostic features of Chinese patients with acute transverse myelitis (ATM). The clinical data from ATM patients in a demyelinating disease database were analyzed retrospectively. Sixty-seven ATM patients with a follow-up duration longer than 2xa0years were identified. The frequency of neuromyelitis optica-related ATM (NMO-ATM) was high in our cohort (40.3%). Recurrent ATM (R-ATM), with a female predominance, was common in total idiopathic ATM (69.0%, 20/29). In R-ATM with longitudinally extensive spinal cord lesions (LESCLs), the high seropositivity of NMO-IgG, spinal cord lesions mostly involved the central gray matter and severer long-term disability were similar to NMO-ATM. In RTM without LESCLs, low seropositivity of NMO-IgG, preferentially involvement of the peripheral white matter and relative better neurological recovery were consistent with multiple sclerosis-related ATM (MS-ATM). The transition rates to MS in patients with acute partial transverse myelitis (APTM) and acute complete transverse myelitis (ACTM) were not significant (16.7 vs. 6.3%, Pxa0=xa00.753), while LESCLs (ORxa0=xa011.4, Pxa0=xa00.028) were significantly correlated with transition to NMO. The presence of LESCLs was the only variable showing a higher risk for reaching Rankin 3 (hazard ratio: 2.5, 95% CI: 1.0–6.1). Chinese patients with ATM had demographic, clinical, and prognostic features different from those in Western populations. Idiopathic R-ATM, common in Chinese, is a heterogeneous entity that shares partial clinical, spinal MRI and prognostic features with MS-ATM and NMO-ATM. The length of spinal cord lesion, rather than APTM/ACTM, may be a prognostic factor associated with clinical outcome and long-term disability in our population.

Serum uric acid levels and neuromyelitis optica

Uric acid (UA) has been reported to be reduced in the serum of patients with multiple sclerosis (MS) and optic neuritis (ON). However, the relationship between UA and neuromyelitis optica (NMO) was unknown. NMO was claimed to be a distinct nosologic entity from MS. The aim of our study was to investigate the correlation between serum UA level and the clinical characteristics of NMO. The serum UA level was measured in 403 Chinese patients; 69 with NMO, 32 ON, 127 MS, 80 cerebral infarction (CI) patients, and 95 healthy controls (CTL). Serum UA level in NMO was significantly lower than that in CI (249.89xa0±xa093.74 vs. 315.42xa0±xa085.57xa0μmol/L, pxa0=xa00.004) and CTL (249.89xa0±xa093.74 vs. 314.33xa0±xa0102.05xa0μmol/L, pxa0<xa00.0001). However, no difference was found between NMO and MS (pxa0=xa00.496) or NMO and ON (pxa0=xa00.858). When the analysis was performed in the female cohort separately, UA level was significantly lower in females than in males in all groups. It was also shown in our study that UA level in patients with NMO was not correlated with disease activity revealed by MRI, disease disability or duration of disease. Our results indicated a reduced serum UA level in patients with NMO.

Hemoglobin A1C is independently associated with severity and prognosis of brainstem infarctions

OBJECTIVEnTo assess the association of Hemoglobin A1C (HbA1c) with acute brainstem infarctions (BSIs) and to determine whether HbA1c is an independent risk factor in BSIs patients.nnnMETHODSn96 only BSIs patients were categorized into four groups according to HbA1c as <6%, ≥ 6% but <7%, ≥ 7% but <8%, or ≥ 8%, respectively. The association of the four HbA1c groups with diffusion-weighted imaging (DWI) infarct volumes (DIV), National Institutes of Health Stroke Scale (NIHSS), and follow-up modified Rankin Scale (FmRS) scores were analyzed. Patients also were categorized into two groups according to HbA1c<6% or ≥ 6%. Logistic regression analyses were performed to determine independent risk factors.nnnRESULTSnThere was a significant correlation between HbA1c and DIV (Spearman ρ=0.339, P=0.001), NIHSS scores (ρ=0.292, P=0.004) and FmRS scores (ρ=0.315, P=0.002). The incidence of pons infarction was highest in BSIs and patients with HbA1c ≥ 6% showed significantly more frequent isolated pontine infarction. Logistic regression analyses showed that only HbA1c was independently associated with larger DIV (P=0.025) and FmRS scores (P=0.026).nnnCONCLUSIONSnThese results suggest that elevated HbA1c level may be a potential serologic marker in the evaluation of the severity and prognosis of acute BSIs. There is an urgent need to study control of diabetes mellitus (DM) before and after BSIs.