Frequency of autoimmune disorders and autoantibodies in patients with neuromyelitis optica.

OBJECTIVE: The aim of this study was to report the frequency of autoimmune disorders and autoantibodies in 22 patients with neuromyelitis optica (NMO), as well as whether the seropositivity for autoantibodies differs between anti-aquaporin 4 (AQP4) positive and AQP4 negative NMO patients. METHODS: Demographic, medical records, and a profile of autoantibodies were evaluated in 22 NMO patients, including AQP4, anti-thyroid-stimulating hormone receptor, antinuclear antibodies (ANA), anti-thyroperoxidase (anti-TPO), anti-thyroglobulin (anti-Tg), anti-double-stranded DNA, anti-neutrophil cytoplasmic, anti-cyclic citrullinate peptide, rheumatoid factor, anti-SSA/Ro, anti-SSB/La, anti-Smith antibodies (anti-Sm), anti-ribonucleoprotein, anti-nucleosome, and anti-Scl70. Thyroid-stimulating hormone and free thyroxin were measured. RESULTS: The frequency of women was higher than men (95.5% vs. 4.5%) and 68.2% were Afro-Brazilians. Six (27.3%) patients presented other autoimmune disorders, such as Hashimoto thyroiditis (n=2), Graves' disease (n=1), juvenile idiopathic arthritis (n=1), systemic lupus erythematosus and systemic sclerosis (n=1), and Raynaud's phenomenon (n=1). The most frequent autoantibodies were anti-AQP4 (54.5%), anti-nucleosome (31.8%), ANA (27.3%), anti-TPO (22.7%), and anti-Tg (22.7%). Difference was not observed in the frequency of autoimmune disorders when the patients were compared according to their anti-AQP4 status. CONCLUSION: The results of the present study underscored that the NMO patients present high frequency of autoantibodies against cellular antigens and the presence of autoimmune disorders. Further studies with large number of NMO patients may contribute to advances in the understanding of NMO disease mechanisms.

Postpartum Treatment With Immunoglobulin Does Not Prevent Relapses of Multiple Sclerosis in the Mother.

Multiple sclerosis (MS) is a chronic, neurological, immune-mediated disease that can worsen in the postpartum period. There is no consensus on the use of immunoglobulin for prevention of disease relapses after delivery. We have shown that the controversial beneficial effect of immunoglobulin given immediately after birth could not be observed in patients with MS.

Genetic, Immune-Inflammatory, and Oxidative Stress Biomarkers as Predictors for Disability and Disease Progression in Multiple Sclerosis.

The aim of this study was to evaluate the TNFß NcoI polymorphism (rs909253) and immune-inflammatory, oxidative, and nitrosative stress (IO&NS) biomarkers as predictors of disease progression in multiple sclerosis (MS). We included 212 MS patients (150 female, 62 male, mean (±standard deviation (SD)) age = 42.7 ± 13.8 years) and 249 healthy controls (177 female, 72 male, 36.8 ± 11 years). The disability was measured the Expanded Disability Status Scale (EDSS) in 2006 and 2011. We determined the TNFß NcoI polymorphism and serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-4, IL-10, and IL-17, albumin, ferritin, and plasma levels of lipid hydroperoxides (CL-LOOH), carbonyl protein, advanced oxidation protein products (AOPPs), nitric oxide metabolites (NOx), and total radical-trapping antioxidant parameter (TRAP). The mean EDSS (±SD) in 2006 was 1.62 ± 2.01 and in 2011 3.16 ± 2.29, and disease duration was 7.34 ± 7.0 years. IL-10, TNF-α, IFN-γ, AOPP, and NOx levels were significantly higher and IL-4 lower in MS patients with a higher 2011 EDSS scores (≥3) as compared with those with EDSS < 3. The actual increases in EDSS from 2006 to 2011 were positively associated with TNF-α and IFN-γ. Increased IFN-γ values were associated with higher pyramidal symptoms and increased IL-6 with sensitive symptoms. Increased carbonyl protein and IL-10 but lowered albumin levels predicted cerebellar symptoms. The TNFB1/B2 genotype decreased risk towards progression of pyramidal symptoms. Treatments with IFN-ß and glatiramer acetate significantly reduced TNF-α but did not affect the other IO&NS biomarkers or disease progression. Taken together, IO&NS biomarkers and NcoI TNFß genotypes predict high disability in MS and are associated with different aspects of disease progression. New drugs to treat MS should also target oxidative stress pathways.

Epidemiological, clinical, and immunological characteristics of neuromyelitis optica: A review.

The aim of this study was to review the epidemiological and clinical characteristics of neuromyelitis optica (NMO) and the immunopathological mechanisms involved in the neuronal damage. NMO is an inflammatory demyelinating autoimmune disease of the central nervous system that most commonly affects the optic nerves and spinal cord. NMO is thought to be more prevalent among non-Caucasians and where multiple sclerosis (MS) prevalence is low. NMO follows a relapsing course in more than 80-90% of cases, which is more commonly in women. It is a complex disease with an interaction between host genetic and environmental factors and the main immunological feature is the presence of anti-aquaporin 4 (AQP4) antibodies in a subset of patients. NMO is frequently associated with multiple other autoantibodies and there is a strong association between NMO with other systemic autoimmune diseases. AQP4-IgG can cause antibody-dependent cellular cytotoxicity (ADCC) when effector cells are present and complement-dependent cytotoxicity (CDC) when complement is present. Acute therapies, including corticosteroids and plasma exchange, are designed to minimize injury and accelerate recovery. Several aspects of NMO pathogenesis remain unclear. More advances in the understanding of NMO disease mechanisms are needed in order to identify more specific biomarkers to NMO diagnosis.

Tumor necrosis factor beta NcoI polymorphism is associated with inflammatory and metabolic markers in multiple sclerosis patients.

To evaluate the association between the tumor necrosis factor beta (TNF-ß) NcoI polymorphism and inflammatory and metabolic markers in patients with multiple sclerosis (MS) patients and the association of these markers with disease disability, a 782 base-pair fragment of the TNF-ß gene was amplified from genomic DNA and digested with the NcoI restriction enzyme. The serum levels of numerous cytokines (IL-1ß, IL-12, IL-6, TNF-α, IFN-γ, IL-4, IL-10, and IL-17) serum lipid levels, plasma insulin levels, and the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) levels were evaluated in 123 female and 43 male patients with MS. Females carrying the TNFB2/B2 genotype presented with decreased IL-4 and IL-10 levels and increased TNF-α, glucose, insulin, and HOMA-IR levels; moreover, there were positive correlations between EDSS and glucose and between EDSS and HOMA-IR in these females. Males carrying the TNFB2/B2 genotype exhibited increased levels of TNF-α, IFN-γ, and IL-17 (p=0.0326) and decreased levels of IL-4, IL-10, insulin, and HOMA-IR; there was a positive correlation between EDSS and TNF-α levels. The TNFB2/B2 genotype of TNF-ß NcoI polymorphism was associated with increased inflammatory and metabolic markers and this association was different according to sex of MS patients.