Autoimmune Diseases最新文献

Systemic Lupus Erythematosus (SLE) is a clinically heterogeneous autoimmune disease with strong genetic and environmental components. Our objective was to replicate 25 recently identified SLE susceptibility genes in two distinct populations (Chinese (CH) and Malays (MA)) from Malaysia. We genotyped 347 SLE cases and 356 controls (CH and MA) using the ImmunoChip array and performed an admixture corrected case-control association analysis. Associated genes were grouped into five immune-related pathways. While CH were largely homogenous, MA had three ancestry components (average 82.3% Asian, 14.5% European, and 3.2% African). Ancestry proportions were significantly different between cases and controls in MA. We identified 22 genes with at least one associated SNP (P < 0.05). The strongest signal was at HLA-DRA (P Meta = 9.96 × 10(-9); P CH = 6.57 × 10(-8), P MA = 6.73 × 10(-3)); the strongest non-HLA signal occurred at STAT4 (P Meta = 1.67 × 10(-7); P CH = 2.88 × 10(-6), P MA = 2.99 × 10(-3)). Most of these genes were associated with B- and T-cell function and signaling pathways. Our exploratory study using high-density fine-mapping suggests that most of the established SLE genes are also associated in the major ethnicities of Malaysia. However, these novel SNPs showed stronger association in these Asian populations than with the SNPs reported in previous studies.

Developmental exposure to environmental toxicants may induce immune system alterations that contribute to adult stage autoimmune disease. We have shown that continuous exposure of MRL+/+ mice to trichloroethylene (TCE) from gestational day (GD) 0 to postnatal day (PND) 49 alters several aspects of CD4(+) T cell function. This window of exposure corresponds to conception-adolescence/young adulthood in humans. More narrowly defining the window of TCE developmental exposure causes immunotoxicity that would establish the stage at which avoidance and/or intervention would be most effective. The current study divided continuous TCE exposure into two separate windows, namely, gestation only (GD0 to birth (PND0)) and early-life only (PND0-PND49). The mice were examined for specific alterations in CD4(+) T cell function at PND49. One potentially long-lasting effect of developmental exposure, alterations in retrotransposon expression indicative of epigenetic alterations, was found in peripheral CD4(+) T cells from both sets of developmentally exposed mice. Interestingly, certain other effects, such as alterations in thymus cellularity, were only found in mice exposed to TCE during gestation. In contrast, expansion of memory/activation cell subset of peripheral CD4(+) T cells were only found in mice exposed to TCE during early life. Different windows of developmental TCE exposure can have different functional consequences.

At a time when health is being recognized as more than just avoiding death, age and comorbidity are becoming increasingly important aspects of chronic disease. Systemic Lupus Erythematous (SLE) is probably one of the best paradigms of modern chronic disease, sitting at the crossroads of numerous somatic health problems, immune activation, depression, pain, and fatigue. One hundred forty-eight female participants were enrolled in the present study: 50 diagnosed with SLE, 45 with major depressive disorder (MDD), and 53 age-matched controls. Statistically significant lower scores in quality-of-life dimensions related to physical impairment were found in SLE. Patients with MDD presented significant levels of pain, reduced physical summary component (PSC), and general health scores different from healthy controls. Fatigue was reported in 90% of women with SLE and 77.8% of the MDD patients in contrast with 39.6% in the control group. Significant correlations were seen among fatigue severity, age, and educational level in SLE. From our own previous work and more recent work on the association of immune activation and depression, unexplained fatigue in SLE may signify an early sign of immune activation flare-up. The search for cytokine markers should perhaps be extended to fatigue in SLE.

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly throughout the industrialized world. Its most prominent pathologic features are lesions involving the retinal pigment epithelium (RPE) the Bruch's membrane, the degeneration of photoreceptors, and, in the most aggressive cases, choroidal neovascularization. Genetic associations between the risk of developing AMD and polymorphism within components of the complement system, as well as chemokine receptors expressed on microglial cells and macrophages, have linked retinal degeneration and choroidal neovascularization to innate immunity (inflammation). In addition to inflammation, players of the adaptive immunity including cytokines, chemokines, antibodies, and T cells have been detected in animal models of AMD and in patients suffering from this pathology. These observations suggest that adaptive immunity might play a role in different processes associated with AMD such as RPE atrophy, neovascularization, and retinal degeneration. To this date however, the exact roles (if any) of autoantibodies and T cells in AMD remain unknown. In this review we discuss the potential effects of adaptive immune responses in AMD pathogenesis.

Seronegative spondyloarthritis (SpA) are variably associated with HLA-B∗27 antigen. HLA-B∗27 negative SpA has also been reported from different parts of the world. There is paucity of data on this entity from Indian subcontinent. We studied 100 consecutively diagnosed HLA-B27 negative spondyloarthritis patients from a tertiary care center in India. Modified New York Criteria for ankylosing spondylitis (AS) and ESSG criteria for SpA were used for diagnosing patients. HLA-B∗27 typing was done by an in-house PCR-SSP technique in SpA patients to exclude B∗27 positive patients and PCR-SSOP technique was used to type 100 B∗27 negative SpA patients and 100 controls from the same ethnicity. Frequency of B∗07 was significantly increased (B∗07: % PF 54 versus 18; OR 5.348; 95% CI 2.808-10.186; P value 1.14E - 07), whereas frequency of B∗40 was significantly decreased (B∗40: % PF 17 versus 32; OR 0.435; 95% CI 0.222-0.850; P value 0.013) when compared with B∗27 negative controls. Among 100 SpA patients, 47 were undifferentiated spondyloarthritis and 33 patients were reactive arthritis patients. 40% of the patients were suffering from polyarticular arthritis, 35% had pauciarticular arthritis with knee joint, hip joint, ankle joint, and SI joint involvement. We conclude that B∗07 was significantly associated with B27 negative spondyloarthropathy from Western India and majority of B∗27 negative patients were uSpA.

Periodontal diseases are characterized by localized infections and inflammatory conditions that directly affect teeth supporting structures which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidences of involvement of immunopathology have been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses. This review is an attempt to throw light on the etiopathogenesis of periodontal disease highlighting the autoimmunity aspect of the etiopathogenesis involved in the initiation and progression of the disease. However, further clinical trials are required to strengthen the role of autoimmunity as a cause of periodontal disease.

The majority of neurodegenerative (ND) and autoimmune diseases (AID) remain idiopathic. The contribution of environmental chemicals to the development of these disorders has become of great interest in recent years. A convergence of mechanism between of ND and AID development has also emerged. In the case of ND, including neurotoxicity, the focus of this review, work over the last two decade in the realm of biomarker development, indicates that the immune response provides a venue whereby humoral immunity, in the form of autoantibodies to nervous system specific proteins, or neuroantibodies (NAb), may provide, once validated, a sensitive high throughput surrogate biomarker of effect with the potential of predicting outcome in absence of overt neurotoxicity/neurodegeneration. In addition, NAb may prove to be a contributor to the progression of the nervous system pathology, as well as biomarker of stage and therapeutic efficacy. There is a compelling need for biomarkers of effect in light of the introduction of new chemicals, such as nanoengineered material, where potential neurotoxicity remains to be defined. Furthermore, the convergence of mechanisms associated with ND and AID draws attention to the neglected arena of angiogenesis in defining the link between environment, ND, and AID.

Objectives. Studies have suggested a correlation between untreated celiac disease and risk for other autoimmune diseases. We investigated the prevalence of thyroid autoimmunity in 12-year-old children (i) with symptomatic celiac disease diagnosed and treated with a gluten-free diet, (ii) with screening-detected untreated celiac disease, and (iii) without celiac disease. Methods. Blood samples from 12632 children were collected. All celiac disease cases, previously diagnosed and newly screening-detected, were identified. Per case, 4 referents were matched. Blood samples were analyzed for autoantibodies against thyroid peroxidase (TPOAb). The cut-off value for TPO positivity was set to 100 U/mL. Results. Altogether, 335 celiac disease cases were found. In the entire celiac disease group, 7.2% (24/335) had elevated titers of TPOAb compared to 2.8% (48/1695) of the referents. Among the previously diagnosed celiac disease cases, 7.5% (7/93, OR 2.8, 95% CI 1.2-6.4) was TPOAb positive and among screening-detected cases, 7.0% (17/242, OR 2.6, 95% CI 1.5-4.6) was TPOAb positive. Conclusion. Children with celiac disease showed a higher prevalence of thyroid autoimmunity. We could not confirm the hypothesis that untreated celiac disease is associated with increased risk of developing thyroid autoimmunity. Early initiation of celiac disease treatment might not lower the risk for other autoimmune diseases.

Background. It has been hypothesized that various infective agents may activate immune reactions as part of the atherosclerotic process. We aimed to investigate the interrelationship between chronic exposure to oral pathogens and immune-inflammatory response in patients with acute coronary atherothrombosis. Patients and Methods. The study included 200 participants from Serbia: 100 patients with acute myocardial infarction (MI), and 100 age- and sex-matched controls. Antibodies to oral anaerobes and aerobes were determined as well as autoantibodies to endothelial cells, beta-2 glycoprotein I, platelet glycoprotein IIb/IIIa and anticardiolipin. Interleukin-6 (IL-6) and C-reactive protein (CRP) were measured. Results. The mean serum antibodies to oral anaerobes tended to be higher among subjects with MI (0.876 ± 0.303 versus 0.685 ± 0.172 OD, P < 0.001). Similarly, antibody levels against oral aerobes in patients were significantly different from controls. Antibodies against endothelial cell, beta-2 glycoprotein I, platelet glycoprotein IIb/IIIa, anticardiolipin along with CRP and IL-6 were highly elevated in patients. The levels of antibodies to oral bacteria showed linear correlation with tissue antibodies, CRP and IL-6. Conclusion. Antibody response to chronic oral bacterial infections and host immune response against them may be responsible for the elevation of tissue antibodies and biomarkers of inflammation which are involved in acute coronary thrombosis development.