The molecular pathology of autoimmune diseases

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The position of a gene on a chromosome. When the same gene has different versions in different people, these versions called "alleles" still occupy the same locus. A technique used to quantify proteins such as antibodies and antigens based on how they scatter light when put in a solution. A technique used to determine the presence of antibodies in the patient's serum, revealed by their binding to a purified antigen of interest attached to a plastic plate.

After binding to the antigen, the patient antibodies are detected by the addition of a commercially-available antibody directed against human antibodies that has been coupled to an enzyme. A technique used to determine the presence of antibodies in the patient's serum, revealed by their binding to a purified antigen of interest attached to magnetic beads. After binding to the antigen, the patient antibodies are detected by the addition of a commercial antibody directed against human antibodies that has been coupled to a light-emitting molecule.

A technique used to determine the presence of antibodies in the patient's serum, revealed by their binding to a particular tissue substrate of interest. After binding to the tissue, the patient antibodies are detected by the addition of a commercial antibody directed against human antibodies that has been coupled to a fluorescent dye. Immune checkpoints are molecules that normally regulate the immune response by putting a brake on T cells.

When checkpoints are inhibited, T cells become unleashed and can be used to destroy cancer cells. At the same time, this inhibition of the checkpoints makes T cells more capable of causing autoimmune diseases. T cells that recognize antigens belonging to the patient such as thyroglobulin in he thyroid or myosin in the heart , rather than antigens in bacteria and viruses. Several forms of alteration of the immune system where the normal balance between the various immune components is altered. A disease initiated by infection with some Streptococcus species where the patient makes antibodies against these bacteria that however also recognize with heart antigens, such as cardiac myosin.

Also known as B cells, these lymphocytes have a surface receptor specific for one of many antigens. Improved understanding of cell migration in the synovial joint, including the associated cellular and environmental factors, might reveal new therapeutic strategies for joint diseases such as rheumatoid arthritis and osteoarthritis and have important implications for tissue engineering of the joint.

Review Article 12 December Nakazawa and colleagues describe advances in our understanding of anti-neutrophil cytoplasmic antibody-associated vasculitis. These insights have already generated promising new treatments that target B cells, T cells and cytokines; potential novel approaches targeting additional cells or molecules are also discussed. Review Article 11 December The treatment of systemic lupus erythematosus involves a balance between control of disease activity and prevention of therapeutic harm that requires careful optimization.

In this Review, the authors discuss available and emerging therapeutic strategies that exploit the current drug armamentarium. Review Article 12 November Stromal cells of mesenchymal origin can help to sustain inflammation in the joint by various mechanisms; understanding these mechanisms could inform new therapeutic strategies and explain why joint inflammation persists in diseases of the joint such as arthritis, enthesopathy and tendinopathy. Review Article 06 November Hydroxychloroquine is a front-line treatment for systemic lupus erythematosus and other rheumatic diseases, but can cause retinopathy.

Improved detection techniques for the early stages pre-symptomatic of retinopathy has led to recommendations for reduced dosing, but more data on the efficacy of low-dose hydroxychloroquine are needed. Review Article 19 October The ability to resolve, rather than suppress, inflammation could enable new possibilities for the treatment of chronic diseases such as rheumatoid arthritis.

Knowing more about the function of immune-regulatory cytokines is the first step towards realizing their therapeutic potential. Review Article 09 October Both spondyloarthritis and uveitis are associated with HLA-B27 positivity. This Review discusses this overlap and how the intestinal microbiome and dysbiosis might contribute to the development of both diseases. Review Article 15 August Preclinical rheumatoid arthritis RA is characterized by the presence of RA-related autoantibodies in the serum in the absence of clinical symptoms.

This Review discusses the relationships during this period between mucosal alterations and the initiation of local and systemic anti-citrullinated protein antibody production. Review Article 12 July Leukocytes travel through many different tissues during their lifetime, being educated by the cells and environments they encounter. An increased understanding of this journey in the context of rheumatoid arthritis offers hope for the development of future therapies.

Review Article 21 June A growing body of evidence indicates that neutrophils and neutrophil extracellular traps NETs are involved in the progression of rheumatic diseases. This Review focuses on the role of NETs in systemic lupus erythematosus, vasculitis, rheumatoid arthritis and gout. Review Article 31 May Endothelial dysfunction is thought to be an important contributor to the increased risk of cardiovascular diseases seen in patients with rheumatoid arthritis.

Microvascular endothelial dysfunction could be a useful predictive marker of cardiovascular events in early rheumatoid arthritis. Review Article 21 March Platelets mediate many non-haemostatic responses, including immune responses, through the production or release of various mediators. Platelets are activated in systemic lupus erythematosus and are implicated in its pathogenesis, and present opportunities for therapeutic intervention.

Review Article 08 February Review Article 24 January The heterogeneity of autoimmune rheumatic diseases, and their shared clinical and molecular features, makes classifying and diagnosing these diseases difficult and highlights the need for a new taxonomy. Reclassifying these diseases according to the underlying molecular mechanisms might lead to novel insights into disease mechanisms and enable better patient stratification. Review Article 11 January Preclinical studies suggest that the lymphatic system has a critical role in the pathogenesis and therapy of inflammatory-erosive arthritis.

These findings, and complementary data from human studies, highlight the translational potential of assessing and modulating the lymphatic system in patients with chronic arthritis. Review Article 19 December Primary immunodeficiency syndromes and autoimmune diseases seem to be different, but the clinical symptoms can be very similar. In this Review, the authors examine the causes and pathogenesis of several primary immunodeficiency syndromes and highlight their relationship to rheumatic diseases. Science and Society 07 December Large partnerships between academia and industry are emerging as a possible solution to the problems surrounding stratified medicine.

In this Perspectives article, the members of the RA-MAP Consortium reflect on the challenges and benefits of working in such a partnership. Review Article 21 November Primary and secondary failure of TNF antagonists can affect treatment strategies for rheumatoid arthritis. This article discusses the implications of immunogenicity, as well as methodological problems related to the detection of antidrug antibodies and trough drug levels.

Review Article 09 November The symptomatic pre-arthritis phase of rheumatoid arthritis RA is hypothesized to be part of a 'window of opportunity' for preventive treatment. This Review discusses the methodological considerations when designing and interpreting preventive trials, and translating findings into clinical practice. Review Article 14 September Serum autoantibodies have a wide range of glycosylation patterns. In this Review, the authors describe the role of autoantibody glycosylation in the pathology of autoimmune disease, and how understanding the role of specific antibody glycoforms might optimize current treatment approaches.

Review Article 24 August The amount of clinical, serological and experimental evidence linking periodontitis to rheumatoid arthritis is constantly increasing. In this Review, Potempa and colleagues lay out the case for periodontal pathogens in the pathogenesis of rheumatoid arthritis. Review Article 13 July Advances in synovial tissue research have improved our understanding of inflammatory arthritides, particularly rheumatoid arthritis, and have identified potential biomarkers that could be used for diagnosis, disease stratification, and predicting disease course and treatment response.

Autoimmune diseases | Nature Reviews Rheumatology

Opinion 01 June The need to accurately assess the effectiveness of biologic therapies for rheumatoid arthritis in real-world settings has seen an explosion in nationwide biologics registers. In this Perspectives article, the authors discuss how to make the most of data from such registers. Opinion 25 May The presence of antinuclear antibodies ANAs is an important criterion for the classification of autoimmune diseases such as systemic lupus erythematosus, but the specificity of ANA tests is controversial.

This Perspectives article critically discusses the methods used in ANA testing for different diseases, as well as ways to improve the use of these assays in clinical and research settings. Kitahama, Y. Kawakami, et al. J Clin Endocrinol Metab, 83 , pp. Figueroa-Vega, M. Cuesta-Mateos, F. Moreno-Otero, R. Tie-2 is overexpressed by monocytes in autoimmune thyroid disorders and participates in their recruitment to the thyroid gland. J Clin Endocrinol Metab, 94 , pp. Pyzik, E. Grywalska, B. Matyjaszek-Matuszek, J. Immune disorders in Hashimoto's thyroiditis: what do we know so far?.

J Immunol Res, , pp. Thyroid, 17 , pp. Curr Opin Endocrinol Diabetes Obes, 21 , pp. Kristensen, L. Lundy, M. Brimnes, T. Smith, C. Eshaghkhani, M. Sanati, M. Nakhjavani, R. Safari, A. Khajavi, M. Ataei, et al. Minerva Endocrinol, 41 , pp. Weetman, M. Yateman, P. Ealey, C. Black, C. Reimer, R.

Williams Jr. Thyroid-stimulating antibody activity between different immunoglobulin G subclasses. J Clin Invest, 86 , pp. Evans, J. Sanders, T. Tagami, P. Sanders, S. Young, E. Roberts, et al. Monoclonal autoantibodies to the TSH receptor, one with stimulating activity and one with blocking activity, obtained from the same blood sample.

Clin Endocrinol Oxf , 73 , pp. Latrofa, G. Chazenbalk, P. Pichurin, C. Chen, S. McLachlan, B. J Clin Endocrinol Metab, 89 , pp. Sakaguchi, K. Wing, Y. Onishi, P. Prieto-Martin, T. Regulatory T cells: how do they suppress immune responses?. Int Immunol, 21 , pp. Wang, G. Chen, Y. Fan, M. Van Antwerp, J. Endocrinology, , pp. Gambineri, T. Torgerson, H. Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance IPEX , a syndrome of systemic autoimmunity caused by mutations of Foxp3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol, 15 , pp.

Marazuela, M. Figueroa-Vega, H. Regulatory T cells in human autoimmune thyroid disease. J Clin Endocrinol Metab, 91 , pp. Nakahara, Y. Nagayama, T. Ichikawa, L. Yu, G.

Eisenbarth, N. The effect of regulatory T-cell depletion on the spectrum of organ-specific autoimmune diseases in non-obese diabetic mice at different ages. Autoimmunity, 44 , pp. Pan, Y. Shin, G. Gopalakrishnan, J. Hennessey, L. De Groot. Clin Endocrinol, 71 , pp.

The Molecular Pathology of Autoimmune Diseases

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Autoimmune Hepatitis (Lupoid hepatitis)

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Autoimmune disease

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Sedgwick, et al. IL drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med, , pp. Yang, K. Hirahara, J. T helper 17 cell heterogeneity and pathogenicity in autoimmune disease. Trends Immunol, 32 , pp. Lee, A. Awasthi, N. Yosef, F.

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