SciCombinator

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Concept: Autoimmune diseases

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B cells contribute to multiple aspects of autoimmune disorders and may play a role in triggering disease. Thus, targeting B cells may be a promising strategy for treating autoimmune disorders. Better understanding of the B cell subsets that are responsible for the development of autoimmunity will be critical for developing efficient therapies. Here we have reported that B cells expressing the transcription factor T-bet promote the rapid appearance of autoantibodies and germinal centers in spontaneous murine models of systemic lupus erythematosus (SLE). Conditional deletion of T-bet from B cells impaired the formation of germinal centers and mitigated the development of kidney damage and rapid mortality in SLE mice. B cell-specific deletion of T-bet was also associated with lower activation of both B cells and T cells. Taken together, our results suggest that targeting T-bet-expressing B cells may be a potential target for therapy for autoimmune diseases.

Concepts: Cell nucleus, Rheumatoid arthritis, Systemic lupus erythematosus, Lupus erythematosus, Glomerulonephritis, Autoimmune diseases, Sjögren's syndrome, Myasthenia gravis

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Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis.

Concepts: Vasculitis, Wegener's granulomatosis, Autoimmune diseases, Arthritis, Granuloma, Anti-neutrophil cytoplasmic antibody, Proteinase 3, Vascular-related cutaneous conditions

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Celiac disease (CD) is an autoimmune disorder that occurs in genetically susceptible individuals of all ages and is triggered by immune response to gluten and related proteins. The disease is characterized by the presence of HLA-DQ2 and/or DQ8 haplotypes, diverse clinical manifestations, gluten-sensitive enteropathy and production of several autoantibodies of which endomysial, tissue transglutaminase and deamidated gliadin peptide antibodies are considered specific. Although anti-reticulin antibodies (ARA) have historically been used in the evaluation of CD, these assays lack optimal sensitivities and specificities for routine diagnostic use. This review highlights the advances in CD-specific serologic testing and the rationale for eliminating ARA from CD evaluation consistent with recommendations for diagnosis.

Concepts: Immune system, Antibody, Immunology, Autoimmune diseases, Autoimmunity, Coeliac disease, Gliadin, Triticeae glutens

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Chronic leg ulcers in patients with rheumatological diseases can cause significant morbidity. We performed a retrospective case review to describe the epidemiology, clinical features and outcome of chronic leg ulcers in this group of patients. Twenty-nine patients with underlying rheumatological conditions, namely, rheumatoid arthritis (15 patients), systemic lupus erythematosus (8 patients), overlap syndromes (3 patients), systemic sclerosis (1 patient) and ankylosing spondylitis (1 patient) were included. The ulcers were mostly located around the ankle (55·2%) and calves (37·9%). The predominant aetiology of the ulcers, in decreasing order of frequency, was venous disease, multifactorial, vasculitis or vasculopathy, infective, pyoderma gangrenosum, ischaemic microangiopathy and iatrogenic. Treatment modalities included aggressive wound bed preparation, compression therapy (17 patients), changes in immunosuppressive therapy (15 patients), hyperbaric oxygen therapy (4 patients) and cellular skin grafting (2 patients). Management of chronic leg ulcers in rheumatological patients is challenging and the importance of careful clinicopathological correlation and treatment of the underlying cause cannot be overemphasised.

Concepts: Osteoporosis, Rheumatoid arthritis, Rheumatology, Systemic lupus erythematosus, Lupus erythematosus, Autoimmune diseases, Arthritis, Immunosuppressive drug

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ABSTRACT:: Pyodermatitis-pyostomatitis vegetans (PPV) constitutes an inflammatory mucocutaneous dermatosis that is associated with inflammatory bowel disease. Clinically, PPV appears as pustules on mucosal surfaces and as vegetating exudative plaques on intertriginous surfaces. It is typically a clinical diagnosis supported by histological findings. Microscopic findings include epidermal hyperplasia, focal acantholysis, and a dense mixed inflammatory infiltrate with intraepithelial and subepithelial eosinophilic microabscesses. In the recent literature, immunofluorescence has been thought to be negative in PPV or, if positive, an aberrant finding. Herein, we report 2 cases of PPV associated with inflammatory bowel disease, which display intercellular IgA deposits. Although these cases may represent isolated epiphenomena, it is possible that the paucity of PPV cases with immunofluorescent studies hitherto has led to an oversight of an interesting association between intercellular IgA and PPV.

Concepts: Immune system, Inflammation, Anatomical pathology, Ulcerative colitis, Inflammatory bowel disease, Autoimmune diseases, Pemphigus, Pemphigus vegetans

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Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) is an autosomal recessive disease due to mutations of the autoimmune regulator (AIRE) gene. Typical manifestations include candidiasis, Addison’s disease, and hypoparathyroidism. Type 1 diabetes, alopecia, vitiligo, ectodermal dystrophy, celiac disease and other intestinal dysfunctions, chronic atrophic gastritis, chronic active hepatitis, autoimmune thyroid disorders, pernicious anemia and premature ovarian failure are other rare associated diseases although other conditions have been associated with APECED.

Concepts: Immune system, Endocrinology, Autoimmune diseases, Autoimmunity, Malabsorption, Addison's disease, Pernicious anemia, Atrophic gastritis

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Fas is a transmembrane receptor involved in the death program of several cell lines, including T lymphocytes. Deleterious mutations hitting genes involved in the Fas pathway cause the autoimmune lymphoprolipherative syndrome (ALPS). Moreover, defective Fas function is involved in the development of common autoimmune diseases, including autoimmune syndromes hitting the nervous system, such as multiple sclerosis (MS) and chronic inflammatory demyelinating polyneuropathy (CIDP). In this review, we first explore some peculiar aspects of Fas mediated apoptosis in the central versus peripheral nervous system (CNS, PNS); thereafter, we analyze what is currently known on the role of T cell apoptosis in both MS and CIDP, which, in this regard, may be seen as two faces of the same coin. In fact, we show that, in both diseases, defective Fas mediated apoptosis plays a crucial role favoring disease development and its chronic evolution.

Concepts: Immune system, Central nervous system, Nervous system, Multiple sclerosis, Myelin, Autoimmune diseases, Chronic inflammatory demyelinating polyneuropathy, Peripheral nervous system

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Systemic Lupus Erythematosus is an autoimmune disease characterized by the formation of anti-nuclear autoantibodies, particularly anti-chromatin. Although the aetiology of the disease has not yet been fully elucidated, several mechanisms have been proposed to be involved. Due to an aberrant apoptosis or decreased removal of apoptotic cells, apoptotic blebs containing chromatin are released. During apoptosis, chromatin is modified that increases its immunogenicity. Myeloid dendritic cells (myDC) can take up apoptotic blebs and stimulate autoreactive T helper cells, and subsequently the formation of autoantibodies by autoreactive B cells. Immune complexes formed by anti-chromatin autoantibodies and modified chromatin deposit on basal membranes, and incite a local inflammation, but can also stimulate plasmacytoid dendritic cells to produce IFN-α. In addition to apoptotic blebs, neutrophil extracellular traps released by dying neutrophils, in a process called NETosis, may serve as a source of autoantigens as well. In this review, we describe the role of both apoptosis and NETosis in the pathogenesis of SLE, and show how both processes may interact with each other.

Concepts: Immune system, Cell nucleus, Rheumatoid arthritis, Systemic lupus erythematosus, Lupus erythematosus, Glomerulonephritis, Autoimmune diseases, Sjögren's syndrome

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Primary sclerosing cholangitis (PSC) is strongly associated with inflammatory bowel disease (IBD). The aim of this study was to assess the IBD phenotype associated with PSC in a large well-phenotyped population-based PSC cohort using endoscopic and histopathologic criteria.

Concepts: Inflammation, Ulcerative colitis, Colonoscopy, Gastroenterology, Inflammatory bowel disease, Autoimmune diseases, Primary sclerosing cholangitis

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Raynaud’s phenomenon often precedes the diagnosis of systemic sclerosis and is the first symptom of the disease in many cases. Antinuclear antibody positivity can assist in the early identification of cases of isolated Raynaud’s phenomenon likely to progress to systemic sclerosis. However, the specific differences between rate of progression for different scleroderma hallmark antibodies is less clear. We review the predictive potential of ANA positivity and nailfold capillaroscopy for identifying cases of Raynaud’s phenomenon which may progress to connective tissue diseases. We also have reviewed data from our own large scleroderma cohort to explore the relationship between antibody subtype and time to development of SSc. Duration of pre-existing Raynaud’s phenomenon may be an important determinant of the profile of systemic sclerosis cases identified through screening. Ninety-five percent of our patients with isolated Raynaud’s phenomenon, negative autoimmune serology on more than one visit and normal capillaroscopy score showed no progression to connective tissue disease. Duration of antecedent Raynaud’s phenomenon differs between disease subsets and scleroderma-specific ANA patterns.

Concepts: Immune system, Blood, Rheumatology, Autoimmune diseases, Scleroderma, Systemic scleroderma, Raynaud's phenomenon, CREST syndrome