AUTOIMMUNITY

Using the new Imaging Mass Cytometry method, researchers of UZH have investigated the pancreas of healthy organ donors and those with type 1 diabetes. The study shows that many beta cells, which normally produce insulin, ...

Relapsing polychondritis is a severe systemic immune-mediated disease characterized by an episodic and progressive inflammatory condition with progressive destruction of cartilaginous structures. This disease has for nearly a century kept secrets not ...

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the presence of pathogenic autoantibodies associated with polyclonal B cell hyperreactivity. Previous study reported that autophagy-related gene Leucine-rich repeat kinase 2 (LRRK2) was likely a susceptible gene for SLE. However, the pathogenic function of LRRK2 in SLE is undefined. Using quantitative PCR, we compared the expression levels of LRRK2 in B cells between SLE patients and healthy controls. The expression levels of LRRK2 in in vitro induced CD19hi B cells and naïve B cells were compared as well based on RNA-seq assay. A pristane-induced lupus-like mouse model was used to explore the effects of LRRK2 on the development of SLE. IgG level, B cell subsets in the spleens and bone marrows and pathological features in the kidneys were compared between wildtype (WT) and Lrrk2−/− littermates. It was obvious that LRRK2 expression was dramatically up-regulated in primary B cells from SLE patients compared to those from healthy controls, as well as in activated CD19hi B cells. More significantly, LRRK2 expression in B cells was positively correlated with system lupus erythematosus disease activity index (SLEDAI), an indicator for disease severity, and serum IgG levels in SLE patients. Negative correlations were observed between LRRK2 expression and serum C3 or C4 levels, two clinical features associated with SLE-related nephritis. LRRK2 deficiency reduced the death rate of pristane treated mice. Decreased levels of total IgG and autoantibody were detected in the serum with less deposition of immune complexes and attenuated pathological symptoms in the kidneys of Lrrk2−/− mice. Consistent with the reduction in IgG production, the percentages of germinal center B cells and plasma cells decreased significantly as well with LRRK2 deficiency. Our study demonstrates that LRRK2 expression is upregulated in B cells from SLE patients with strong correlations to disease severity. LRRK2 deficiency largely attenuates the pathogenic progress of lupus-like features in pristane-induced mice. This is probably achieved through affecting B cell terminal differentiation and subsequent immunoglobulin production.

Journal of Immunology Research is a peer-reviewed, Open Access journal that provides a platform for scientists and clinicians working in different areas of immunology and therapy. The journal publishes research articles, review articles, as well as clinical studies related to classical immunology,...

French experts call for new assessment tools and better use of available treatments...

Diabetes Care. 2019 Jan 18. pii: dc181727. doi: 10.2337/dc18-1727.[Epub ahead of print]...

Amyloid. 2019 Jan 7:1-5. doi: 10.1080/13506129.2018.1549825.[Epub ahead of print]...

Antiphospholipid syndrome, also known as ‘Hughes Syndrome’, is an autoimmune disease characterised by a set of clinical manifestations, almost all of which are direct or indirect sequelae of a hypercoagulable state involving the venous, and to a lesser extent the arterial vasculature.

Newsletter Adipogen...

The new blood test, sclero-smart™, measures levels of anti-vinculin, recently found to be elevated in patients with scleroderma and associated with gastrointestinal complications. This suggests a link between scleroderma and the gut microbiome, a finding that could open the door to discoveries of new microbiome-related therapeutic and diagnostic tools for scleroderma. Gemelli Biotech™, a specialty biotechnology company that develops diagnostics and therapeutics for the human microbiome, announced the commercial availability of sclero-smart™, an ELISA blood test that measures the level of an autoantibody called anti-vinculin in patients who have Systemic Sclerosis and Scleroderma (SSc). The clinical management of patients with SSc is typically very challenging, as the disease progression and organ involvement vary remarkably from individual to individual. There are a number of recognized autoantibody biomarkers that aid in understanding the progression of SSc in an individual. Anti-centromere, Anti-Scl-70 and Anti-RNA-pol-III are amongst the most common. The prevalence of these antibodies in the scleroderma population range from 10-30%. According to an abstract published recently by the American College of Rheumatology, up to 38% of people with scleroderma tested positive for elevated anti-vinculin antibodies, making anti-vinculin more prevalent in the scleroderma population than any other marker currently used for testing. Moreover, scleroderma subjects with elevated anti-vinculin levels had greater gastrointestinal (GI) symptom severity, an association no other marker provides. SSc commonly affects the GI tract, with symptoms including intestinal dysmotility, vomiting, bloating, anorexia, severe abdominal pain, small intestinal bacterial overgrowth (SIBO) and severe malnutrition. No other marker currently available is reliable in predicting the involvement of the GI system. Given the known link between anti-vinculin and intestinal neuropathy, anti-vinculin has substantial potential to serve as a marker for GI complications in scleroderma patients. According to another abstract published by the American College of Rheumatology, anti-vinculin was also associated with pulmonary hypertension. Few markers have an association with this serious vascular complication. Therefore, the measurement of anti-vinculin can be an important test to help rheumatologists identify the risk of GI or vascular complications in scleroderma patients. sclero-smart™ is the only commercially available test that measures anti-vinculin and has been developed through a partnership with the Medically Associated Science and Technology program at Cedars-Sinai. Dr. Mark Pimentel, Executive Director of the MAST program, said We know from a substantial volume of research that bacterial infection in the gut can cause an autoimmune response that involves the abnormal production of anti-vinculin. The connection between anti-vinculin and scleroderma means that the gut microbiome could help us answer many of the questions we still have about diagnosing and treating scleroderma. Matt Mitcho, CEO of Gemelli, added, Given how common the antibody appears to be in the patient population, this test could provide us with a more detailed understanding of the disease’s underlying causes. As a potential catalyst for such a breakthrough, this test is an important development for helping patients with scleroderma.

Journal of Immunology Research is a peer-reviewed, Open Access journal that provides a platform for scientists and clinicians working in different areas of immunology and therapy. The journal publishes research articles, review articles, as well as clinical studies related to classical immunology,...

Estimating the epidemiology of anti-neutrophil cytoplasm antibody-associated renal vasculitis and the role of histologic chronicity in predicting renal outcomes...

Autoimmune antibodies may predict clinical benefit and immune-related adverse events in NSCLC patients receiving programmed cell death protein 1...

Ann Lab Med. 2019 May;39(3):291-298. doi: 10.3343/alm.2019.39.3.291.