Cross-disciplinary research links golden staph to autoimmune disease

Prof. Peleg with his lab group.

Professor Anton Peleg, Director of Infectious Diseases, recently collaborated on a paper published in Nature Communications.

The study found that the body may be fooled by a plasmid-derived protein from some types of Staph aureus (golden staph), resulting in the development of severe autoimmune disease. Plasmids have been associated with antibiotic resistance but this study now links them to autoimmune disease, specifically ANCA-associated vasculitis (AAV), a severe autoimmune disease caused by autoimmunity to myeloperoxidase (MPO).

Research needed for autoimmune hepatitis patients' salvage therapy

Autoimmune hepatitis is a chronic inflammatory liver disease
not readily treatable for 20% of patients

by Anne Crawford

Autoimmune hepatitis is a chronic inflammatory liver disease. The condition is treatable for the large majority of patients. The 20 per cent or so of patients who don’t respond well to standard medicines are treated with “salvage therapies”, but until now these have been inadequately scrutinised for their efficiency and safety, a new paper says.

Monash University researchers in the Department of Gastroenterology at The Alfred Hospital have conducted a rare, comprehensive review of salvage therapies resulting in findings that could benefit clinicians and their patients with the disease globally.

Translational Research Symposium Speaker Spotlight: Professor Richard Kitching

Prof Richard Kitching

Monash University's 3rd annual Translational Research Symposium is being hosted by its three metropolitan clinical schools on 31 July 2017. The symposium will host a diverse group of medical researchers presenting their work into translational research. RSVP here.

Professor Richard Kitching is a head of the Autoimmune Kidney Disease and Vasculitis research group at Monash School of Clinical Sciences and a leading Nephrologist at Monash Health.

Findings shed light on autoimmune role in thymus

Associate Professor Menno van Zelm

by Anne Crawford

It has been known for almost three decades that B cells exist in the thymus but their function there has been unclear. Associate Professor Menno van Zelm explored this neglected area and has arrived at world-first findings answering this riddle which may lead to a better understanding of the origin of autoimmune diseases.

Preventing the development of multi-organ autoimmunity

By Dr Jodie Abramovitch

Autoimmune disease occurs when the immune system incorrectly recognises self-tissues and organs as being potentially dangerous - like a pathogen. The immune system attacks the tissue or organ – sometimes in an organ-specific manner (eg. type I diabetes) or sometimes in a multi-organ fashion (eg. lupus) – which leads to disease symptoms. What causes the onset of autoimmune disease is not well understood and, consequently, there is no cure with treatments predominantly aimed at relieving inflammatory symptoms.

Elisha de Valle - first author of this study

In a collaborative study, Monash researchers examined the role of transcription factor NF-κB1 in a specific type of immune cell, Follicular B cells (Fo B cells), and its role in controlling multi-organ autoimmune disease. NF-κB1 is important for regulating B cell function and when Fo B cells become deregulated they can produce antibodies that target and destroy vital organs. The authors of this study used a mouse model that lacks the NF-κB1 gene and analysed the effect on Fo B cells. They found that Fo B cells lacking NF-κB1 secreted a large amount of pro-inflammatory factor IL-6 and this had an effect on surrounding immune cells. Specifically, IL-6 led to the over stimulation of B cells which resulted in the formation of  germinal centre structures (sites where antibody responses are launched) and, in turn, an increase in the presence of self-reacting antibodies against self-tissues and organs within the NF-κB1 deficient mice. Moreover, IL-6 also caused Fo B cells to proliferate at a higher rate which exacerbated the germinal centre B cell response. Without NF-κB1, the mice developed severe multi-organ autoimmune disease and had a reduced life span compared to healthy mice. This was largely attributable to the production of IL-6 by Fo B cells. Importantly, when IL-6 was blocked the development of autoimmune disease was greatly reduced.

This study revealed that NF-κB1 has an essential role in controlling the function of Fo B cells, primarily to limit the production of inflammatory factor IL-6. In the absence of NF-κB1, the production of IL-6 becomes deregulated and severe autoimmune disease can occur. These conclusions further the understanding of the mechanisms that control IL-6 production and may lead to better management of patients with autoimmune disease.

Reference: de Valle E, Grigoriadis G, O'Reilly LA, Willis SN, Maxwell MJ, Corcoran LM, Tsantikos E, Cornish JK, Fairfax KA, Vasanthakumar A, Febbraio MA, Hibbs ML, Pellegrini M, Banerjee A, Hodgkin PD, Kallies A, Mackay F, Strasser A, Gerondakis S, Gugasyan R. NFκB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells. J Exp Med. 2016 Apr; 213:621-41. 

doi: 10.1084/jem.20151182.

B cell control in the immune system: review article

B cell control mechanisms

Department of Immunology researchers have published an article reviewing the control of B cells by a group of proteins called TNF superfamily proteins. These proteins trigger necessary signals that activate or regulate the various protective functions of B cells in the immune system, and they are important to understand because B cell pathologies including some cancers or autoimmunity can occur when these functions are disrupted.

Body's 'safety procedure' could explain autoimmune disease

Immunology researchers have found an important safety mechanism in the immune system that may malfunction in people with autoimmune diseases, such as Multiple Sclerosis, potentially paving the way for innovative treatments. Published in Immunity, 6 Sept 2013, the research, led by Head of the Monash Department of Immunology Professor Fabienne Mackay, describes for the first time how the body manages marginal zone (MZ) B cells, which form a general first line of attack against germs, but are potentially harmful.

• Monash story
• Journal reference
• Animation prepared by first author Dr Will Figgett;
• Video of Fabienne Mackay explaining the significance of the research;
• BAFF lab link.

Slowing down SLE kidney disease

Systemic lupus erythematosus (SLE), more simply known as lupus, is an autoimmune disease where the body makes antibodies against its own DNA. It may involve a variety of genes, follow a variety of genetic pathways, and damage a variety of cell types. In many cases, the consequence is impairment of kidney function, which is known as glomerulonephritis.