Removal of B1b B cells protective against lupus

2015 Mackay group. L-R: Beatriz Garcillan, Aurelie Baldolli, Fabien Vincent, Ellen McAllister, Fabienne Mackay, Angela Nguyen, Pin Shie Quah, Rachel Lim, Florence Lim, Will Figgett

By Dr Jodie Abramovitch

Systemic lupus erythematosus (SLE), commonly known as lupus, is an autoimmune disease with no cure. Monash researchers have been working to understand the immunological causes of lupus in a mouse model so as to better understand the disease in humans. Such groundwork will enable the development of much more effective therapies for the treatment of lupus.

Professor Fabienne Mackay (former head of the Department of Immunology and Pathology), together with the department's Leukocyte Signalling laboratory headed by Associate Professor Margaret Hibbs  have discovered that a certain type of innate B cell (immune cell), known as a B1b B cell, may be critical in the development of lupus.

Two types of mature B cells that are activated by toll-like receptor (TLR) signalling are B1 B cells and marginal zone (MZ) B cells. In the mouse model studied, these cells cause disease by infiltrating various tissues such as the salivary glands and kidneys. When the MZ and B1a B cells were removed from the mice, disease still occurred. When B1b B cells were removed also, mice were protected from all symptoms of lupus. Therefore B cells and CD19 signalling, specifically innate B cells, are very important in the development of lupus and may represent a target for treatment.

Reference: Fairfax KA, Tsantikos E, Figgett WA, Vincent FB, Quah P, LePage M, Hibbs ML, Mackay F. BAFF driven autoimmunity requires CD19 expression. J Autoimmun. 2015 Aug; 62: 1-10
doi:10.1016/j.jaut.2015.06.001

Breakthrough opens door to safer lupus drugs

Prof Fabienne Mackay's group. Lead research Dr Will Figgett
seated far left, Fabienne Mackay next to him. Pin Shie Quah,
another author on the paper, standing immediately behind
Fabienne.

A ground-breaking discovery by Monash University researchers could revolutionise treatments given to lupus sufferers, saving thousands of people each year from serious illness or death caused by secondary infections.

Lupus is a debilitating and widespread autoimmune disease that can attack any part of the body. It affects one in 1,000 Australians and 5 million people worldwide, and its victims are typically young women. Indigenous and Asian people suffer higher rates than other groups.

The BAFF/APRIL system in SLE pathogenesis: Nature Reviews Rheumatology



Animation of body's
'safety procedure'

Department of Immunology researchers have published a review of their recent research on the BAFF/APRIL system, a complex of the cytokines BAFF and APRIL, their receptors and signalling pathways. The efficacy of belimumab, an anti-BAFF biologic agent used in clinical trials for SLE, is used to develop an argument that the BAFF/APRIL system is an important regulator of autoimmunity. Future therapies for SLE could fine-tune these cytokine signalling pathways to regulate autoreactive B cell survival and autoimmunity.  This review encompasses three recent research articles from teams headed by Professors Fabienne Mackay & Eric Morand.
Link: Nature Review Rheumatology article

Publication: Clinical associations of serum interleukin-17 in systemic lupus erythematosus

Vincent FB, Northcott M, Hoi A, Mackay F, Morand EF. Clinical associations of serum interleukin-17 in systemic lupus erythematosus. Arthritis Research & Therapy 2013,15:R97 doi:10.1186/ar4277. Abstract

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.