Blood is key to novel lupus therapy: Study

According to a recent study, the untreatable autoimmune illness lupus, commonly known as systemic lupus erythematosus, may benefit by reestablishing the equilibrium of a blood protein. The immune system is regulated by the protein CXCL5 through neutrophils, a kind of white blood cell. The immune system that typically guards against infections paradoxically assaults healthy tissues and organs in lupus patients, causing inflammation. CXCL5 levels in the blood of lupus patients were found to be much lower than those of healthy people, according to research from Singapore General Hospital (SGH), indicating that the protein may be the cause of lupus activity. Similar outcomes in lupus mouse models were discovered.

The scientists also discovered that weekly CXCL5 injections into animals with severe lupus corrected the CXCL5 balance and increased survival from 25% to over 70% at 10 weeks. Compared to mice treated with saline, there was better renal function and decreased lupus activity. CXCL5 appeared to mitigate the harmful effects of cyclophosphamide, allowing the mice to survive for up to two years when combined with cyclophosphamide, an established powerful immunosuppressive therapy for lupus.

The research’s results were released last month in Arthritis & Rheumatology, one of the best peer-reviewed rheumatology publications, and Nature Reviews Rheumatology will feature it as a significant study in November 2022. SingHealth, a public healthcare cluster of which SGH is a member, submitted a patent for these findings, and it has now been approved in the USA and Singapore.

“We are excited about the possibility of a new treatment option for lupus as 30 to 60 per cent of patients do not respond to conventional medications despite aggressive regimens. In the past 65 years, only three drugs for lupus have been approved by the United States Food and Drug Administration but these drugs have modest efficacy. There is therefore a real and urgent need for better therapies, particularly for the more severe spectrum of lupus that we see in Asia,” said senior author Associate Professor Andrea Low, Head and Senior Consultant, Department of Rheumatology & Immunology, SGH.

“Our study has shown CXCL5 to be safe. There was no liver or kidney toxicity or cancer inducing effects. Major components of the immune system were also not compromised. We hope to take our findings further to improve the care of patients with lupus,” said principal investigator Dr Fan Xiubo, Senior Research Fellow, Department of Clinical Translational Research, SGH.

SingHealth, a public healthcare cluster of which SGH is a member, submitted a patent for these findings, and it has now been approved in the USA and Singapore.

As it affects vital organs including the kidneys, heart, lungs, and brain, lupus has the potential to be fatal. According to reports, there are 100 cases of lupus for every 100,000 persons globally. Asians are more likely to have a severe case of the illness, which generally affects more women than males between the ages of 15 and 45.

“It is gratifying to see that this research that started over 8 years ago, has led to a discovery that has the potential to offer patients with lupus new treatment options in future,” said Professor William Hwang, Senior Consultant, Department of Haematology, SGH, who co-led the early phases of the study. Prof Hwang is also CEO of the National Cancer Centre Singapore.

“To be in the forefront of medicine means we have to constantly further our understanding of diseases and offer patients better treatment options through rigorous scientific research. I’m heartened that the team has shed new light on lupus and the possibility of a more efficacious therapy for patients some years down the road,” said Professor Fong Kok Yong, Deputy Group CEO (Medical and Clinical Services), SingHealth, and Senior Consultant, Department Rheumatology & Immunology, SGH.