Systemic lupus erythematosus (SLE) is a disease affecting the kidneys and seems to be very difficult to treat. A recent research commenced by the National Institutes of Health is alleged to have unraveled that the activation of immune cells called basophils causes kidney damage. Displayed in a mouse model of lupus nephritis, the findings may pave the path for new treatments of SLE disease.
Previous analysis has concluded mice that lack the protein Lyn kinase show exaggerated responses to allergens early in life and face a lupus-nephritis-like disease in later life. During the analyses scientists had scrutinized the increase of immunoglobulin E (IgE) responses to normally harmless substances. But this research employed a mouse model to show the way basophils are activated by self-reactive IgE antibodies. These anti-bodies are known to attack themselves instead of germs and seemingly add to the kidney damage linked with SLE.
“We are excited by the potential of these findings in the treatment of lupus. Obviously, whether omalizumab treatment or other strategies to reduce basophil activation in lupus will prove efficacious remains to be seen. Nonetheless, this work opens new avenues of investigation in lupus and, at the very least; we have gained an understanding of how autoantibody production is enhanced in this disease,” alleged Juan Rivera, Ph.D., senior author of the research and deputy scientific director at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the NIH institute.
The findings also reveal that in case absence of self-reactive IgEs or depleting the population of basophils is encouraged many characteristics of the kidney disease are supposedly diminished. The investigators explained that self-reactive IgEs possibly attached to the surface of basophils tend to reside in the mouse’s spleen and lymph nodes. Here they cause a cascade of cellular events to occur which in turn boost the production of more self-reactive antibodies. These antibodies are believed to harm the kidneys by probably binding with other proteins to form immune complexes that are deposited in the organ. The patient may then suffer from inflammation, damage and progressive loss of kidney function.
In order to confirm if results displayed by the mouse were similar to humans the investigators tested blood samples from 44 people with SLE. They supposedly discovered self-reactive IgEs and an elevation in activated basophils. Identical results did not appear in the blood samples of healthy controls. Both the factors revealed a powerful link with disease activity and lupus nephritis in the people with SLE. They recommended potential therapeutic benefits for decreasing the levels of self-reactive IgE or of activated basophils. The drug omalizumab usually suggested for asthma is believed to block IgE from binding to the surface. Also potential activation of basophil cells apparently avoids basophils from promoting kidney inflammation.
The scientists further aim to organize a safety research of omalizumab in people with SLE. They will also undertake an experiment to explore other ways to prevent IgEs from binding with basophils. They further aim to ascertain whether or not depleting or inactivating the basophil population might reduce the production of self-reactive antibodies that can lead to kidney damage in SLE.
The research is published online in Nature Medicine.