'Multi-target' immune therapy improves outcomes of severe lupus nephritis
From China comes some promising lupus news. A new treatment using a combination of drugs targeting different parts of the immune system improves the recovery rate for patients with severe lupus involving the kidneys, according to a new Chinese study reported in the Journal of the American Society of Nephrology.
The study included 40 patients with severe lupus nephritis, characterized by widespread inflammation and decreasing kidney function. Typically such disease is treated with a single immunosuppressive drug, but efficacy is usually poor. Because the impact of severe lupus on the kidney involves various parts of the immune system, researchers at the Research Institute of Nephrology of Jinling Hospital in Nanjing, China, decided to treat the different immune targets with a combination of immunosuppressant drugs.
Participants were divided into two groups – one group of patients received this "multi-target" therapy, consisting of the immunosuppressant drugs tacrolimus (Prograf) and mycophenolate mofetil (CellCept) – commonly used as anti-rejection drugs in transplant patients – plus a steroid. The other group received standard treatment with a single immunosuppressant drug, cyclophosphamide (Cytoxan).
The complete remission rate, with recovery of normal kidney function, was about four times higher among lupus patients receiving the three-drug combination. Overall, 95 percent of patients in the multi-target therapy group had partial or complete remission, compared to 55 percent with single-drug therapy. The rate of most adverse effects was also lower with multi-target therapy.
Although the study was small, its results suggest using a combination of drugs that affect different immune targets improves the chances of remission for patients with severe lupus nephritis. Larger, longer-term studies are needed to confirm the findings.
Abnormal 'editing' of gene messages may be cause of lupus
Researchers at Wake Forest University in Winston-Salem, N.C., have uncovered evidence that the abnormal “editing” of gene messages in a type of white blood cell may be behind the development of lupus.
The findings, reported online in the journal Immunology, involve an enzyme that “edits” and modifies the messages of genes before the protein-making process. Protein molecules are what carry out the instructions of our genes and determine how an organism looks, how well its body metabolizes food or fights infection, and even how it behaves.
In lupus, the normal editing process goes awry, causing a shift in the balance of proteins that results in impaired functions in T cells, a type of white blood cell involved in the regulation of immune functions. The current research was based on earlier findings that one of the three enzymes involved in editing gene messages,150-kDa ADAR1, is higher in the T cells of lupus patients compared to those without lupus.
Senior author Dama Laxminarayana, PhD, made the initial finding about 150-kDa ADAR1 levels in 2002 and has been working to solve the mystery of how it is related to the development of lupus. In the current study, he found that the higher levels of 150-kDa ADAR1 alter the editing induced by two other enzymes and may cause an imbalance of proteins, causing normal editing to go awry. The researchers are now working to find a safe way to block the enzyme to treat the disease, so stay tuned for more lupus news.
In addition, Laxminarayana says 150-kDa ADAR1 could be used as a biomarker to detect the disease earlier, to monitor how patients respond to therapy, and to measure disease intensity.
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