Lupus treatments

Lupus treatments can be tailored to patient’s individual cells, study shows

Lupus treatments can be tailored to patient's individual cells, study shows

The kidneys of patients living with systemic lupus erythematosus (SLE) are often under assault, and not all those living with the disease will respond to standard treatment. A new report published in the journal Nature Immunology online May 20 shows how tissue samples from these patients can accurately predict those more likely than not to respond to therapy. SLE is a disease marked by the attack on joints, skin, and kidneys by the body’s immune system.

“Our latest research redefines how a kidney biopsy can be used to tailor drug therapy in lupus patients,” says study co-senior investigator Jill Buyon, MD, the Sir Deryck and Lady Va Maughan Professor of Rheumatology at NYU School of Medicine. “Moreover, our results point to simple skin biopsy as a potential tool to track the progression of kidney damage from the disease and to tell whether treatments are working as intended or need to be changed.”

Researchers say treating lupus, which afflicts an estimated 1 million Americans, predominantly women, is difficult because its onset, symptoms, and progression vary significantly from patient to patient over time. The disorder’s origins remain unknown, although many suspect that genetic factors passed down from parents to their children as well as environmental triggers, such as sun exposure and infection, are likely responsible.

Multiple organs, including the brain and linings of the heart and lungs can be involved, the researchers add, making it harder to detect where the disease started or to predict which tissues will be affected. Existing therapies focus on immune-suppressing drugs designed to check any attack. However, these treatments are not cures and only relieve SLE signs and symptoms, such as joint pain, difficulty breathing, and low blood cell counts in some patients.

For the new study, researchers analyzed the cellular profile and genetic activity of kidney and skin tissue samples from 21 SLE patients in the New York area. Most were women between the ages of 16 and 53, and of all races. Study participants were at the time of biopsy also among the half of all SLE patients who experience lupus nephritis, a form of kidney inflammation that can cause lasting damage to the organ.

Researchers used a gene-mapping tool called scRNA-Seq that allowed them to track the action of more than 4,000 specific cells. The cell-specific biopsy profiles from patients having lupus-related kidney “flares” were then compared with biopsy results from three women who did not have lupus or any other known disease.

Specifically, the study showed similar immune system signaling and scar-forming gene activity in kidney tubular cells affected by lupus and skin keratinocyte cells from the same patients.

Gene activity from exposure to an immune cell signaling protein, type 1 interferon (IFN), in both cell types from SLE patients increased 3.8 times and 2.5 times, respectively, when compared with biopsies from healthy women. Moreover, the increase in scar-forming gene activity in the kidney cells of SLE patients was observed in those who did not respond to therapy.

Researchers say finding similarities between cell activation in the kidney and skin is important because the skin can be more easily and repeatedly biopsied than the kidney. And since cellular changes observed in the skin closely mirrored changes involved in SLE kidney damage, sampling skin could, they say, offer clues as to what, if any, malfunction is about to occur in the kidney.

Buyon says IFN typically shows up in cells as part of the immune system response to infection and for decades has been linked to lupus. The latest study reinforces its role, as yet unexplained, in the disease.

While researchers have plans to determine the source of the IFN affecting both types of cells, they say their immediate next step is to analyze results from 160 additional patients’ kidney biopsies and as many as 400,000 different cells. They also plan to test additional skin cells, with assistance from the NYU Colton Center for Autoimmunity, for differences between lupus patients with and without nephritis.

“If confirmed in further experiments, our findings could personalize lupus therapy based on what an individual patient’s cells are telling us about immune activity,” says Buyon, director of rheumatology in the Department of Medicine at NYU Langone Health, where she also serves as director of its Lupus Center. “Moreover, this research should help shed light on the underlying biological pathways behind organ injury in lupus, the interrelated roles of kidney and skin cells, and how type 1 interferon propels this disease.”

Source: EurekaAlert

factors may trigger lupus

Environmental factors may trigger lupus onset and progression

Environmental factors may trigger lupus onset and progression

While genetics play a role in the development of Lupus, a systemic autoimmune disease that can attack any organ system in the human body, so do environmental triggers, such as particulates in air pollution and ultraviolet light, explains Gaurav Gulati, MD, a physician-researcher at the University of Cincinnati (UC) College of Medicine.

“The tough part about Lupus is that treatment options remain limited and the understanding of the disease in terms of its onset and progression is also limited,” says Gulati, an assistant professor in the UC Division of Immunology, Allergy and Rheumatology and a UC Health physician. “The disease has a wide spectrum in terms of age distribution so it can also affect children or young adults who can have more severe manifestation and long-term damage from disease as it progresses over time.”

Lupus affects 1.5 million people in the United States and occurs in both men and women, though 90 percent of those diagnosed are women, with African-Americans disproportionately impacted by the disease, according to the Lupus Foundation of America. It can cause inflammation, swelling and damage to joints, skin, kidneys, blood, the heart and lungs and in severe cases Lupus can be fatal.

Gulati recently conducted a literary review of more than 100 research articles on Lupus and concludes that while there is a genetic predisposition for the disease, it is not the sole cause. His findings are available online in the scholarly journal Seminars in Arthritis and Rheumatism.

Researchers studying Lupus have identified a triad relationship of one’s genome or genetic background; epigenome or how genetic material is modified over a lifetime; and exposome, which refers to the environmental factors individuals are exposed to over time, says Gulati.

Gulati says a study looking at Lupus occurrence in identical twins found that clinical manifestation of the disease occurred in both siblings only 24 percent of cases. It’s more likely that genetic risk factors along with environmental influence play a pivotal role in Lupus development. Ultraviolet radiation from sunlight exerts toxic effects on the skin triggering flare-ups in Lupus symptoms, while particulate air pollution, especially from diesel vehicular exhaust, can also potentially worsen the condition.

“This is of particular interest in Cincinnati,” says Gulati. “We live in a city that is surrounded by many major roads and highways. There are several in our city and there is a huge amount of truck traffic which slows down allowing exposure to particulate air pollution even more.”

Gulati says trace elements–especially heavy metals–prevalent in the environment that can be triggers for Lupus. He says research in animal models indicates that many, including uranium, lead and cadmium, are capable of inducing autoimmunity.

It has been demonstrated that elements like mercury, nickel and gold have potentiate delayed hypersensitivity reactions in patients with connective tissue disease, notes Gulati in his manuscript. The resultant enhanced inflammation has been considered a pathogenic factor in exacerbations of autoimmune and inflammatory diseases including Lupus, which occurs in significantly higher rates among dental workers and others exposed to mercury.

Reproductive-age women are disproportionately impacted by Lupus, says Gulati, who cited a study in the United Kingdom that found an increased risk of Lupus in women using oral contraceptives. The hormonal influence in Lupus is also seen in exposure to xenoestrogens, natural or chemical components that imitate estrogen. Bisphenol A, (BPA) an environmental pollutant, is among the class of xenoestrogens that could be triggers for Lupus, says Gulati. It is used to make polycarbonate plastic and epoxy resins and is a common contaminant of many packaged foods and beverages.

Gulati offers some suggestions for Lupus patients to lessen some of the environmental factors that can trigger Lupus symptoms.

  • Regular follow-up with your rheumatologist for diagnosis and management of Lupus is vital to make early diagnosis and avoid long-term damage.
  • Avoid direct sunlight when possible. UV radiation can cause cells in the skin to die and cause Lupus flare-ups.
  • Always use sunscreen whenever there is a risk of being exposed to ultraviolet radiation. Using sunscreen even on cloudy days will lessen your risk of exposure.
  • Stop smoking. Cigarette smoking contains multiple triggers, including cadmium and polycyclic hydrocarbons, and can worsen Lupus symptoms.

Source: EurekAlert

Mental Health

May is Mental Health Awareness Day

May is Mental Health Awareness Day

 

In the United States, millions of Americans struggle with some kinds of mental health illness. 1 in 5 Americans experience some kind of mental illness and face several challenges over the course of their lifetime.
Around 70-90% of patients that seek proper treatment for mental illness see a reduction in their symptoms. This May join us in the movement to raise mental health awareness and #BeKindToYourMind.

 

*Depression is one of the leading causes of mental illness

* 18% of US adults live with a mental illness

* Anxiety is one of the most common illnesses in America

* 2.6% of Americans live with bipolar disorder

 

Source: MHA America, NAMI