Probiotics Prevent Autoimmune-Related Liver Injury

Evidence suggests that probiotics influence many systems in our bodies and prevent certain diseases. A recent study examined the effect of Lactobacillus probiotic strains on liver injury in lupus-prone mice, demonstrating that gut bacteria plays an important role in autoimmune diseases.

 

Probiotic is a term that describes helpful bacteria, which are normally found in human bodies. The most abundant source of probiotics in our bodies is in our gut, or intestines, where they help with digestion and processing of certain nutrients. Researchers have shown that gut bacteria can affect a range of diseases and bodily functions, such as depression, anxiety, our immune system, and even certain aspects of memory. Since our gut bacteria can have such wide-ranging effects, many groups are currently studying how we can alter the composition of gut bacteria to our advantage. Probiotics can be found in certain foods like yogurt and also in ingestible supplements. Clinical trial data suggests that supplements containing certain strains of bacteria have beneficial effects. However, a number of the many bacterial strains in our intestines have not been thoroughly studied. A recent report published in the British Journal of Nutrition assessed the effects of two different probiotics on lupus-prone mice.

Lupus-prone mice were fed a normal diet or a diet that contained one of two probiotic strains of used as intervention: Lactobacillus paracasei or Lactobacillus reuteri. The initial experiments showed that these two probiotics reduced characteristic liver damage that occurs as mice develop lupus. Additionally, researchers saw fewer immune cells and reduced inflammation of the liver in mice fed diets that contain probiotics. Lastly, they reinforced the previous result by examining the molecular pathways that cause liver damage as a result of lupus. They observed that in the livers of probiotic-fed mice, there was less activation of pathways that induce liver damage.

This study was the first to discover that treatment with Lactobacillus paracasei or Lactobacillus reuteri reduces liver damage and inflammation in lupus-prone mice. This has further implications in other immune disease models, since these probiotics may reduce inflammation on a broader scale. Additionally, this study provides a rationale to test the two strains of bacteria in a clinical trial to determine whether they have a positive effect on patients who are diagnosed with lupus or at a high-risk of developing lupus. The study of gut microbes and their effects on the human body is vastly expanding, providing insights into the crucial roles they play. As we expand our understanding of how bacteria influence the systems of the body, we open up the possibility of discovering novel therapeutic strategies for various disease states, particularly those of autoimmune origin.

SLE-Key Rule-Out Test for Lupus Is One Step Closer to Entering the Chinese Market

ImmunArray and Kindstar Global, two companies focused on the development and marketing of diagnostic tools for acute and chronic immune and neurodegenerative diseases, have joined forces to launch the cost-effective SLE-Key Rule-Out Test for lupus in China.

The blood test, which helps clinicians accurately rule out lupus during diagnosis, is expected to enter the Chinese market by November 2017. The process will be formally presented at the American College of Rheumatology 2017 Annual Meeting, held Nov. 3-8 in San Diego.

“This partnership with Kindstar combines the resources of two innovative diagnostic companies that are focused on finding solutions to the diagnosis of autoimmune diseases, and we are extremely excited about the possibilities that this alliance can afford both parties,” Donna Edmonds, CEO of ImmunArray, said in a press release.

With over 1 million patients diagnosed with lupus, China has the second largest incidence of this autoimmune disease worldwide.

Available in the United States since 2016, the SLE-Key is based on ImmunArray’s proprietary iCHIP platform, which detects circulating systemic lupus erythematosus (SLE)-related antibodies in blood samples. The test has shown to be highly sensitive and a powerful tool.

“The business relationship and expanded market opportunity this provides to Kindstar is an important part of our strategy to be the premier specialty laboratory in China,” said Shiang Huang, MD, founder and CEO of Kindstar. “We are focused on providing testing to a growing number of specialists as they support patient care. This expanded product line for rheumatologists is another demonstration of that commitment.”

Under the agreement, ImmunArray will provide training to Kindstar staff on the SLE-Key Rule-Out Test. Both companies will then evaluate ImmunArray’s blood-based diagnostic test using 500 blood samples from healthy volunteers and individuals in China with SLE symptoms.

Results of this analysis, together with previous clearance of the iCHIP platform by the China Food and Drug Administration (CFDA), are expected to provide the scientific and regulatory support required for bringing the SLE-Key Rule-Out Test to China.

The agreement also states that Kindstar will have exclusive marketing rights for ImmunArray’s SLE-Key Rule-Out Test in China.

The Lupus Research Alliance and Pfizer Descend into mHealth Studies

The movement in making studies more patient-centric continues, as we recently featured Amgen’s new mHealth study that’s measuring migraine outcomes in patients, and Pfizer is now implementing its own mHealth study in Lupus. Pfizer is collaborating with The Lupus Research Alliance, a private funder of Lupus research to build and implement a new mobile app using Apple’s Research Kit platform through a non-interventional clinical trial called VALUE (VAlidation in Lupus of an Electronic Patient Reported Outcomes Tool) through their LuCIN program . The custom smartphone app will enable lupus patients to report on their fatigue and other symptoms in real time. In this interview, Albert Roy, LuCIN’s Executive Director, will discuss the VALUE study and how it is impacting lupus patients with the help of the Lupus Clinical Investigators Network (LuCIN).

Moe Alsumidaie:  How did the collaboration between Pfizer and the Lupus Research Alliance on the mobile app start?Albert T. Roy

Albert Roy: The Lupus Research Alliance has a long history with Pfizer, as we have conducted research within their clinical therapeutics and innovation branch (CTI). Pfizer was looking at technology efforts for conducting clinical trials, and they mentioned they had a partnership with Apple and were using Apple’s Research Kit in a variety of disease indications. Knowing that Pfizer has developed a Research Kit framework, we thought there could be an opportunity to do a clinical study in Lupus. So, we started discussing appropriate steps to use the same framework to build a Lupus-specific app, and run a clinical study to improve outcomes collection for Lupus patients. The purpose of this app is to address how technology could facilitate patient reported outcomes in clinical research.

MA: What patient reported outcomes (PROs) is the Lupus study mobile app measuring, and how is the mobile app different than traditional PRO data collection methods if you’re collecting the same data?

AR: Studies in Lupus look at three instruments that determine a patient’s disease activity. One is by measuring certain aspects of how the patient is feeling on a global assessment range. The second instrument is the short-form 36, a health survey that has 36 questions to measure functional health and well-being from the patient’s point of view. It is a practical and reliable measure of physical and mental health. It can be completed in 5-10 minutes and it is a generic health survey that can be used across all diseases and treatment groups. The third instrument we wanted to look at is the patient global assessment. It is a visual analog scale from 0 to 10 and is based on an algorithm. The patient moves their finger along the scale based on how they are feeling and it calculates the score. The higher the score, the worse the disease and their global health. Traditional patient assessments in Lupus are unfortunately done in a very arcane way; it requires the patient to come to the clinic and complete a paper form. Lupus patients don’t come to the clinic every week unless they are very sick, so they have to recall weeks and weeks of how they felt and address the question in the most accurate way. We wanted to reduce this burden on the patients and see if we could translate all these instruments from paper into an electronic format. Running the mobile app is an opportunity for patients to do the assessment on their own, in the comfort of their homes and on a smartphone. We could get more accurate data since they would be able to answer these questions once or twice a week versus once a month. We could measure that against paper form submissions to see what would be more effective—Is the paper form just as good/worse/better than the electronic version?

MA: What functionality does the app provide that is an advantage over paper-based PROs?

AR: The app offers flexibility and convenience to patients. For example, with the SF 36, if you’re taking it on paper in the clinic, you have to finish 36 questions in a 5-10-minute timeframe before you see your doctor. There isn’t an opportunity to go back and think about or change your answers or take a break or take it home with you. On the app, you have the ability to complete the SF 36 with a longer and more flexible timeframe, so you do not need to answer all 36 questions at once. You can answer a few, then come back to it and pick up where you left off. You also can set alerts that remind you to complete the assessments. Another advantage is that the site will have the ability to remind the patient to complete their instruments.

MA: Are you collecting any additional data from patients other than the PROs (i.e., biometric data) through wearables?  How are you assuring data integrity and security on iPhones?

AR: There was some discussion about trying to link an Apple Watch for the study surveys and to collect biometric information; however, we discovered that it would get too complex because of the type of data that we are collecting, and due to the ethics and IRB issues at the institutions. We have capped the data being collected to be focused on these three PROs and not get into factors like the number of steps taken. The patient cannot use their own smartphone for the study; they are given a study-specific iPhone, which has texting, calling, and internet capabilities, but they will not be able to download additional apps due to data integrity. The only app that will be active on the iPhone is the app for the study.

MA: Can you describe LuCIN?

AR: LuCIN is a network made up of academic research centers that the Lupus Research Alliance has had a long-standing relationship with. Exclusively in North America, we have 59 sites—50 of which are in the United States—and nine are in Canada. We add value to the clinical trials process, specifically around recruitment of investigators and sites, and the design of clinical trials. We have Lupus experts and a significant number of patients that are within the Lupus network. Our studies run the gambit of the clinical trials from drug interventional trials, where the drugs were previously approved for another disease indication and are being repurposed for Lupus. We also look at non-drug interventional trials, such as using new technology like the Lupus app we just discussed for ePROs. We are looking at innovative imaging modalities assessing organ systems within Lupus patients, and are implementing non-repurposed drug trials with innovative therapies for Lupus. We have a pretty good portfolio of diverse trials and we are excited to get underway.

NKTR-358 Bolsters T-cells’ Response to Autoimmune Disorders Such as Lupus, Study Shows

NKTR-358 bolsters T-cells’ ability to respond to immune inflammatory disorders such as lupus, according to a preclinical-trial study.

Nektar Therapeutics said its therapy increased levels of a subset of T-cells known as regulatory T-cells and reduced inflammation. It also generated fewer side effects than immunosuppressant drugs.

The company presented the findings at the World Congress on Inflammation in London, which started July 8 and ended July 12. The presentation was titled “NKTR-358: a selective, first-in-class IL-2 pathway agonist which increases the number and suppressive function of regulatory T cells for the treatment of immune inflammatory disorders.

NKTR-358 targets the interleukin-2 (IL-2) receptor complex on the surface of regulatory T-cells, which are also known as Tregs. Those cells are responsible for keeping immune system responses under control. Their levels are lower, and they are less active, in several autoimmune disorders.

Researchers said NKTR-358 stimulated the growth and activation of Tregs, restoring their levels and correcting an imbalance in the mechanisms underlying autoimmune disorders.

A single injection ramped up Tregs’ activity in mice for seven to 10 days and in primates for more than 14 days, researchers said.

The team also said that NKTR-358 significantly suppressed inflammatory responses in mice with hypersensitive skin, and restored a more normal immune response in the animals. Results were similar in primates, researchers said.

In another experiment, the team administered NKTR-358 to mice with lupus for more than 12 weeks. The animals’ Treg numbers rose for a sustained period, and they had better kidney function.

“These studies show that NKTR-358 increases the suppressive capacity and prolongs activation and proliferation of regulatory T-cells with limited effects on conventional T-cells in order to address the imbalance found in many autoimmune diseases,” Dr. Jonathan Zalevsky, a senior vice president of Nektar Therapeutics, said in a press release.

“NKTR-358 also demonstrated suppression of antigen-driven inflammation in multiple preclinical models, including systemic lupus erythematosus,” he said. “We are very excited about NKTR-358’s potential as a resolution therapy in autoimmune disease.”

Nektar is evaluating NKTR-358 in a Phase 1 clinical trial with healthy volunteers. The main objective of the study is to determine an optimal dose for future trials. Researchers will also assess NKTR-358’s safety, stability and effectiveness.

The company plans an ascending-dose trial of the therapy in lupus patients starting in the second half of 2017.

Project encourages lupus patients to share life experiences

The national lupus patient advocacy community is encouraging people with lupus to participate in a project that lets lupus patients contribute to lupus drug development by sharing how the disease affects their daily lives.

Participants can share their experiences, concerns and views on new treatments by taking an online survey. That information will be shared with the Food and Drug Administration and pharmaceutical companies.

On Sept. 25, there will be a Lupus Patient-Focused Drug Development Meeting in Hyattsville, Md., that participants can attend in person or join via webcast. The meeting will be another opportunity for people with lupus to provide input on patient panels and during an open-comment period. The meeting is being organized by the Lupus and Allied Diseases Association, the Lupus Foundation of America, and the Lupus Research Alliance.

“Far too long have individuals with lupus have suffered greatly from the lack of adequate treatments, but through PFDD project they now have the extraordinary opportunity to sit at the table, share their unique viewpoints, and be heard by the FDA, “said Kathleen Arntsen, Lupus and Allied Diseases Association president/CEO. “We are thrilled to be a part of this remarkable and long-overdue initiative, and we strongly urge anyone living with this debilitating disease to act now by taking the survey to help advance new therapies in lupus.”

Jamesetta Smith, president of the Lupus Foundation of Arkansas, is encouraging lupus patients in Arkansas to participate.

“Let us show how many lupus patients are actually here in Arkansas wanting something done about this cruel, complex, devastating, debilitating disease lupus,” Smith said.

Blood Test to Detect Hardened Arteries Can Show Whether Lupus Patients Are Developing a Heart Disease

A biomarker of hardened arteries2 makes it eight times more likely that a lupus patient will develop a cardiovascular disease, according to a study.

The presence of the marker could prompt lupus patients with no symptoms of heart disease, or who appear to be at low risk of developing it, to take preventative measures against hardening of the arteries. The condition, which doctors call atherosclerosis, stems from an accumulation of fatty deposits, or plaque, in arteries.

The biomarker, known as High Sensitivity Cardiac Troponin T, or HS-cTnT, shows up in a blood test. Before the team introduces the test to doctors, they plan studies that verify its ability to detect atherosclerosis.

Researchers presented the results of the study at the annual European Congress of Rheumatology in Madrid, June 14-17.

None of the lupus patients in the study, nor the healthy controls, had any symptoms of cardiovascular disease. And all were at low risk of developing it, traditional tests indicated.

But researchers found signs of carotid fatty deposits in 36.5 percent of lupus patients — 23 out of 63. In contrast, only 11.1 percent — two out of 18 — of the healthy controls showed similar signs.

The research team concluded that only patients’ age and the level of their lupus were independently associated with the presence of carotid fatty deposits.

Eighty-seven percent of lupus patients with signs of carotid fatty deposits had the biomarker in their blood. That was true of only 42.5 percent of patients without signs, researchers said.

In addition, only 11.5 percent of patients with undetectable levels of the marker had carotid fatty deposits.

“The results of our study raise the possibility that this easily measured biomarker could be introduced into clinical practice as a more reliable way of evaluating CVD [cardiovascular disease] risk in lupus patients,” Karim Sacre of Bichat Hospital in Paris said in a press release. “This in turn will enable more effective primary prevention measures, such as treating abnormally raised blood lipids to be implemented,” added Sacre, the lead author of the study.

Better therapies have increased the life expectancy of lupus patients. But cardiovascular diseases have emerged as a major cause of death among them.

The blood test could increase the chance of early detection of atherosclerosis in lupus patients, a condition that traditional tests underestimate.

“Before introducing this new biomarker into clinical practice, we are conducting further research to confirm our findings on a larger cohort of patients, with a longer follow-up period, analyzing not only carotid plaques, but also the occurrence of major cardiovascular events,” Sacre said.

This Post Copyright Lupus News Today.

Older Lupus Patients Are More Prone to Developing a Form of the Disease Affecting Limbs, Study Reports

Older lupus patients may be at risk of developing a form of the disease that affects arms and legs, according to a study.

The most common manifestation of the peripheral nervous system form of system lupus erythematosus, known as PNS-SLE, is polyneuropathy, or damage to the nerves that control the arms, hands, legs and feet.

Researchers published their study in the journal Autoimmunity Reviews. It was titled “Peripheral nervous system involvement in systemic lupus erythematosus: Prevalence, clinical and immunological characteristics, treatment and outcome of a large cohort from a single centre,

Lupus can affect either the central nervous system or the peripheral nervous system. The central nervous system form is called CNS-SLE. Poor quality of life and higher death rates are associated with PNS-SLE, but little is known about the condition.

To learn more, researchers analyzed the records of 524 lupus patients at a medical facility in Barcelona between March 2014 and December 2015. They wanted to know how many patients had PNS-SLE, treatment methods doctors used and patient outcomes, and variables that could be associated with the form.

Ninety-three patients, or 17.7 percent, had PNS-SLE. Ninety were women. The women’s mean age of diagnosis was 44.8 years, and the average time between a woman being diagnosed with lupus and PNS-SLE was 88 months.

Almost 37 percent of the PNS-SLE patients complained of polyneuropathy. Twenty-four percent had non-compression mononeuropathy, a condition in which a single nerve is damaged. Seven and a half percent had cranial neuropathy, or damage to the nerves in the head. Another 7 1/2 percent had myasthenia gravis, a condition marked by muscle weakness. And 1 percent had Guillain-Barré syndrome, an autoimmune disorder in which the body attacks its own nerves.

Electrodiagnostic tests indicated that 49 patients, or 80.3 percent, had experienced axonal loss. Axons are neuron, or nerve cell, components that pass electrical signals to other neurons.

Doctors had treated 36 patients out of the 90, or 40 percent, with glucocorticoids, immunosuppressant drugs, or a combination of the two. More than 77 percent of the patients had achieved a complete or partial response to treatment, regardless of the kind of PNS-SLE they had.

In addition, the analysis showed that patient who were older when they received a lupus diagnosis and who had no blood-related lupus symptoms were more prone to develop PNS-SLE than other patients.

“PNS‐SLE involvement is not uncommon and sensory‐motor axonal polyneuropathy is the most frequent manifestation,” researchers wrote. “It occurs more frequently in patients who are diagnosed with SLE at older age.”

The team said “studies are needed to establish the true incidence of PNS‐SLE syndromes and the role” that hematological, or blood-related, factors play in the development of this form of lupus.

This Post Copyright Lupus News Today.

Cause of Neuropsychiatric Ills Common to Lupus Seen in Study, Potential Treatment Raised

Neuropsychiatric symptoms in people with systemic lupus erythematosus may be caused by increased levels of the inflammatory molecule interferon-alpha in their brains, according to a study published in the journal Nature. But a treatment now in clinical trials may be able to arrest the processes that lead to those symptoms.

The inflammatory molecule appears to activate microglial cells in the brain, and these cells, in turn, destroy synapses (structures that support communication between neurons) — at least, that was the process seen in a mouse model of lupus. But the research team from Boston Children’s Hospital also found increased interferon activity in patients’ brains, suggesting the same process might be going on in people lupus.

“In general, lupus patients commonly have a broad range of neuropsychiatric symptoms, including anxiety, depression, headaches, seizures, even psychosis,” Allison Bialas, PhD, the study’s first author, said in a press release. “But their cause has not been clear for a long time; it wasn’t even appreciated that these were symptoms of the disease.”

To study the impact of autoimmune processes on neuropsychiatric lupus, the team used a mouse model of the disease in which the immune processes depend on signaling through the interferon-alpha receptor 1 (IFNAR). Researchers know that this type of immune signaling is found in 50% to 80% of all lupus patients.

Like many lupus patients, the mice showed signs of psychiatric disease. They were anxious, had a poor cognition, and were aggressive in social settings.

Injecting mice with labeled interferon — so it could be tracked — the researchers discovered that it entered the brain in sufficient quantities to elicit a response. Their report, “Microglia-dependent synapse loss in type I interferon-mediated lupus,” describes how the team used advanced microscopic techniques to catch the activated microglia in action.

Microglia are the brain’s main immune cell. They can release inflammatory factors of their own, but also clear the brain of pathogens or cell debris. The team could see how the microglia engulfed synapses, causing the animals to lose a significant amount of synapses in the frontal cortex part of their brains.

But treating the mice with an anti-IFNAR drug, called anifrolumab, prevented synapse loss. Researchers also noted that the treatment reduced their behavioral abnormalities.

Anifrolumab is currently in Phase 3 clinical trials in lupus, and the team’s data suggest that the drug might have the potential to prevent neuropsychiatric symptoms in lupus. Patients with severe, active neuropsychiatric lupus are, however, excluded from these trials, so future studies will be needed to evaluate the drug’s effectiveness in these people.

The researchers believe the findings likely will affect research into lupus and other diseases, particularly since inflammation is present in numerous other conditions.

“We’ve found a mechanism that directly links inflammation to mental illness. This discovery has huge implications for a range of central nervous system diseases,” said Michael Carroll, PhD, the study’s senior author.

“We’ve seen microglia dysfunction in other diseases like schizophrenia, and so now this allows us to connect lupus to other CNS [central nervous system] diseases,” Bialas added. “CNS lupus is not just an undefined cluster of neuropsychiatric symptoms, it’s a real disease of the brain and it’s something that we can potentially treat.”

 

This Post Copyright Lupus News Today.

Upcoming Events

Support Group Meeting in Pensacola

Join us on July 22, 2017

at 11:00 at the Lupus Office at 

1108 Airport Blvd. Pensacola FL 

Support groups provide information, support, and friendship in a comfortable, non-judgmental atmosphere

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The Lupus Support Network joins with The Lupus Foundation of Florida

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Photos From The First Meeting Of The Florida Lupus Action Team

 

 

 

 

 

 

 

 

Intro

Questions

1- Could you have lupus?

2- Do you know the signs and symptoms of lupus?

3- Do you know what questions to ask your physician?