This video is about 10 inspiring celebrities with Lupus based on entertainment news reports. In this video, we’re featuring the top 10 inspiring celebrities living with lupus. From singers to athletes to journalists, these celebrities are living proof that anything is possible when you have a positive outlook. Check out this video if you’re looking for celebrity news that inspires you! These celebrities have paved the way for others with lupus, proving that anything is possible if you decide. Watch and learn how they’ve overcome obstacles and succeeded despite living with a disease affecting many parts of life.
Many autoimmune diseases, including lupus, have been linked to problems with the toll-like receptors (TLR) on immune cells, in particular the TLR7 and TLR8 receptors, which recognize the nucleic acids in RNA from invading viruses and bacteria. While TLRs are critical to mobilizing the body’s immune defences against these invaders, if they are out of tune, they can activate the immune system against the body’s own nucleic acids, leading to painful symptoms. Researchers at UC Berkeley have shown that mutations in the UNC93B1 gene, which regulates TLRs, are associated with autoimmune symptoms in mice and humans. CREDIT Victoria Rael and Gregory Barton, UC Berkeley
Lupus is a lifelong, often painful and occasionally lethal autoimmune disease. Few treatments exist today beyond powerful steroids to knock down a patient’s immune system — a therapy that has its own serious risks.
The good news is that new and promising treatments are in clinical trials. But the term lupus belies the fact that the disease has a variety of causes, which means that treatments will have to be highly personalized to guarantee that each patient is given the drug that targets the specific genetic mutation responsible for their variety of lupus.
Researchers are just now beginning to link specific genetic mutations to subsets of lupus patients, allowing physicians to target therapies to those who will benefit most. In the latest advance, researchers at the University of California, Berkeley, report in a new paper the discovery of two sets of patients with genetic mutations that are nearly identical to mutations that the researchers had earlier pinpointed in mouse and cell lines as linked to autoimmune disease.
These two genetic links are among several dozen mutations that the UC Berkeley team recently discovered and linked to lupus, all in one gene that regulates a prime suspect in a subset of lupus patients — proteins called toll-like receptors (TLR), which enable immune cells to recognize foreign DNA and RNA.
According to study leader Gregory Barton, UC Berkeley professor of molecular and cell biology, identifying these mutations could help doctors deliver a personalized treatment to patients with oversensitive TLRs and, in particular, oversensitive TLR7 receptors.
“We basically have a map now,” said Barton, an investigator in the Howard Hughes Medical Institute. “It’s not like everybody with lupus has a gene mutation that causes overactivation of TLRs and TLR7. But drugs are coming online that very specifically inhibit TLR7. As we sequence more and more people, it will become easier to identify those patients and put them on those drugs. That’s a lot better than the current course of therapy for lupus, which is brutal.”
“This is exciting because the drug will be orally available and is in clinical trials now,” said Victoria Rael, a UC Berkeley graduate student who, with fellow graduate student Julian Yano, is a co-first author of the paper.
The results of the genetic screens and details of the patients’ mutations were published today (May 23) in the Journal of Experimental Medicine.
A problem recognizing ‘self’
Autoimmune diseases, which range from rheumatoid arthritis and Crohn’s disease to scleroderma and numerous thyroid conditions, stem from attacks by the immune system on the body’s own cells that destroy normal, healthy tissue.
Many studies have linked at least two types of autoimmune disease, lupus and psoriasis, to TLRs, which are part of the innate immune system that initially detects foreign invaders, such as viruses and bacteria, and stimulates a first line of attack. Normally, TLRs are delicately tuned to react only to foreign DNA and RNA, but if that tuning is off, they can react to a body’s own nucleic acids and proteins associated with nucleic acids, which look much like those of pathogens.
What makes this autoimmune reaction so deadly is that the TLRs also activate the body’s second-line defense, the more powerful adaptive immune response, mobilizing T and B cells, macrophages, and other cells. These cells then mount a sustained attack that destroys the body’s healthy tissue and causes chronic inflammation.
The most common form, systemic lupus erythematosus (SLE), for example, is characterized initially by skin rashes — in particular, a butterfly-shaped rash on the face — but later by damage to joints, muscles, organs and skin, causing pain and fatigue. It’s most commonly seen in females, often starting during the teen years. Lupus, in general, is two to three times more prevalent among women from many ethnic and racial minority groups than among white women.
“We think the way the system works is that if nucleic acids find these receptors, most likely they’re going to be from a virus,” Barton said. “But in some people, the receptor is more responsive, so now levels of self-nucleic acids that otherwise wouldn’t stimulate the receptor in a normal person activate the receptor. We think that one of the ways that these mutations are working is that they’re making levels of self-nucleic acids that normally wouldn’t be stimulatory, stimulatory.”
Barton and his lab colleagues have been investigating the role of TLRs that are misregulated in lupus, and in particular, one of the main proteins that regulates them: UNC93B1, or UNC for short. Several years ago, a team of postdoctoral fellows and graduate students in his lab screened in cell culture more than 100 genetic mutations in the UNC gene to see which ones overstimulated TLRs and would be good targets for further study. While they published some details in earlier papers, they didn’t publish the complete list because there seemed to be little point — almost no data was available on the genome sequences of lupus patients to compare with the mutations that overstimulated TLRs.
But that has changed in recent years, thanks to a plunge in the cost of genome sequencing. That’s how the mother of a young girl with severe autoimmune disease found Barton. Her daughter’s DNA had been sequenced and showed a mutation in a region of UNC that Barton’s team had noted in an earlier paper.
Lupus in the family
Rael and undergraduate Madeleine Weiss used the same cell culture screening technique to test the novel mutation from the young girl and found that it had an overstimulating effect, similar to the effect of other mutations in that area of the UNC gene. Surprisingly, the patient had the genetic mutation on only one of the two UNC alleles, meaning that she had one normal UNC gene, yet she still suffered severe autoimmune symptoms.
Barton and his team also connected with a family of five afflicted with lupus. All had mutations on one UNC allele in another area of the UNC protein that Barton’s team had previously identified. That mutation, when screened in cell lines, also produced overactive TLRs.
“We were skeptical that just one copy of a gene would be sufficient to cause a disease,” Rael said. “It wasn’t until we put the patients’ mutations into cell lines and saw that they led to very convincing TLR hyper-responsiveness that we realized they had the possibility of being sufficient to be disease-causing.”
Rael and Yano then repeated the screening work previously performed in the lab and confirmed that 32 distinct mutations in the UNC gene — about one-third of the mutations tested — increased the sensitivity of TLR7 to nucleic acids at least twofold. About another five mutants increased TLR7 sensitivity but to a lesser degree. Before these screens, only two mutations in the UNC protein had been linked to increased sensitivity of TLR7 in mice, though three additional human mutations were reported within the last two months.
Barton is hopeful that by publishing the complete list of TLR hypersensitivity mutations, doctors can identify other lupus patients who could benefit from the anti-TLR drugs now in clinical trials. One drug, M5049, or Enpatoran, appears to work by latching onto two human receptors, TLR7 and TLR8, and preventing them from binding nucleic acids.
Rael, Yano and other members of Barton’s lab are investigating further how these unique UNC mutations affect the way a patient manifests the disease. They have recreated these patients’ mutations in mice so that they can model human lupus.
“With mouse models, you can start thinking about how, even though the mutations are in the same protein, the different mechanisms of TLR regulation break down, which immune cells get activated as a result, and how this can lead to differences in the symptoms patients suffer from,” Rael said.
The lab also is trying to understand how UNC tunes TLRs, which may be by regulating the number and arrangement of TLRs on immune cells. More TLRs may make a person more sensitive to the small number of self-nucleic acids circulating in the body.
“UNC93B1 is important for getting the receptors to the place where they can function, but it also is important for regulating them when they get there,” Barton said. “The protein is a very baroque way of trying to make decisions about whether the nucleic acid that you just bound to a TLR is from a virus or from one of your own cells.”
He hopes that physicians add this gene to the list of lupus-associated genes, “so if they see a mutation like these, even a heterozygous mutation, they will investigate further.”
A new study details the high-throughput process for rapid screening and identification of mysterious long non-coding RNA.
UC Santa Cruz researchers have discovered that LOUP is a multifunctional gene in immune cells called monocytes. LOUP can work inside the nucleus to control its neighbour SPI1. They also discovered that LOUP RNA can leave the nucleus and produce a small peptide in the cytoplasm leading to an increase in the protein SPI1 and causing downregulation of NF-kB, the master controller of inflammation. CREDIT Carpenter Lab, UC Santa Cruz
UC Santa Cruz researchers have discovered a peptide in human RNA that regulates inflammation and may provide a new path for treating diseases such as arthritis and lupus. The team used a screening process based on the powerful gene-editing tool CRISPR to illuminate one of the biggest mysteries about our RNA–the molecule responsible for carrying out genetic information in our DNA.
This peptide originates within a long non-coding RNA (lncRNA) called LOUP. According to the researchers, the human genome encodes over 20,000 lncRNAs, making it the largest group of genes produced from the genome. But despite this abundance, scientists know little about why lncRNAs exist or what they do. This is why lncRNA is sometimes called the “dark matter of the genome.”
The study, published May 23 in the Proceedings of the National Academy of Sciences (PNAS), is one of the few in the existing literature to chip away at the mysteries of lncRNA. It also presents a new strategy for conducting high-throughput screening to rapidly identify functional lncRNAs in immune cells. The pooled-screen approach allows researchers to target thousands of genes in a single experiment, which is a much more efficient way to study uncharacterized portions of the genome than traditional experiments focusing on one gene at a time.
The research was led by immunologist Susan Carpenter, a professor and Sinsheimer Chair of UC Santa Cruz’s Molecular, Cell, and Developmental Biology Department. She studies the molecular mechanisms involved in protection against infection. Specifically, she focuses on the processes that lead to inflammation to determine lncRNAs’ role in these pathways.
“Inflammation is a central feature of just about every disease,” she said. “In this study, my lab focused on determining which lncRNA genes regulate inflammation.”
This meant studying lncRNAs in a type of white blood cell known as a monocyte. They used a modification of the CRISPR/Cas9 technology, called CRISPR inhibition (CRISPRi), to repress gene transcription and find out which of a monocyte’s lncRNA plays a role in whether it differentiates into a macrophage—another type of white blood cell that’s critical to a well-functioning immune response.
In addition, the researchers used CRISPRi to screen macrophage lncRNA for involvement in inflammation. Unexpectedly, they located a multifunctional region that can work as an RNA and contain an undiscovered peptide that regulates inflammation.
Ms Carpenter said that understanding that this specific peptide regulates inflammation gives drugmakers a target to block the molecular interaction behind that response to suppress it. “In an ideal world, you would design a small molecule to disrupt that specific interaction instead of targeting a protein that might be expressed throughout the body,” she explained. “We’re still far from targeting these pathways with that level of precision, but that’s definitely the goal. There’s a lot of interest in RNA therapeutics right now.”
A new study shows certain combinations of antiviral proteins are responsible for lupus symptoms and affect treatment outcomes.
In a new study, researchers from Johns Hopkins Medicine say they have uncovered insights into why lupus symptoms and severity present differently in individuals with the autoimmune condition, which affects up to 1.5 million Americans. The team says this is a crucial step forward in understanding the biological mechanisms behind lupus and may also lead to shifts in how clinicians treat patients with the condition.
The full report concludes that specific combinations and elevated levels of immune system proteins, known as interferons, are associated with certain lupus symptoms such as skin rashes, kidney inflammation and joint pain. Interferons normally help to fight infection or disease but are overactive in lupus, causing widespread inflammation and damage. The study also shows that other common lupus-related symptoms cannot be explained by increased interferon levels.
“For years, we have accumulated knowledge that interferons play a role in lupus,” says corresponding author and rheumatologist Felipe Andrade, M.D., Ph.D., associate professor of medicine at the Johns Hopkins University School of Medicine. He says this research began with questions about why certain lupus treatments were ineffective for some patients. “We have seen instances where the patient surprisingly didn’t improve — we wondered if certain interferon groups were involved.”
Some lupus treatments are designed to suppress a specific group of interferons known as interferon I. In clinical trials for these treatments, the team observed some patients failing to improve despite genetic tests showing high interferon I levels before treatment, or what experts call a high interferon signature. The team believed that two other interferon groups, interferon II and interferon III, may be to blame for these poor treatment responses.
To investigate, the team looked at how different combinations of interferon I, II or III, and their overactivity, may present in people with lupus. Researchers took 341 samples from 191 participants to determine the activity of the three interferon groups and used human cell lines engineered to react to the presence of each specific interferon group to analyze the samples. Through this process, researchers determined that the majority of participants fell into four categories: those only with increased interferon I; those with a combination of increased interferons I, II and III; those with a combination of increased interferons II and III; or those with normal interferon levels.
Researchers could use these findings to make several associations between these interferon combinations and lupus symptoms. In those with elevated interferon I, lupus was mainly associated with symptoms affecting the skin, such as rashes or sores. Participants with elevated levels of interferon I, II and III exhibited the most severe presentations of lupus, often with significant damage to organ systems, such as the kidneys.
Not every symptom of lupus was associated with elevated interferons, though. The formation of blood clots and low platelet counts, which also affect clotting, were not associated with increased levels of interferon groups I, II, or III. Researchers say this indicates that interferon-dependent and other biological mechanisms are involved in this complex disease. The study also found that genetic testing of genes associated with these interferon groups, or the interferon signature, did not always indicate elevated interferon levels. They plan to investigate this in future studies.
“What we’ve seen in our study is that these interferon groups are not isolated; they work as a team in lupus and can give patients different presentations of the disease,” says rheumatologist Eduardo Gómez-Bañuelos, M.D., PhD, assistant professor of medicine at the Johns Hopkins University School of Medicine and the study’s first and additional corresponding author. Evaluating a patient’s elevated interferon combinations allows for a better understanding of how they may react to treatments and would allow clinicians to group them into clinical subtypes of lupus, Gómez-Bañuelos explains.
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