كودكان مبتلا به  پسوريازيس احتمال چاقي بيشري دارند 

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The largest study of physician-treated children with psoriasis around the world shows children with the skin disease are about twice as likely to be overweight or obese as children who don’t have the disease, according to new Northwestern Medicine research.

And US children with psoriasis have much higher odds than psoriatic children in other countries of being obese or overweight.

In the US, children with psoriasis had four times the odds of being overweight or obese as healthy controls. Within this US population, Hispanics and African American children had significantly greater rates of being obese and overweight than whites and Asians. The odds ratio of being obese were particularly high for U.S. children with more severe psoriasis (7.6).

“There has been increasing attention to the association of psoriasis and metabolic risks in adults, but this study shows that the association of being overweight or obese and having psoriasis may be even higher in affected children than in adults,” said Amy Paller, M.D., chair of dermatology at Northwestern University Feinberg School of Medicine and lead author of the study. She also is a pediatric dermatologist at the Ann and Robert H. Lurie Children’s Hospital of Chicago.

The paper was published Nov. 19 in Archives of Dermatology.

“This is incredibly significant,” Paller said. “It tells us these children are at increased risk of health complications (cardiac risk and insulin resistance) and need to be watched closely and treated.”

The study included 614 children five to 17 years old from nine countries in the Americas, Europe and Asia.

Previous studies showing an association between psoriasis and obesity were largely based on registry data, which is less precise and may under identify cases because of the reliance on diagnosis codes rather than a direct examination and measurements to calculate Body Mass Index.

In this study, about 30 percent of the affected children had an immediate family member with psoriasis, suggesting a strong genetic component. However, the reported family history of obesity was not higher in children with psoriasis than in control children.

“Perhaps our U.S. environment of eating more calories and getting less exercise along with a strong genetic component for the disease hikes the risk,” Paller said.

“There is something in the genetic makeup of these kids that predisposes them to these metabolic issues and positions psoriasis as a metabolic disorder,” noted Paller, also the Walter J. Hamlin Professor of Dermatology at the Feinberg School. “Psoriasis is driven by many of the same cytokines (proteins) that drive insulin resistance and being overweight.”

Psoriasis is characterized by red, often itchy scaling lesions that can be localized (especially to the scalp, knees and elbows) or cover the entire body. The disease affects 2.5 to 3.5 percent of the global population with up to 33 percent of the cases starting in childhood, particularly during adolescence.

“It’s a highly visible disease which can be devastating during the all-important years of psychosocial development of childhood and adolescence,” Paller said. “It affects their social life and even their ability to participate in sports. Psoriasis has a profound effect on children’s quality of life.”

The study also looked beyond the commonly used Body Mass Index (BMI) to investigate psoriasis’ link to central adiposity (fat around the waist) and the waist-to-height ratio, both of which are believed to have a higher correlation with metabolic risk. Internationally, the odds ratio of having a high waist-to-height ratio that imparted a high level of cardiac risk was 3.1 for all children with psoriasis and 4.1 for those with severe psoriasis.

“The bottom line is these kids need lifestyle intervention,” Paller said. “You can’t just treat psoriasis. You’ve got to work with these kids to increase exercise and decrease their caloric intake to reduce their risk for metabolic diseases. Perhaps losing weight could help their psoriasis as well.” Previous studies in adults have suggested that weight loss can result in less severe symptoms.

A question not yet answered is which comes first, the psoriasis or the excess fat? Is a high BMI the precursor of psoriasis in children or does the disease lead to an increased BMI through chronic cytokine release from psoriatic tissues, compounded by a lifestyle that may contribute to excess fat? Paller is currently investigating that question.

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The above post is reprinted from materials provided by Northwestern University. The original item was written by Marla Paul. Note: Materials may be edited for content and length.

بيماران پسوريازيس شديد دو برابر احتمال ابتلا به ديابت دارند

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An analysis of 27 studies linking psoriasis in 314,000 individuals with diabetes has found strong correlation between the scaly skin rash and the blood sugar disorder that predisposes patients to heart disease, say UC Davis researchers who led the review.

The findings appear in the Archives of Dermatology.

“Our investigation found a clear association between psoriasis and diabetes,” said April Armstrong, assistant professor of dermatology at UC Davis and principal investigator of the study. “Patients with psoriasis and their physicians need to be aware of the increased risk of developing diabetes so that patients can be screened regularly and benefit from early treatment.”

Psoriasis is a common skin problem that tends to run in families. It causes a raised red, flaky and sometimes itchy rash, often on the elbows and knees, although it can appear anywhere. It is believed to be an autoimmune disease, in which the body regards its own skin as foreign and mounts an inflammatory response.

Armstrong and her colleagues combined data from 27 observational studies of patients with psoriasis, in what is known as a meta-analysis. Five of the studies assessed the incidence of diabetes — that is, how many patients with psoriasis developed diabetes during the course of a study, which ranged from 10 to 22 years. The other studies assessed the prevalence of diabetes — how many patients already had diabetes at the outset of a study. Altogether, the studies evaluated more than 314,000 people with psoriasis and compared them to 3.7 million individuals (controls) without the disease.

Some of the studies classified patients by disease severity. The aggregate data for these studies showed that patients with mild psoriasis are over 1.5 times more likely to have diabetes than the general population while those with severe disease are nearly twice as likely. Among studies that assessed incidence, patients with psoriasis had a 27 percent increased risk of developing diabetes compared with the general population.

All but one study analyzing incidence found a link between psoriasis and diabetes. These studies included patient data from outpatient clinics, insurance claims and hospitals. Diabetes rates were similar in patients despite ethnicity or country where the study was conducted.

“The large sample size and consistent association between psoriasis and diabetes make these study findings very strong and suggest an underlying physiological link between the two diseases,” said Armstrong, who directs the Dermatology Clinical Research Unit at UC Davis and the teledermatology program.

While additional research is need to understand how the two diseases are associated, Armstrong believes altered immune pathways may make psoriasis patients more susceptible to developing diabetes.

“There is evidence that fat cells in psoriasis patients may not function normally,” she said. “These cells secrete inflammatory substances known as cytokines that increase insulin resistance in the liver and muscle and initiate destruction of insulin-producing cells in the pancreas.”

Additional research will also clarify other potential limiting factors in the current study. For example, the study’s authors noted that epidemiological or observational studies can be susceptible to confounding factors, such as concurrent medications used to treat psoriasis that may modulate the risk of developing diabetes.

Armstrong’s study adds to a growing body of research that shows psoriasis is not just skin deep. “We know patients with psoriasis and hypertension tend to require more aggressive therapy to bring their blood pressure under control,” said Armstrong. “We also know that psoriasis patients have higher rates of heart attacks, strokes and cardiovascular-related deaths than the general population. Primary-care physicians need to be aware of these underlying predispositions to disease to provide the best care to their patients.”

Armstrong and her colleagues plan to examine endothelial cells — cells that line blood vessels — to better understand the underlying physiological basis of psoriasis. They also are collaborating with other research institutions to develop a network to share clinical data on patients with psoriasis.

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The above post is reprinted from materials provided by University of California – Davis Health System. Note: Materials may be edited for content and length.

آفتاب تابستان براي بهبود پسوريازيس مفيد است. 

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Sun exposure is usually discouraged due to harmful rays causing skin cancer and premature aging but for the 7.5 million Americans suffering from psoriasis, the sun is a natural medication. “The sun is one of the best treatments for psoriasis, so in summer I encourage my patients to sit out on the deck and give their affected areas a good sun bath,” said Julie Moore, M.D., dermatologist at Gottlieb Memorial Hospital, part of Loyola University Health System. “30 minutes is adequate to improve the skin; you do not need to sit out for hours.” The ultraviolet rays in the sun are beneficial to the irritated skin.

Psoriasis is caused when the immune system mistakes normal skin cells for pathogens and reacts by creating an overproduction of skin cells. “Psoriasis is the most prevalent autoimmune disease in America,” says Moore. “There is no cure for psoriasis and it is a life long condition that flares up and calms down due to stress and environmental factors.”

Total direct and indirect health care costs of psoriasis for patients are calculated at $11.25 billion annually, with work loss accounting for 40 percent of the cost burden, according to the National Psoriasis Foundation. Approximately 60 percent of psoriasis patients missed an average of 26 days of work a year due to their illness.

“Psoriasis is much more than a cosmetic concern; it is often painful, difficult to heal and can be disfiguring,” says Moore, who has practiced dermatology for more than 20 years in the Chicago area.

Dr. Moore has the following facts about psoriasis to share:

• Sufferers of psoriasis cannot tolerate “live” vaccines such as the nasal flu vaccine and the shingles shot. Patients with psoriasis should always consult their physician or dermatologist before getting vaccinated.

• Psoriasis can occur anywhere on the body from the scalp to the bottoms of the feet and even under fingernails and toenails.

• Psoriasis is often the most stubborn on hands and feet. One of Dr. Moore’s most troublesome cases was an older gentleman. “He had severe psoriasis on his thumb and the top of his index finger, exacerbated by regular use of a lighter when igniting his pipe,” said Moore. “Hands and feet are in constant use and subject to friction from movement which aggravates already sensitive skin.”

• “Although it is natural to want to “pick” off the scaling or rough patches caused by psoriasis, this is actually one of the worst things you can do,” says Moore. “There are many creams that are excellent at dissolving “crusting” and promoting healing.”

• Contrary to popular belief, psoriasis does not always itch or even produce symptoms such as the telltale rash.

“Psoriasis has a strong genetic link and if both parents have it, the child has a 50 per cent chance of having it,” says Moore. “If one parent has it, the child has a 10 percent chance of having psoriasis.”

In addition to sunlight, treatment includes medication, creams and artificial light exposure.

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The above post is reprinted from materials provided by Loyola University Health System. Note: Materials may be edited for content and length.

درمان جديد براي پسوريازيس

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Three per cent of the world’s population suffer from the skin condition known as psoriasis. A Norwegian research-based company is close to developing a treatment that could help millions. The research may also prove beneficial in the treatment of other illnesses.

The psoriasis treatment consists of a compound which, when applied to the skin, is absorbed by skin cells much more naturally than most other ointments. It contains a synthesised molecule based on the fatty acid docosahexaenoic acid (DHA) which may prove effective in inhibiting chronic inflammation associated with psoriasis.

Clinical trials soon underway

Avexxin, a Trondheim-based company, is to begin clinical testing of the ointment in early 2013. If the results are positive, Avexxin may find itself on the cusp of an international breakthrough.

Successful tests of the psoriasis compound could also give an important boost to the pursuit of more comprehensive clinical trials to determine whether the technology can be applied to other chronic inflammatory conditions such as rheumatoid arthritis and nephritis, an inflammation in the kidneys.

Combining clinical phases 1 and 2A

Clinical trials often extend over a long period of time. The treatment must first be tested for toxicity on healthy volunteers. Subsequent trials must be carried out on real patients to ensure that the treatment has the desired effect. With an ointment such as this, which is to be applied externally, it is possible to combine trial phases 1 and 2A.

“This enables us to save a lot of time,” explains Professor Berit Johansen of the Norwegian University of Science and Technology (NTNU). Dr Johansen has been studying the mechanisms behind inflammatory disease since the end of the 1980s. She launched the company, Avexxin, in 2005.

Potential for treating other conditions

Two Avexxin projects have received funding under the programme for User-driven Research-based Innovation (BIA) at the Research Council of Norway:

  • Development of mechanism based, novel anti-inflammatory compounds (2006-2009)
  • Expanding drug pipeline in Avexxin — adopting new chemistry (2009-2012)

“We have been lucky in obtaining private funding that supports our main focus — the development of a medicine for treating psoriasis,” Dr Johansen explains.

“The financial support we have received from the Research Council has been critical to our research and has enabled us to develop several molecules to treat other inflammatory conditions with the same treatment target as psoriasis. These molecules could prove effective in treating rheumatoid arthritis and nephritis,” Dr Johansen states.

“When we carried out tests in summer 2012 to see whether one of the new molecules might have any effect on arthritis in animals, the results were extremely encouraging.”

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The above post is reprinted from materials provided by The Research Council of Norway. Note: Materials may be edited for content and length.

٢٠٠ اپليكيشن موبايل براي بيماري هاي پوستي

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A surge of mobile apps related to dermatology has allowed scores of smart phone users to track and diagnose a wide range of skin diseases but doctors are urging caution, according to a study published today in the Journal of the American Medical Association.

“There are 229 dermatological applications out there and most are free,” said Robert Dellavalle, MD, PhD, MSPH, senior author of the study and Associate Professor of Dermatology at the University of Colorado School of Medicine. “Yet this is an area of buyer beware because there are no regulations and no guarantees that these apps are providing accurate medical information.”

The study found mobile applications for monitoring psoriasis, connecting people with patient organizations, diagnosing melanoma, dispensing sun screen advice, dermatology education and skin medications.

Self-surveillance/diagnosis apps vary widely in capabilities. Some allow patients to document lesions, upload and receive dermatologist or algorithm-based feedback about the malignancy potential of lesions, follow diagnosis algorithms and log personal treatment regimens.

Others are focused on a single malady like acne, rosacea, psoriasis or eczema. Patients and doctors can interface on apps and one lets users get pathology results from their phone. Another, Dr. Mole, allows users to photograph a mole and monitor its changes over time to determine if it’s cancerous.

The 10 most reviewed apps included:

  1. Ultraviolet-UV Index
  2. VisualDx
  3. SPF
  4. iSore
  5. SpotMole
  6. Pocket Derm
  7. Skin Scan
  8. Doctor Mole
  9. What’s My Rash?
  10. Skin Conditions

The U.S. Food and Drug Administration announced Monday that it would only regulate the small number of apps that act like medical instruments, those that perform ultrasounds or other procedures.

Dellavalle, Chief of Dermatology at the Denver Veterans Affairs Medical Center, said the rise in medical apps in general and dermatology in particular offers the chance to expand care into rural and underserved populations.

They may also help mitigate the shortage of dermatologists nationwide. Still, he urged people to use common sense.

“There is a huge expansion of medical apps across all disciplines now. This will require some caution by users but it also opens up new opportunities,” he said. “I think most apps are generally safe right now, but I would not rely solely on them. I would cross-reference them with other apps, other people and with your doctor.”

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The above post is reprinted from materials provided by University of Colorado Denver. Note: Materials may be edited for content and length.

بيماران پسوريازيس در معرض بيماري هاي بيشتري هستند 

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Patients with mild, moderate and severe psoriasis had increasingly higher odds of having at least one major medical disease in addition to psoriasis, when compared to patients without psoriasis. Reporting findings in JAMA Dermatology, researchers from the Perelman School of Medicine at the University of Pennsylvania, concluded that the severity of disease, as measured by the percentage of body surface area affected by psoriasis, was strongly linked to an increased presence of other diseases affecting the lungs, heart, kidneys, liver and pancreas.

The research is part of the landmark Incident Health Outcomes and Psoriasis Events (iHOPE) Study. The investigators surveyed general practitioners caring for 9035 psoriasis patients — 52 percent with mild disease, 36 percent with moderate disease, and 12 percent with severe disease affecting more than 10 percent of their body surface area. Significant associations were found between psoriasis and a range of diseases, including chronic pulmonary disease (COPD), diabetes, mild liver disease, myocardial infarction and peripheral vascular disease, peptic ulcer disease, renal disease and other rheumatologic diseases.

“As we identify additional diseases linked to psoriasis, patients and physicians need to be aware of the increased odds of serious co-morbid illnesses, which is especially important in severe cases,” said senior study author, Joel M. Gelfand, MD, MSCE, associate professor of Dermatology and Epidemiology. “The complications from diabetes and links to COPD, kidney disease and peptic ulcers we identified suggest new areas for research, while for the first time, demonstrating how increasing body surface area affected by psoriasis is directly associated with increasing risk of atherosclerotic disease.”

Although thought of as a disease limited to skin and joints, earlier work from the interdisciplinary Penn team has demonstrated the systemic effects of this chronic inflammatory disease; particularly those related to diabetes, cardiovascular disease and mortality. A higher risk of diabetes was previously identified in psoriasis patients, and this study revealed that additional diabetes-associated systemic complications, such as retinopathy and neuropathy, were correlated with the severity of psoriasis as well. The diseases share a common pathway — TH-1 cytokines — known to promote inflammation and insulin resistance. By identifying these co-occuring diseases, researchers hope patients will receive comprehensive care with proper health screening, evaluation and management.

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The above post is reprinted from materials provided by Perelman School of Medicine at the University of Pennsylvania. Note: Materials may be edited for content and length.

تاثير اندك توالي هاي ژني بر بروز پسوريازيس

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Coding variants in immune disease-related genes play only a small part in the overall genetic risk for psoriasis, according to a new study led by Anhui Medical University and BGI. This conclusion is strongly supported by their investigation on the contribution of functional coding variants to psoriasis in 21,309 Chinese individuals. In such a large-scale investigation, researchers only discovered two independent low-frequency variants with moderate effect on disease risk. The latest study was published online in Nature Genetics.

Psoriasis is a complex, chronic, lifelong skin disease. It typically first strikes people between the ages of 15 to 35, but can affect anyone at any age, including children. This terrible disease is the results of the interaction of multiple factors, such as environment, genetics, and immunology. The rapid and cost-effective sequencing technologies have enabled researchers to dig out numerous risk-associated variants in psoriasis, but the functional coding variants, particularly low-frequency and rare variants, have not been systematically investigated.

In this study, researchers took two-phase to identify coding variants. In the discovery stage, they conducted exome sequencing on 781 patients with psoriasis and 676 people without psoriasis as control. The efforts yielded 518,308 single-nucleotide variants (SNVs). Of these variants, 20.62% were nonsynonymous, and 68.13% were rare.

Considering the limitation of sample size and techniques in the discovery stage, researchers performed 2 independent studies in a large sample of 9,946 patients with psoriasis and 9,906 controls using targeted sequencing. A total of 3.2 Mb of coding DNA surrounding the targeted regions of 1,326 genes (covering 133 SNVs, 622 immune disease-related genes, and some top genes) was captured. They totally identified 82,387 nonsynonymous SNVs, of which 97.07% were rare.

Through further analysis, they discovered two independent missense SNVs in IL23R and GJB2 with low frequency and five common missense SNVs in LCE3D, ERAP1, CARD14 and ZNF816A associated with psoriasis at genome-wide significance. The rare missense SNVs in FUT2 and TARBP1 were also observed with suggestive evidence of association with this disease.

In addition to the SNVs analysis, researchers investigated 622 immune disease-related genes, and the results showed that the coding variants, at least common and low-frequency nonsynonymous variants, have limited independent contribution to psoriasis risk. Taking all the findings together, the study indicated that nonsynonymous SNVs in the 1,326 targeted genes had limited contribution to the overall genetic risk of psoriasis.

Compared with previous work on European population, this research also demonstrated the genetic heterogeneity between European and Chinese populations. The missense variant (rs72474224) in GJB2 seemed to be specific to Chinese individuals, while the one (rs11209026) in IL23R was specific to European individuals. And another common missense variant (rs11652075) in CARD14 showed consistent between European and Chinese samples.

Xin Jin, co-author of this study at BGI, said, “Target sequencing in such a large sample size enables us to investigate full spectrum of variants in these region. Although we did not identify any low-frequency or rare coding variants with strong genetic effect, the data helps us to refine several known GWAS loci and identify some candidate casual variants. It remains to be shown whether limited contribution of rare coding variants will also hold true for other regions outside the target and in other common diseases beyond psoriasis.”

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The above post is reprinted from materials provided by BGI Shenzhen. Note: Materials may be edited for content and length.

پسوريازيس با بيماري مزمن كليه ارتباط دارد

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Moderate to severe psoriasis is associated with an increased risk of chronic kidney disease (CKD) independent of traditional risk factors, such as diabetes and heart disease, finds a study published on bmj.com.

The authors recommend closer monitoring for kidney problems in patients with 3% or more of their body surface area affected to help detect and treat signs early and suggest careful consideration of medications which may cause kidney disease in this at risk patient population.

Psoriasis is a common, chronic inflammatory disease of the skin and joints that affects 2-4% of the general population. Increasing evidence suggests that psoriasis is associated with diabetes and heart disease independent of traditional risk factors. Some doctors think psoriasis may also be associated with kidney disease, but so far, studies have been small and shown conflicting results.

So a team of researchers based in Philadelphia, USA decided to compare the risk of chronic kidney disease in patients with and without psoriasis.

Using a UK primary care electronic medical records database (THIN), they identified 143,883 patients aged 18 to 90 years with psoriasis. These patients were matched with 689,702 patients without psoriasis who acted as controls. Patient with psoriasis who received phototherapy or oral or injectable (biologic) medications were defined as having severe disease.

The team then analysed how many of these patients had received a diagnosis of chronic kidney disease based on standard tests between 2003 and 2010.

Known risk factors for chronic kidney disease, such as age, sex, presence of diabetes, high blood pressure, high cholesterol levels, and use of NSAIDs were also taken into account.

The researchers found that patients with psoriasis, particularly those with severe disease, were at greater risk of developing moderate to advanced (stage 3 to 5) chronic kidney disease compared with control patients. Furthermore, those with severe psoriasis were nearly twice as likely to develop chronic kidney disease and were more than four times as likely to develop end stage renal disease requiring dialysis.

After adjusting for known risk factors, severe psoriasis remained an independent risk factor for chronic kidney disease and end stage renal disease requiring dialysis.

A further analysis of 8,731 psoriasis patients with measurements of affected body surface area matched to 87,310 patients without psoriasis showed similar results — a greater risk of chronic kidney disease in patients with moderate and severe disease.

Mild psoriasis is defined as limited disease with 2% or less body surface area affected, moderate as scattered disease with 3-10% body surface area affected and severe as extensive disease with more than 10% body surface area affected.

The combined results indicate that, although no association is seen in patients with truly mild disease, associations are seen in moderate and severe psoriasis, which are estimated to affect over 20% of patients worldwide, say the authors.

They also point out that, although the relative risk was higher in younger patients, the absolute risk of chronic kidney disease attributable to psoriasis increases with age.

For example, in patients aged 40-50 with severe disease, psoriasis accounts for one extra case of chronic kidney disease per 134 patients per year, and in those aged 50-60, it accounts for one additional case per 62 patients per year, they explain.

“Future studies are warranted to confirm our findings, determine the mechanisms mediating renal insufficiency in psoriasis, and examine the impact of treatment for psoriasis on the risk of chronic kidney disease,” they conclude.

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The above post is reprinted from materials provided by BMJ-British Medical Journal. Note: Materials may be edited for content and length.

درمان جديدبر اساس سيستم ايمتي براي پسوريازيس شناسائي شد

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Sanford-Burnham scientists have identified the B and T Lymphocyte Attenuator (BTLA) inhibitory receptor as a key factor in limiting inflammatory responses, particularly in the skin. The study, published online today in Immunity, provides clarity on how T cells get fired up to protect against pathogens, and then cool down to restore immune homeostasis.

“Our study shows that BTLA expression in gamma-delta T-cells deactivates their response to immune stimuli,” said Carl Ware, Ph.D., professor and director of the Infectious and Inflammatory Disease Center at Sanford-Burnham. “Gamma-delta T-cells are the first line of defense against pathogens — and unless ‘turned off’, can lead to unwanted inflammation and tissue destruction.”

Until now, scientists knew that gamma-delta T-cells were important for initiating inflammatory responses in the skin, but not how to turn off these potent cells.

“Now, we know that BTLA acts as a critical coordinator for turning T cells off to prevent the immune system from spinning out of control, and helping to rebalance the immune system,” said Ware.

The findings could help scientists develop new treatments for inflammatory disorders by targeting BTLA to reduce inflammation, promote homeostasis, and control disease.

How BTLA is regulated

Using a combination of human cells and a mouse model of psoriasis, the research team described a new pathway that regulates BTLA expression. Ware’s research showed that the “retinoid-related orphan receptor gamma-t” (ROR gamma-t) nuclear transcription factor works with interleukin (IL)-7, to coordinate the expression of BTLA, which in turn regulates gamma-delta T cell responses to inflammatory stimuli.

The study found that ROR gamma-t works to inhibit BTLA transcription, thereby limiting its availability in gamma-delta T-cells. This allows the expansion of T-cell numbers and their production of inflammatory cytokines, including IL-17 and TNF.

In contrast, IL-7 increases the availability of BTLA on the cell surface, reducing the number of active T cells and allowing BTLA to rein in the immune response.

“To be effective against pathogens, yet prevent damage from the body’s own defenses, the immune system has to maintain a balance. In essence, BTLA helps control inflammatory responses by reducing the activity and numbers of active gamma-delta T cells,” said Ware.

Immune mediated inflammatory diseases (IMIDs)

IMIDs are chronic, often disabling diseases caused by cytokine dysregulation and inflammation. There are over 80 types of IMIDs that target virtually any part of the body, including skin, connective tissue, and respiratory and gastrointestinal systems. Common IMIDs include Crohn’s disease, ulcerative colitis, psoriasis, rheumatoid arthritis and lupus. Approximately 5-7% of Western society suffers from an IMID that requires treatment.

Current treatments for IMIDs include corticosteroids, immuno-suppressants and “biologics” that target specific immune signaling molecules. While these therapies are very effective in some patients, many patients have a poor response to these drugs.

“Understanding the mechanisms that control immune responses creates important breakthroughs for researchers developing drugs to treat these chronic diseases. If a drug can selectively activate BTLA, we put the brakes on gamma-delta T-cells and gain control of inflammation, prevent damage, and if possible, achieve long-term disease remission,” said Ware.

استراتژي هاي جديد درمان پسوريازيس

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Almost ten years ago, the group led by Erwin Wagner, currently at the Spanish National Cancer Research Centre (CNIO), developed genetically modified mice showing symptoms very reminiscent to psoriasis. After publishing this discovery in Nature, the researchers decided to use this mouse model to study the underlying molecular pathways involved in disease development, and to look for innovative and efficient therapies. Now the group has discovered two possible novel treatments, based on existing pharmacological compounds, which are likely to cause fewer side effects.

Psoriasis affects up to 3% of the world’s population and can seriously affect the quality of life of these patients. The primary causes are largely unknown and the disease is not curable. The latest generation of drugs developed to combat it — so-called biological therapies — are thought to be a big step forward, but can only be applied for limited periods of time due to serious side effects, which can generate other forms of psoriasis, or even cause tuberculosis or leukemia. Due to this it is important for psoriatic patients to develop efficient non-toxic treatments.

The two new strategies now published by CNIO researchers are the result of in-depth studies of the disease biology that have revealed some of the underlying molecular causes.

In the first study published in the December issue of the high impact journal Immunity, it is shown how the symptoms of psoriasis disappear by deleting a protein called S100A9. In the second article, which is published in Science Translational Medicine, the researchers show that inhibiting a non-coding micro RNA, named miR-21, ameliorates the disease symptoms.

As Helia Schönthaler, the first author, and collegues write in Immunity: “over the past decade, biological therapies have been shown to be effective against inflammatory diseases. These treatments, however, are a cause of worry due to their side effects, which might cause a possible increase in the risk of infection or cancer. The development of efficient, locally applicable drugs without these side effects, therefore would be beneficial for patients with psoriasis.” Specifically, S100A9 inhibiting strategies “have the potential to become effective new treatments against psoriasis,” the authors state.

In the article in Science Translational Medicine, which features Juan Guinea-Viniegra as the lead author, the authors state that: “blocking miR-21 could offer advantages over current treatments given that the efficiency obtained is the same and the side effects are probably reduced.” The authors highlight that in the mouse model and in patient samples transplanted into mice this new strategy “shows a significant therapeutic response.”

Helia Schönthaler and Juan Guinea-Viniegra are members of the group of Erwin Wagner, who is the director of the F-BBVA-CNIO Cancer Cell Biology Programme.

IDENTIFYING THE IMPORTANT CHANGES

The different targets highlighted by the two studies reveal how complex and heterogeneous psoriasis is. A multitude of (epi-)genetic and environmental factors are involved, and until recently reliable animal models did not exist for modelling psoriasis. It is known that in each patient there might be dozens of different mutated or altered genes, and therefore it is not an easy task to bring order to such a web of alterations and to identify which ones can trigger and are causal to disease development.

One of the achievements of these studies is that the authors have done precisely that: they have identified some of the key alterations, as well as offering potential new targets on the relationship to previously discovered ones. In the mouse model reported by this group in 2005, for example, psoriasis symptoms appeared when two genes were eliminated from the mouse’s epidermis. Just two, but these two regulate the expression of many other genes.

Now Juan Guinea-Viniegra and Helia Schönthaler say not only that “there must be” a relationship between the two strategies they have proposed, but also with the altered genes from the 2005 study.

“Hundreds of increased or decreased genes have been described for psoriasis, but only a few of them — dozens — are supposed to be able to cause the disease,” they say. “We have described two new genes/proteins that are known to show increased levels in psoriasis, and have now shown that they play a causal role in the disease.”

Sophisticated molecular biology techniques have been used in both studies as well as using human samples. In the study led by Schönthaler, the first step was to compare skin affected by psoriasis patches with healthy skin from the same donor. To this end, and in collaboration with Esteban Daudén’s group at Madrid’s La Princesa Hospital, the group obtained samples from 19 patients with the most common type of psoriasis, and analysed the proteins found in the skin. The group identified 1217 proteins, of which 214 were present in significantly different amounts in healthy skin and psoriatic skin. Specifically, the protein complex S100A8-S100A9 was much more abundant in psoriasis.

Following this path the researchers studied the importance of S100A8-S100A9 and generated a mouse, prone to develop psoriasis symptoms, but in which this protein was missing. The result was that the symptoms of psoriasis in the psoriasis-like mouse model disappeared. The researchers also analysed the proteins that S100A8-S100A9 acts upon, finding other possible targets.

But the second piece of good news from this study is that it shows that a drug that is already on the market — presently used to treat prostate cancer blocks S100A9 and could be effective against psoriasis. “This does not mean that its use for psoriasis is going to be approved, but it makes the process easier, because it is a known drug we already know it is safe,” says Schönthaler.

MICE WITH HUMAN SKIN

The group led by Guinea-Viniegra explored another level of genome complexity coding for the information stored in DNA — microRNAs (miRNAs). miRNAs were discovered just two decades ago, and their role and function in complex diseases are not known in detail. miRNAs are small fragments of nucleic acid that are not translated into proteins, but can regulate the expression of other genes.

In the case of psoriasis, it was already known that the miR-21 was much more abundant in psoriatic skin than in healthy skin. To investigate its role, the researchers inhibited miR-21 first in the mouse model using compounds obtained from Santaris Pharma (Denmark), and saw how the symptoms disappeared in a short period of time with no apparent side effects.

The next step was to work with human samples. The authors grafted skin samples from a dozen patients onto live mice — a xeno-transplantation strategy (PDX-patient-derived xeno-transplants) that allows researchers to study the reaction of human tissue in vivo without treating the patient — and treated the lesions locally with the compound that blocks miR-21. “The results have been very positive and are encouraging, given that this would be a totally innovative way of treating psoriasis,” says Guinea-Viniegra.