The study was conducted a team that included Joe West, MD, an epidemiologist and honorary consultant gastroenterologist at the University of Nottingham.

The study found that people with celiac disease who are unvaccinated against pneumococcus are about 30% more likely to develop community-acquired pneumonia (CAP) than are unvaccinated people without celiac disease.

Dr. West says the increased risk is likely due to weakened spleen function in people with celiac disease.

This elevated risk was not seen in vaccinated celiac patients, or people over 65 years of age.

The results of the study suggest that clinicians be extra vigilant about vaccinating celiac patients, and health officials in the United Kingdom are now recommend that people with celiac disease receive pneumococcus vaccinations.

Source:

• Open Original Shared Link 

Celiac.com 09/09/2015 - Some researchers and clinicians suspect a connection between eosinophilic esophagitis (EoE) and celiac disease, but prior studies have shown conflicting results

A team of researchers recently set out to determine the relationship between EoE and celiac disease among patients with concomitant esophageal and duodenal biopsies. The research team included Elizabeth T. Jensena, Swathi Eluria, Benjamin Lebwohl, Robert M. Gentab, and Evan S. Dellon.

For their cross-sectional study, they team used data covering the period from January 2009 through June 2012 from a U.S. national pathology database.

They defined esophageal eosinophilia as the presence of ≥15 eosinophils per high-power field. The crude and age and sex adjusted odds of esophageal eosinophilia for patients with active celiac disease were compared with those without celiac disease.

Sensitivity analyses were performed by using more stringent case definitions and by estimating the associations between celiac disease and reflux esophagitis and celiac disease and Barrett’s esophagus.

Out of 292,621 patients in the source population, the team looked at data from 88,517 patients with both esophageal and duodenal biopsies. Four thousand one hundred one (4.6%) met criteria for EoE, and 1203 (1.4%) met criteria for celiac disease. Patients with celiac disease had 26% higher odds of EoE than patients without celiac disease (adjusted odds ratio, 1.26; 95% confidence interval [CI], 0.98–1.60).

The strength of the connection varied according to EoE case definition, but all definitions showed a weak positive association between the two conditions.

Interestingly, this study showed no connection between celiac disease and reflux esophagitis (adjusted odds ratio 0.95; 95% CI, 0.85–1.07) or between celiac disease and Barrett’s esophagus (adjusted odds ratio 0.89; 95% CI, 0.69–1.14).

Overall, this study showed only a weak increase in EoE in patients with celiac disease. The connection strengthened in direct relation to the strength of definitions of EoE, and was not seen with other esophageal conditions.

Doctors should consider concomitant EoE in patients with celiac disease where clinical indications support it.

Disclosures: Dellon reports receiving research funds from Meritage Pharma, consulting for Aptalis, Novartis, Receptos and Regeneron, and receiving an educational grant from Diagnovus.

Source:

• Open Original Shared Link

Celiac.com 08/19/2015 - For the first time since it was described and named by 1st century Greek physician Aretaeus of Cappadocia, first linked to wheat in the 1940's, and specifically linked to gluten in 1952, scientists have discovered the cause of celiac disease.

Professor Ludvig Sollid, and his team at the Centre for Immune Regulation at University of Oslo, have discovered that people with celiac disease suffer from one of two defective human leukocyte antigens (HLAs), which cause the immune system to see gluten molecules as dangerous, triggering the immune response that causes classic celiac-associated inflammation and other symptoms.

To be true, the team was not working in the dark. They were armed with a complete map of the genes, an understanding that two types of HLA (HLA-DQ2 and HLA-DQ8) predispose a person for celiac disease, and the very crucial recent discovery by a team of German colleagues that celiac patients have antibodies for a very precise enzyme: transglutaminase 2.

"We also found that the bits of gluten that were presented to the T-cells have some changes caused by an enzyme in the body – transglutaminase 2", says Sollid. HLAs are proteins which act as markers, binding to fragments of other proteins, and telling T-cells how to treat them.

So it wasn't much of a stretch for Professor Sollid's team to determine that the defective HLAs bind to fragments of gluten, causing the T-cells to treat them as bacteria or viruses.

Basically, two HLA types present gluten remnants to the T-cells, causing the T-cells to regard the gluten as dangerous, and to trigger immune reactions that cause inflammation in the intestines, and this is what causes celiac disease.

"We think that this is huge," Sollid said. "We understand the immune cells that are activated and why they are activated."

At present, Professor Sollid and his group are investigating how antibodies against transglutaminase are formed.

This is a simple, but huge moment in the annals of medicine and in the annals of celiac disease. It's a discovery that will help researchers develop new approaches to treatment, and/or a cure for celiac disease in the future.

Source:

• Open Original Shared Link

Celiac disease is a T-cell-mediated immune disorder in which gliadin-derived peptides activate lamina propria effector CD4+ T cells.

This activation triggers the release of cytokines, compatible with a Th1-like pattern, which play a crucial role in the development of celiac disease, and which control many aspects of the inflammatory immune response.

Previous studies revealed that a novel subset of effector T cells, marked by expression of high levels of IL-17A, termed Th17 cells, plays a key role in celiac disease.

Although these effector T cell subsets produce pro-inflammatory cytokines, which cause significant tissue damage in celiac sufferers, recent studies have suggested the existence of additional CD4(+) T cell subsets with suppressor functions.

These subsets include type 1 regulatory T cells and CD25(+)CD4(+) regulatory T cells, expressing the master transcription factor Foxp3, which have important implications for the development and progression of celiac disease.

Source:

• Open Original Shared Link

Celiac.com 08/10/2015 - The presence of specific human leukocyte antigen-DQ2 and DQ8 seems to be necessary for celiac disease development, but its usefulness for screening is still uncertain.

A research team recently set out to conduct a systematic review and meta-analysis of the diagnostic performance of human leukocyte antigen typing tests for celiac disease screening. The research team included A. Díaz-Redondo, J. Miranda-Bautista, J. García-Lledó, J.P. Gisbert, and L. Menchén. They are variously affiliated with the Hospital General Universitario Gregorio Marañón in Madrid, Spain, and with the Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Madrid, Spain.

The team conducted a systematic review of published studies assessing accuracy of human leukocyte antigen DQ2 and DQ8 typing for the detection of celiac disease. They searched MEDLINE and EMBASE for the period running from 1st January 2004 until 31st December 2013 and used two independent researchers to carry out selection and classification of studies, data extraction and analysis.

The team conducted meta-analysis that combined sensitivities, specificities and likelihood ratios of HLA-DQ2 and DQ8 for the diagnosis of celiac disease and ended up with six studies that included a total of 1303 people. The results showed pooled sensitivity at 98%, with 95% confidence interval: 97-99. Overall specificity was 45% (95% confidence interval: 41-48).

Regarding specificity, studies were heterogeneous and a the team ran a subgroup analysis according to the type of population included. Overall negative likelihood ratio was 0.05 (0.03-0.09).

Because it offers high sensitivity and low negative likelihood ratio, the team concludes that human leukocyte antigen-DQ2/DQ8 typing makes an appropriate test for ruling out celiac disease in the general population suffering related symptoms, and even more in at risk population.

Source:

• Open Original Shared Link

A research team recently set out to assess the risk of non-celiac autoimmune disease in first-degree relatives and spouses of people with celiac disease.

The research team included Louise Emilsson, Cisca Wijmenga, Joseph A. Murray, and Jonas F. Ludvigsson. They are variously affiliated with the Primary Care Research Unit, Vårdcentralen Värmlands Nysäter, Värmland County, Sweden, the Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Oslo, Norway, the Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, and with the Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.

The team found individuals with celiac disease by searching computerized duodenal and jejunal biopsies, collected from 1969 through 2008, at 28 pathology departments in Sweden.

The team found 29,096 patients with celiac disease based on biopsy reports of villous atrophy of Marsh grade 3 or higher and matched individuals with celiac disease with up to 5 of 144,522 non-celiac control patients based on sex, age, county, and calendar year.

Through Swedish health care registries, the team identified all first-degree relatives (fathers, mothers, siblings, and offspring) and spouses of 84,648 individuals with celiac disease, and 430,942 control subjects. The team used Cox regression analysis to calculate hazard ratios (HRs) for non-celiac autoimmune disease, such as Crohn’s disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, or ulcerative colitis, within these groups.

Cox analysis showed that during the follow-up period averaging just under 11 years, nearly 3333, or 4%, of the first-degree relatives of patients with celiac disease, and 12,860 relatives of controls (3.0%), had an autoimmune disease other than celiac disease.

First-degree relatives of people with celiac disease had an increased risk of non-celiac autoimmune disease, compared with controls (HR, 1.28; 95% confidence interval, 1.23–1.33), as did spouses (HR, 1.20; 95% confidence interval, 1.06–1.35).

Risk estimates for non-celiac autoimmune disease did not differ between first-degree relatives and spouses of individuals with celiac disease (interaction test: P = .11). Hazard Ratios for non-celiac autoimmune disease were highest in the first 2 years of follow-up evaluation.

First-degree relatives and spouses of individuals with celiac disease have a significantly higher risk of non-celiac autoimmune disease.

In addition to genetic factors, environmental factors and better awareness, testing and diagnosis might influence rates of autoimmune disorders in first-degree relatives of individuals with celiac disease.

Source:

•  Open Original Shared Link

Celiac.com 07/07/2015 - Could proprietary antigen-specific nano-particles offer a potential cure for celiac disease? Early results are very positive, say a team of researchers.

In what will likely prove to be interesting news for many people with celiac disease, Cour Pharmaceutical Development Company has announced "a significant breakthrough in celiac treatment [that] has the potential to cure celiac patients rather than relying on gluten avoidance, immune suppressive regimens or dietary supplements," according to a company press release.

According to the release, new data from a pre-clinical live animal study demonstrate a reversal of the effects of dietary gluten exposure in animals sensitized to gluten.

If true, their use of robust antigen specific nano-particle therapy could be a major breakthrough in celiac disease treatment.

A study conducted at the Haartman Institute of the University of Helsinki tested Cour's novel bio-engineered nano-particles, COUR-NP-GLI, in an animal model of celiac disease. The COUR-NP-GLI are Toleragenic Immune Modifying nanoParticles (TIMP) consisting of a safe proprietary polymer and antigenic proteins (gliadins). The antigens are fully encapsulated for safety and dosing is administered intravenously.

Once processed, the TIMPs control and regulate the auto-reactive T-cells, the primary driver of disease.

Cour's targeted antigen-specific therapy has been successfully studied across multiple disease models including multiple sclerosis, type 1 diabetes, food allergies and now celiac disease. COUR-NP-GLI works by targeting a broad set of gliadin proteins found in wheat gluten, the class of antigenic proteins widely regarded as the main cause of celiac disease. Treatment with COUR-NP-GLI ameliorated symptoms of celiac disease even during gluten consumption.

The study team concludes that Cour-NP-GLI was safely administered via intravenous infusion, while
Cour-NP-GLI treated animals previously sensitized to gluten maintained normal body weight even during continued exposure to gluten containing diet.

Animals treated with Cour-NP-GLI showed significantly better duodenal biopsies results compared to non-treated animals. Cour-NP-GLI treated animals showed significantly lower inflammatory cytokines compared to non-treated animals. Overall, animals treated with Cour-NP-GLI showed comparable or better results than animals treated with a gluten-free diet.

The company presented data on Cour-NP-GLI at the 16th Annual International Celiac Disease Symposium, held June 21-24, 2015 in Prague, Czech Republic.

While there have been other claims made about potential cures, this is the first animal model demonstration of a treatment that effectively cures celiac disease. If these results hold up to scrutiny, and if successful treatments can be developed, this approach has tremendous potential to benefit numerous people with celiac disease.

Now, to be fair, much study, review, and consideration must happen for such a treatment to be developed, but it is exciting news, nonetheless.

Source:

• Open Original Shared Link

Although a number of studies have documented this reduced response, most have been limited by low numbers of patients with celiac disease, and/or lower numbers of control patients, said Maria José Pérez, MD, from Henares Hospital in Coslada, Spain.

Two of those prior studies that implicated gluten in the impaired vaccine response, showed that celiac patients who follow a gluten-free diet have a hepatitis B vaccine response that is similar to that in the general population after celiac patients switch to a gluten-free diet.

In their study, Dr. Pérez and her colleagues looked at the immune response to the vaccine in children with celiac disease. The team evaluated 214 children with celiac disease and 346 control patients who had completed the hepatitis B vaccine regimen in the first year of life. All patients were vaccinated before gluten was introduced into their diets. They measured gluten antibody levels for each child to determine vaccine response. Kids who showed levels of hepatitis B surface antibody under 10 mUI/mL were defined as non-responsive to the vaccine.

Overall, non-response was 8% higher in children with celiac disease than in control subjects (68.7% vs 60.7%). For children younger than 5 years, this difference was a whopping 20%, with a rate of 50.0% for celiac children, compared with 30.1% for the control group (P = .015).

In children with celiac disease, the researchers found no relation between level of antibody and time since the last intake of gluten. So, one important takeaway is that gluten consumption or avoidance does not change the immune response to hepatitis B vaccine in patients with celiac disease. Over time, levels of antibody decreased in both groups, so doctors assessing immune response to hepatitis B vaccine should factor in the amount of time elapsed since vaccination, says Dr. Pérez.

The prospective study involved 72 children with celiac disease who were vaccinated in the first year of life and whose antibody levels were below 10 mUI/mL. The researchers found no change in levels after the children received a single vaccine booster.

In light of these results, the research team advises that children with celiac disease and undetectable levels of antibody be revaccinated with a full series of the vaccine.

Source:

• Open Original Shared Link

In fact, the adoption of gluten-free diets by non-celiac athletes has risen sharply in recent years due to perceived ergogenic and health benefits. New research however, casts doubt on those ideas.

The research was conducted by a team that set out to evaluate the effects of a gluten-free diet (GFD) on exercise performance, gastrointestinal (GI) symptoms, perceived well-being, intestinal damage, and inflammatory responses in non-celiac athletes. The research team included Dana Lis, Trent Stellingwerff, Cecilia M. Kitic, Kiran D.K., and James Fell.

For their study, they looked at thirteen competitive endurance cyclists, 8 male, 5 female, with no positive clinical screening for celiac disease or history of irritable bowel syndrome.

These cyclists followed a seven day gluten-containing diet (GCD) or GFD separated by a 10-day washout in a controlled randomized double-blind, cross-over study. Cyclists ate a GFD alongside either gluten-containing or gluten-free food bars, while the team controlled habitual training and nutrition behaviors. Total gluten intake was 16g wheat gluten per day.

During each diet, cyclists completed the Daily Analysis of Life Demand for Athletes (DALDA) and GI questionnaires, both before and after exercise and daily.

On day seven cyclists completed a sub-maximal steady-state (SS) 45 minute ride at 70% peak power followed by a 15 minute time-trial (TT).

The researchers took blood samples before exercise, post SS and post TT to determine intestinal fatty acid binding protein (IFABP) and inflammatory markers (cytokine responses: IL-1[beta], IL-6, IL-8, IL-10, IL-15, TNF-[alpha]). They employed mixed effect logistic regression to analyze data.

The results showed that TT performance was basically the same (p=0.37) between the GCD (245.4+/-53.4kJ) and GFD (245.0+/-54.6kJ).

GI symptoms during exercise, daily, and DALDA responses were also similar for each diet (p>0.11). There were no significant differences in IFABP (p=0.69) or cytokine (P>0.13) responses.

These results show that a short-term GFD has no impact on performance, GI symptoms, well-being, or upon a select indicator of intestinal injury or inflammatory markers in non-celiac endurance athletes.

So, basically, if you're an athlete who does not have celiac disease, then a gluten-free diet is not going to provide any performance or recovery benefits to you.

Source:

• Open Original Shared Link

Celiac.com 06/22/2015 - Currently available digestive enzymes do not fully degrade gluten, and are thus of questionable use for people with celiac disease or gluten intolerance, say a team of researchers. Prior research had shown that post-proline cutting enzyme effectively degrade the immunogenic gluten peptides. Several existing digestive enzyme supplements claim to promote gluten degradation.

The research team set out to assess the degradation of immunogenic gluten epitopes by currently available digestive enzymes. The team included G. Janssen, C. Christis, Y. Kooy-Winkelaar, L. Edens, D. Smith, P. van Veelen, and F. Koning. They are variously affiliated with the Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands, DSM Food Specialties in Delft, The Netherlands, and DSM Food Specialties in South Bend, Indiana, USA.

For their study, they assessed five commercially available digestive enzyme supplements along with purified digestive enzymes. They assessed these enzymes using enzyme assays and mass spectrometric identification. They monitored gluten epitope degradation using R5 ELISA, mass spectrometric analysis of the degradation products, and T cell proliferation assays. 

They found that the enzyme supplements leave the nine immunogenic epitopes of the 26-mer and 33-mer gliadin fragments largely intact. This is due to the high proline content of gluten molecules, which prevents gastrointestinal proteases from fully degrading them, leaving large proline-rich gluten fragments intact, including an immunogenic 33-mer from α-gliadin and a 26-mer from γ-gliadin.

These latter peptides can trigger pro-inflammatory T cell responses resulting in tissue remodeling, malnutrition and a variety of other complications.

In contrast, the pure enzyme AN-PEP effectively degraded all nine epitopes in the pH range of the stomach at much lower dose.

From these results, the team concludes that most of the currently available digestive enzyme supplements are ineffective in degrading immunogenic gluten epitopes, but the AN-PEP do effectively degrade gliadin fragments.

Source:

• Open Original Shared Link

Many alternative health practitioners recommend gluten-free diets for people who claim to be sensitive to gluten, but do not have celiac disease. Despite numerous reports of people without celiac disease experiencing celiac-like symptoms when eating gluten, there are currently no clear diagnostic guidelines for NCGS. NCGS is still diagnosed by excluding celiac disease, and finding no reliable celiac biomarkers.

A team of researchers recently set out to evaluate the prevalence, diagnostic exclusion of celiac disease and the efficacy of a gluten-free diet (GFD) for NCGS patients.

The research team included J. Molina-Infante; S. Santolaria; D. S. Sanders; and F. Fernández-Bañares. They are variously affiliated with the Department of Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain, the Department of Gastroenterology, Hospital San Jorge, Huesca, Spain, the Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK, the Department of Gastroenterology, Hospital Universitario Mutua Terrassa, Barcelona, Spain, and with CIBERehd, Barcelona, Spain.

Their team conducted a PubMed search through December 2014. They defined NCGS as self-reported gluten intolerance, negative celiac serology and absence of villous atrophy. They also included studies evaluating the impact of a GFD on patients with irritable bowel syndrome (IBS).

They found that rates of NCGS (0.5–13%) varied considerably. Seventeen studies met the inclusion criteria for NCGS. The studies included 1561 patients, 26 of whom were children. HLA haplotypes could not be linked to histology, either by normal or lymphocytic enteritis (LE)] in 1,123 NCGS patients. Nearly half (44%) of NCGS patients tested positive for HLADQ2/DQ8 haplotypes.

Using advanced diagnostic techniques that combine LE and HLADQ2/DQ8 haplotypes, the team reclassified 39 (20%) of 189 NCGS cases as celiac disease.

They found a higher than expected family history of celiac disease and autoimmune disorders in NCGS patients. For HLADQ2 positive diarrhea-predominant IBS patients, a GFD resulted in variable, but significantly improved stool frequency.

Rates of NCGS are extremely variable. A subset of NCGS patients might actually be part of what many researchers refer to as celiac disease "light."

The long term benefit of a gluten-free diet for NCGS patients is currently unclear, but certainly the diet, if well-balanced, would not cause any issues. The researchers do note that HLADQ2 positive diarrhea-type IBS patients might gain symptom improvement from a gluten-free diet.

Clearly more studies are needed to determine if NCGS is a bona fide medical condition, as many suspect. Until then, there is very little treatment available from medical practitioners, and many people with self-diagnosed NCGS will doubtless be left to self-treatment. For many, this will include avoiding gluten.

Do you, a loved one, or someone you know have gluten-sensitivity without celiac disease? Share your thoughts and comments below.

Source:

•  Open Original Shared Link

A team of researchers recently set out to fine map the MHC association signal to identify additional celiac disease risk factors independent of the HLA-DQA1 and HLA-DQB1 alleles. The researchers included J. Gutierrez-Achury, A. Zhernakova, S.L. Pulit, G. Trynka, K.A. Hunt, J. Romanos, S. Raychaudhuri, D.A. van Heel, C. Wijmenga, and P.I. de Bakker.

Their team fine mapped the MHC association signal looking for risk factors other than the HLA-DQA1 and HLA-DQB1 alleles, and the found five new associations that account for 18% of the genetic risk.

Taking these new loci together with the 57 known non-MHC loci, genetic variation can now explain up to 48% of celiac disease heritability.

Nailing down exactly what genetic factors influence the heritability of celiac disease will help researchers to better understand the disease, and to develop better treatments and screening options.

Research team members are variously affiliated with the Department of Genetics, University Medical Center, University of Groningen, Groningen, the Netherlands, the Department of Medical Genetics at the Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands, the Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK, the Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA, the Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA, the Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, the Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester, UK, the Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands, and with the Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.

Source:

• Open Original Shared Link