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Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.com 07/08/2013 - Right now, the only way for doctors to distinguish between the complicated and uncomplicated forms of celiac disease is to use invasive methods. In an effort to find a way other than these invasive methods to distinguish between uncomplicated and complicated forms of celiac disease, a research team set out to study serum parameters in the spectrum of celiac disease The research team included Greetje J Tack, Roy LJ van Wanrooij, B Mary E Von Blomberg, Hedayat Amini, Veerle MH Coupe, Petra Bonnet, Chris JJ Mulder, and Marco WJ Schreurs. They are variously affiliated with the Departments of Epidemiology and Biostatistics, Gastroenterology and Hepatology, and Pathology of VU University Medical Centre in Amsterdam, The Netherlands, and with the Department of Immunology, Erasmus MC at theUniversity Medical Centre in Rotterdam, The Netherlands. The team's cohort study looked at the possible use of new testing methods, including IL-6, IL-8, IL-17, IL-22, sCD25, sCD27, granzyme-B, sMICA and sCTLA-4 in patients diagnosed with active celiac disease, celiac disease following a gluten-free diet, Refractory celiac disease (RCD) types I and II, and enteropathy associated T-cell lymphoma (EATL). The results showed elevated levels of the pro-inflammatory IL-8, IL-17 and sCD25 in both active celiac disease and RCDI-II. In addition, patients with RCDII showed higher serum levels of soluble granzyme-B and IL-6 compared with active celiac disease patients. They did not find any differences between RCDI and active celiac disease, or between RCDI and RCDII. However, they did find that EATL patients had higher IL-6 levels compared with all other groups. This study document a specific series of serum parameters that show that RCDII and EATL have distinct immunological features compared with uncomplicated celiac disease and RCDI. This new method of distinguishing uncomplicated and complicated forms of celiac disease might promote the development of non-invasive procedures in the future. Source: BMC Gastroenterology 2012, 12:159. doi:10.1186/1471-230X-12-159.
Jefferson Adams posted an article in Cancer, Lymphoma and Celiac DiseaseCeliac.com 11/08/2012 - T-cell lymphoma is a deadly type of cancer that is more common in people with celiac disease than in the general population. Currently, there is no cure for T-cell lymphoma, and no promising treatment exists for people who suffer from this condition. However, that may be set to change, as the results of a new study suggest that new treatments for T-cell lymphoma my be on the horizon. The study appears in the journal Clinical Lymphoma Myeloma and Leukemia. The study team included J.R. Bertino, M. Lubin, N. Johnson-Farley, W.C. Chan, L. Goodell, and S. Bhagavathi. They are affiliated with the Departments of Medicine, Pharmacology, and Pathology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ. The team was attempting to address the fact that doctors treating T-cell lymphomas, especially types of T-cell lymphoma known as peripheral T-cell lymphoma (PTCL), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL) have limited treatment options and cannot cure the condition. Their study noted that a high percentage of PTCL, AITL, and ALCL, along with T-cell leukemia and T-cell lymphoblastic leukemia lack the enzyme methylthioadenosine phosphorylase (MTAP). Their published results also note that MTAP-deficient cells cannot cleave endogenous methylthioadenosine to adenine and 5-methylthioribose-1-phosphate, a precursor of methionine, and as a result have enhanced sensitivity to inhibitors of de novo purine biosynthesis. A recently introduced antifolate, pralatrexate, which has been shown to inhibit de novo purine biosynthesis, has been approved for treatment of PTCL and may have an increasing role in therapy. An alternative strategy involving coadministration of methylthioadenosine and high-dose 6-thioguanine has been proposed and may prove to be selectively toxic to MTAP-deficient uncommon lymphomas. As a result of these MTAP results, the team suggests that new therapies and treatments for T-cell lymphoma may be possible going forward. Source: Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):306-9. doi: 10.1016/j.clml.2012.07.001.
Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchPatients Diagnosed in Childhood Might Evolve toward Latency on a Normal Diet Celiac.com 05/23/2007 - The results of a study recently published in the journal Gut indicate that some people who suffer from celiac disease might not need to remain on a gluten free diet for their entire lives, and that some celiac patients might be able to safely introduce gluten containing foods without suffering a relapse. Previous Studies Showing Positive Response to Wheat Introduction in Patients with Celiac Disease are Promising, But Incomplete Several studies have shown that some patients diagnosed with celiac disease in childhood were able to remain on a gluten-containing diet after gluten challenge without suffering a relapse. However, most of these studies included a small number of patients, or followed the patients for only a short period after gluten was reintroduced into their diets. These previous studies also limited their evaluation largely to assessment of celiac disease serology and histology of duodenal biopsies, and did not attempt to identify what factors might predict the development of tolerance to gluten. Determining Long-term Response to Gluten Consumption in Celiac Disease Patients A research team made up of doctors Tamara Matysiak-Budnik (1), Georgia Malamut (1,2), Natacha Patey-Mariaud de Serre (3), Etienne Grosdidier (2), Sylvie Seguier (3), Nicole Brousse (3), Sophie Caillat-Zucman (4), Nadine Cerf-bensussan (1), Jacques Schmitz (5) and Christophe Cellier (1,2), set out to determine whether children diagnosed with celiac disease must follow a gluten free diet for life. To determine the effects of reintroducing gluten into the diets of celiac patients, the research team set out to monitor the clinical and physical progress of adult celiac patients who had been diagnosed as children, who underwent a gluten challenge, and who were asymptomatic. The study focused on a specific group of patients, all but two of whom were diagnosed as children and followed until adulthood in the Department of Pediatric Gastroenterology in Necker Hospital and thereafter at the Georges Pompidou European Hospital in Paris; after which, they were entered into a local register of adult celiac patients and were recruited for the study based on two criteria: celiac disease diagnosed in childhood; and adherence to a normal diet. The patients in the study were from 18 to 65 years old, and had been diagnosed with celiac disease in childhood. The research team recorded data in the following categories: biological parameters of malabsorption; bone mineral density; clinical celiac status; gluten intake; HLA genotype; serological markers of celiac disease; as well as histological and immuno-histochemical parameters in duodenal biopsies. Results Show 20% Long-term Latency in Celiac Patients who Eat Normal Diet Of those studied, 61 patients had returned to a normal diet, and were asymptomatic. 48 showed various degrees of villous atrophy (silent celiac disease), and 13 had no detectable atrophy (latent celiac disease) on duodenal biopsies. Compared to those with silent celiac disease, patients with latent celiac disease showed markedly less osteopenia/osteoporosis [1/9 (11%) versus 23/33 (70%), p<0.001)], and lower TcR- + intraepithelial T cell counts (38±20 vs. 55±15, p<0.01). Patients with latent celiac disease had a lower mean age at the time of their first gluten free diet compared to patients with silent celiac disease (14.4±5 vs 40.1±47 months, p<0.05). Compared to the seven control patients on a long-term gluten free diet, the latent patients did not differ significantly, except for a higher frequency of celiac disease-specific serum antibodies. However, a follow-up found that two of the patients with latent celiac disease had suffered a clinical and histological relapse. Results showed that of those patients who remained asymptomatic after the reintroduction of gluten, 20% showed long-term latency. The study concludes that some patients with celiac disease may not need to remain on a life-long gluten free diet, and that some may indeed be able to safely reintroduce gluten into their diets with no adverse effects. However, the latency patients may experience may be transient, and therefore a regular follow-up is necessary. Also, patients with silent celiac disease should remain on a gluten free diet. Participating hospitals: (1) INSERM, U793, Faculté de Médecine René Descartes, IFR94, Paris, France. (2) AP-HP, H&OCIRC;pital Européen Georges Pompidou, Department of Hepato-Gastroenterology, Paris, France. (3) AP-HP, H&OCIRC;pital Necker-Enfants Malades, Department of Pathology, Paris, France. (4) INSERM, Equipe Avenir, Faculté de Médecine René Descartes, Paris, France. (5) AP-HP, H&OCIRC;pital Necker-Enfants Malades, Department of Pediatric Gastroenterology, Paris, France. Gut 2006;13(10). Comments on this Study by Ron Hoggan This is dressed up like a new finding, but it isn't. There are a number of studies that show similar findings. Part of that problem lies in the interpretation of the biopsies, and part of the problem arises out of failing to recognize the variable nature of the disease. It has long been known to wax and wane for reasons beyond our ken. Samuel Gee (1888) and Gibbons (1889) both reported the cyclic nature of their patients symptoms. They cited a study to support the idea of a two year rule saying that relapse would usually occur within two years, yet Kuitunen P, Savilahti E, Verkasalo M., in Late mucosal relapse in a boy with coeliac disease and cows milk allergy. Acta Paediatr Scand. 1986 Mar;75(2):340-2. reported one patient who at 4.3 years on a normal diet showed normal villous architecture. It was not until a follow-up biopsy at more than 8 years of eating a gluten-containing diet that he showed villous atrophy. These findings, along with all the other studies that have shown long delays in some patients before relapsing, argue strongly for Michael N. Marsh's position that we should concentrate on treating any immune system that is sensitized to gluten with a gluten-free diet. His rectal challenge is an excellent tool for identifying such sensitized immune systems. Dr. Fines fecal antibody test probably fits into the same category. The underlying assumption is that the biopsy will identify all cases of intestinal lesion regardless of the possibility of patchy lesions that are well documented in the literature. They deal with increased IEL counts as if they were a feature of latent celiac disease when that is not the case. There are several other points on which this study falters. They admit that the latency can be transient. Unfortunately, they have not exchanged emails with people where they have returned to eating gluten and have developed an abdominal cancer. I exchanged emails with such a young man who blamed himself for having killed himself with his carelessness about his diet. How awful that was for him! Yet these authors seem to think it is quite acceptable for patients to indulge during their latency periods and only consider a diet if there is a relapse of intestinal lesion.