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    Enteropathy-Associated T-Cell Lymphoma Type I Strongly Expresses CD30


    Jefferson Adams


    • A new understanding of CD30 expression in EATL could mean new treatments.


    Image Caption: Photo: CC--helices_colors--cc--The Wandering Angel.

    Celiac.com 10/25/2016 - Some potentially big news for people who suffer from enteropathy-associated T-cell lymphoma (EATL), an intestinal tumor that targets intraepithelial T lymphocytes. EATL may be preceded by refractory celiac disease (RCD), which resists treatment with gluten-free diet. In almost all cases, a range of the tumor cells express CD30.


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    RCD occurs in two types based on the absence (type I) or presence (type II) of abnormal intraepithelial lymphocytes (IEL) showing down-regulation of CD8 and often TCR gamma genes rearrangement. RCD II is now considered as a small cell intraepithelial T-cell lymphoma that could be an intermediate stage between celiac disease and EATL.

    A team of researchers recently set out to establish the pattern of CD30 expression in EATL, which help to improve therapies with the use of anti-CD30 monoclonal antibody like brentuximab vedotin (BV). The research team included David Sibon, Georgia Malamut, Virginie Verkarre, Coralie Derrieux, Isabelle Radford, Bertrand Meresse, Elizabeth Macintyre, Christophe Cellier, Nadine Cerf-Bensussan, Nicole Brousse, and Olivier Hermine.

    For their study, the team enrolled consecutive adult patients diagnosed with EATL between 2007 and 2013 in Necker University Hospital and Georges Pompidou European Hospital. The team confirmed celiac diagnosis using histopathologic and immunohistochemical review. For the purpose of the present study, two expert hematopathologists reviewed all EATL and extended the phenotypic analysis to reclassify them according to the 2008 WHO classification.

    The team used a panel of antibodies directed against CD20, CD3, CD4, CD5, CD8, CD56, granzyme B and ALK1. They also performed CD30 staining with Monoclonal Mouse Anti-Human CD30, Clone Ber-H2 (Dako). As a control group, they used consecutive RCDI and RCDII cases with complete phenotype and clonality analyses diagnosed in the same period. They based celiac disease diagnosis on HLA-DQ2/8 typing, detection of celiac specific antibodies, and of villous atrophy with increased counts of IEL on normal diet. They classified patients RCDI or II, depending on their clinical and histological response to a gluten-free diet, and the presence of abnormal IEL.

    In all 25 cases of EATL, large tumor cells strongly expressed CD30. In RCDI and II, CD30 was negative in most cases (∼90%), and was rarely expressed by dispersed atypical lymphocytes, whether in IEL or in lamina propria. TCR gamma genes were clonally rearranged in 11/14 (79%) EATL, 3/25 (12%) RCDI and 18/20 (90%) RCDII.

    Based on their findings, the team began a pilot study in 2012. The pilot study combines BV with chemotherapy followed by autologous stem-cell transplantation (ASCT) as frontline treatment for EATL. The team has treated five patients to date. For chemotherapy, the the first two patients received IVE/MTX. After presenting their initial results at ASH 2012 Annual Meeting, the team replaced IVE/MTX with CHP regimen, and treated 3 more patients. Both treatments were well tolerated, and all 5 patients reached clinical remission, and underwent ASCT.

    EATL type I strongly expresses CD30. Promising results from combining BV with CHP led the team to plan a phase 2 study of BV and CHP, followed by ASCT, as frontline treatment of EATL.

    Source:

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  • Related Articles

    Jefferson Adams
    Celiac.com 07/30/2012 - A number of studies have found higher rates of lymphoma in people with celiac disease. However, few studies make any distinction between lymphoproliferative disorders (LPDs).
    A team of researchers recently investigated rates of various lymphoproliferative disorders in patients with celiac disease.
    The research team included L.A. Leslie, B. Lebwohl, A.I. Neugut, J. Gregory Mears, G. Bhagat, and P.H. Green. They are affiliated with the Department of Medicine at Columbia University Medical Center in New York, NY.
    The team wanted to assess rates of LPD subtypes in celiac disease patients, describe patterns of celiac disease presentation in patients who develop LPD, and compare survival in patients with various LPD subtypes.
    To do so, they carried out a retrospective cohort study of adults with biopsy-proven celiac disease seen at a US referral center from 1981 to 2010. They also identified patients with comorbid LPD, and calculated standardized incidence ratios (SIR) for each LPD subtype.
    They began with a study group of 1,285 patients with celiac disease. The group contained 40 patients with LPD [sIR = 6.48, 95% confidence interval (CI) = 4.62-8.64] including 33 with non-Hodgkin lymphoma (NHL, SIR = 6.91, 95% CI = 4.26-8.28).
    Rates of NHL subtypes including enteropathy-associated T-cell (EATL, n = 12), non-EATL T-cell (SIR = 22.43, 95% CI = 7.08-46.41), diffuse large B-cell (SIR = 5.37, 95% CI = 1.93-10.52), mantle cell (SIR = 32.21, 95% CI = 6.07-78.97), and marginal zone (SIR = 37.17, 11.73-76.89), lymphoma were substantially higher
    among patients diagnosed with celiac before LPD (n = 24, NHL SIR = 4.47, 95% CI = 2.86-6.44).
    Patients who developed LPD were usually older at time of celiac diagnosis (57.9 ± 15.5 versus 42.5 ± 17.4 years, P < 0.0001) and more likely to present with diarrhea (60.0% versus 39.8% P = 0.016), abdominal pain (17.5% versus 5.5% P = 0.0046), and/or weight loss (12.5% versus 4.0%, P = 0.028).
    EATL patients had a shorter average survival than non-EATL NHL patients (3.2 versus 15.0 years, P = 0.016).
    Overall, rates of LPD are higher in celiac disease patients, and those diagnosed at an older age, who present with symptoms of malabsorption, are more likely to be diagnosed with LPD.
    Source:
    Am J Hematol. 2012 Apr 26. doi: 10.1002/ajh.23237.

    Jefferson Adams
    Celiac.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.
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    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.
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    Source:
    Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):306-9. doi: 10.1016/j.clml.2012.07.001.

    Jefferson Adams
    Celiac.com 04/15/2013 - Enteropathy-associated T cell lymphoma (EATL) is a gut cancer that often ends in death. Currently, doctors have very little idea what factors might help patients survive.
    The manner in which clinical presentation, pathological features and therapies influence EATL outcome was the subject of a recent study by a team of researchers.
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    They are variously affiliated with the Université Paris Descartes, the Gastroenterology Department of Hôpital Européen Georges Pompidou, APHP, and Inserm U989 in Paris, France.
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    Multivariate analysis showed that serum albumin level>21.6g/L, chemotherapy and reductive surgery were all significantly associated with increased survival rates (p
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    Source:
     Dig Liver Dis. 2013 Jan 9. pii: S1590-8658(12)00438-0. doi: 10.1016/j.dld.2012.12.001.

    Jefferson Adams
    Celiac.com 08/24/2015 - A new study reveals that U.S. Asians experience higher rates of deadlier cases of Enteropathy-associated T-cell lymphoma EATL.
    Enteropathy-associated T-cell lymphoma is a rare primary intestinal non-Hodgkin lymphoma (NHL) strongly associated with celiac disease. It is an aggressive disease with a median survival of approximately 10 months (Ferreri et al, 2011).
    Previous studies suggest that EATL may be more common in Europe and among Whites, among whom celiac disease is prevalent (Delabie et al, 2011; Ferreri et al, 2011). However, a second type of EATL (Type II) not associated with celiac disease is increasingly reported in Asia (Lee et al, 2005; Sun et al, 2011; Tan et al, 2013).
    To date, there have been no comparative epidemiological study in a racially diverse large population. A team of researchers recently set out to conduct such a study. The research team included Pawan K. Karanam, Mohammed Al-Hamadani, and Ronald S. Go. They are variously associated with the Departments of Medical Education and Medical Research at the Gundersen Medical Foundation in La Crosse, USA, and with the Division of Hematology at the Mayo Clinic, and the Mayo Clinic's Robert D, and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, MN, USA.
    The team turned to the two largest public cancer databases in the US: the Surveillance, Epidemiology, and End Results (SEER) database (http://www.seer.cancer.gov); and the National Cancer Data Base (NCDB; http://www.facs.org/quality-programs/cancer/ncdb).
    Using these databases, the research team was able to find and compare the cases of EATL by race. They were also able to describe the clinical features and overall survival (OS) for these cases. 
    The team's study included all patients with an EATL diagnosis according to International Classification of Diseases for Oncology (ICD-O: 9717). The team used SEER-18 registries from 2000 to 2011 to calculate incidence.
    To describe clinical outcomes, they used the NCDB NHL-PUF with patients diagnosed between 1998 and 2012 for clinical characteristics and those diagnosed between 1998 and 2006 for OS. Because CoC-accredited programs report survival data only once every 5 years, OS analysis was possible only for patients diagnosed between 1998 and 2006.
    From the data, the team calculated the incidence rate (case/1 000 000), age-adjusted to the 2000 standard US population, according to race (White, Black, Asian/Pacific Islander, American Indian/Alaska native) using seer*stat software version 8.1.5 (National Cancer Institute, Bethesda, MD, USA) and performed risk ratio comparisons using Poisson regression.
    They analyzed OS using the Kaplan–Meier method and used log-rank tests to compare survival distributions between race cohorts. The prognostic effect of pertinent clinical variables were studied using multivariate Cox proportional hazards models.
    They found that, for the years 2000–2010, the overall age-adjusted incidence rate of EATL in the US was 0·111 per 1,000,000. Asians/Pacific Islanders had a higher incidence rate (0·236) compared with other races [White (0·101), Black (0·107), American Indian/Alaska native (0·128)].
    The risk ratio of Asians/Pacific Islanders compared with non–Asians/Pacific Islanders was 2·32 [95% confidence interval (CI) 1·39–3·69; P = 0·002].
    The incidences for Asians and Pacific Islanders were combined in seer*stat, therefore we could not provide separate incidences for Asians and Pacific Islanders.
    All tests of statistical significance were two-sided and P < 0·05 was considered significant.
    Source:
    British Journal of Haematology, Vol. 170 Issue 3. DOI: 10.1111/bjh.13555

  • Recent Articles

    Jefferson Adams
    Celiac.com 06/19/2018 - Could baking soda help reduce the inflammation and damage caused by autoimmune diseases like rheumatoid arthritis, and celiac disease? Scientists at the Medical College of Georgia at Augusta University say that a daily dose of baking soda may in fact help reduce inflammation and damage caused by autoimmune diseases like rheumatoid arthritis, and celiac disease.
    Those scientists recently gathered some of the first evidence to show that cheap, over-the-counter antacids can prompt the spleen to promote an anti-inflammatory environment that could be helpful in combating inflammatory disease.
    A type of cell called mesothelial cells line our body cavities, like the digestive tract. They have little fingers, called microvilli, that sense the environment, and warn the organs they cover that there is an invader and an immune response is needed.
    The team’s data shows that when rats or healthy people drink a solution of baking soda, the stomach makes more acid, which causes mesothelial cells on the outside of the spleen to tell the spleen to go easy on the immune response.  "It's most likely a hamburger not a bacterial infection," is basically the message, says Dr. Paul O'Connor, renal physiologist in the MCG Department of Physiology at Augusta University and the study's corresponding author.
    That message, which is transmitted with help from a chemical messenger called acetylcholine, seems to encourage the gut to shift against inflammation, say the scientists.
    In patients who drank water with baking soda for two weeks, immune cells called macrophages, shifted from primarily those that promote inflammation, called M1, to those that reduce it, called M2. "The shift from inflammatory to an anti-inflammatory profile is happening everywhere," O'Connor says. "We saw it in the kidneys, we saw it in the spleen, now we see it in the peripheral blood."
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    The research was funded by the National Institutes of Health.
    Read more at: Sciencedaily.com

    Jefferson Adams
    Celiac.com 06/18/2018 - Celiac disease has been mainly associated with Caucasian populations in Northern Europe, and their descendants in other countries, but new scientific evidence is beginning to challenge that view. Still, the exact global prevalence of celiac disease remains unknown.  To get better data on that issue, a team of researchers recently conducted a comprehensive review and meta-analysis to get a reasonably accurate estimate the global prevalence of celiac disease. 
    The research team included P Singh, A Arora, TA Strand, DA Leffler, C Catassi, PH Green, CP Kelly, V Ahuja, and GK Makharia. They are variously affiliated with the Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Lady Hardinge Medical College, New Delhi, India; Innlandet Hospital Trust, Lillehammer, Norway; Centre for International Health, University of Bergen, Bergen, Norway; Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Gastroenterology Research and Development, Takeda Pharmaceuticals Inc, Cambridge, MA; Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy; Department of Medicine, Columbia University Medical Center, New York, New York; USA Celiac Disease Center, Columbia University Medical Center, New York, New York; and the Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
    For their review, the team searched Medline, PubMed, and EMBASE for the keywords ‘celiac disease,’ ‘celiac,’ ‘tissue transglutaminase antibody,’ ‘anti-endomysium antibody,’ ‘endomysial antibody,’ and ‘prevalence’ for studies published from January 1991 through March 2016. 
    The team cross-referenced each article with the words ‘Asia,’ ‘Europe,’ ‘Africa,’ ‘South America,’ ‘North America,’ and ‘Australia.’ They defined celiac diagnosis based on European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines. The team used 96 articles of 3,843 articles in their final analysis.
    Overall global prevalence of celiac disease was 1.4% in 275,818 individuals, based on positive blood tests for anti-tissue transglutaminase and/or anti-endomysial antibodies. The pooled global prevalence of biopsy-confirmed celiac disease was 0.7% in 138,792 individuals. That means that numerous people with celiac disease potentially remain undiagnosed.
    Rates of celiac disease were 0.4% in South America, 0.5% in Africa and North America, 0.6% in Asia, and 0.8% in Europe and Oceania; the prevalence was 0.6% in female vs 0.4% males. Celiac disease was significantly more common in children than adults.
    This systematic review and meta-analysis showed celiac disease to be reported worldwide. Blood test data shows celiac disease rate of 1.4%, while biopsy data shows 0.7%. The prevalence of celiac disease varies with sex, age, and location. 
    This review demonstrates a need for more comprehensive population-based studies of celiac disease in numerous countries.  The 1.4% rate indicates that there are 91.2 million people worldwide with celiac disease, and 3.9 million are in the U.S.A.
    Source:
    Clin Gastroenterol Hepatol. 2018 Jun;16(6):823-836.e2. doi: 10.1016/j.cgh.2017.06.037.

    Jefferson Adams
    Celiac.com 06/16/2018 - Summer is the time for chips and salsa. This fresh salsa recipe relies on cabbage, yes, cabbage, as a secret ingredient. The cabbage brings a delicious flavor and helps the salsa hold together nicely for scooping with your favorite chips. The result is a fresh, tasty salsa that goes great with guacamole.
    Ingredients:
    3 cups ripe fresh tomatoes, diced 1 cup shredded green cabbage ½ cup diced yellow onion ¼ cup chopped fresh cilantro 1 jalapeno, seeded 1 Serrano pepper, seeded 2 tablespoons lemon juice 2 tablespoons red wine vinegar 2 garlic cloves, minced salt to taste black pepper, to taste Directions:
    Purée all ingredients together in a blender.
    Cover and refrigerate for at least 1 hour. 
    Adjust seasoning with salt and pepper, as desired. 
    Serve is a bowl with tortilla chips and guacamole.

    Dr. Ron Hoggan, Ed.D.
    Celiac.com 06/15/2018 - There seems to be widespread agreement in the published medical research reports that stuttering is driven by abnormalities in the brain. Sometimes these are the result of brain injuries resulting from a stroke. Other types of brain injuries can also result in stuttering. Patients with Parkinson’s disease who were treated with stimulation of the subthalamic nucleus, an area of the brain that regulates some motor functions, experienced a return or worsening of stuttering that improved when the stimulation was turned off (1). Similarly, stroke has also been reported in association with acquired stuttering (2). While there are some reports of psychological mechanisms underlying stuttering, a majority of reports seem to favor altered brain morphology and/or function as the root of stuttering (3). Reports of structural differences between the brain hemispheres that are absent in those who do not stutter are also common (4). About 5% of children stutter, beginning sometime around age 3, during the phase of speech acquisition. However, about 75% of these cases resolve without intervention, before reaching their teens (5). Some cases of aphasia, a loss of speech production or understanding, have been reported in association with damage or changes to one or more of the language centers of the brain (6). Stuttering may sometimes arise from changes or damage to these same language centers (7). Thus, many stutterers have abnormalities in the same regions of the brain similar to those seen in aphasia.
    So how, you may ask, is all this related to gluten? As a starting point, one report from the medical literature identifies a patient who developed aphasia after admission for severe diarrhea. By the time celiac disease was diagnosed, he had completely lost his faculty of speech. However, his speech and normal bowel function gradually returned after beginning a gluten free diet (8). This finding was so controversial at the time of publication (1988) that the authors chose to remain anonymous. Nonetheless, it is a valuable clue that suggests gluten as a factor in compromised speech production. At about the same time (late 1980’s) reports of connections between untreated celiac disease and seizures/epilepsy were emerging in the medical literature (9).
    With the advent of the Internet a whole new field of anecdotal information was emerging, connecting a variety of neurological symptoms to celiac disease. While many medical practitioners and researchers were casting aspersions on these assertions, a select few chose to explore such claims using scientific research designs and methods. While connections between stuttering and gluten consumption seem to have been overlooked by the medical research community, there is a rich literature on the Internet that cries out for more structured investigation of this connection. Conversely, perhaps a publication bias of the peer review process excludes work that explores this connection.
    Whatever the reason that stuttering has not been reported in the medical literature in association with gluten ingestion, a number of personal disclosures and comments suggesting a connection between gluten and stuttering can be found on the Internet. Abid Hussain, in an article about food allergy and stuttering said: “The most common food allergy prevalent in stutterers is that of gluten which has been found to aggravate the stutter” (10). Similarly, Craig Forsythe posted an article that includes five cases of self-reporting individuals who believe that their stuttering is or was connected to gluten, one of whom also experiences stuttering from foods containing yeast (11). The same site contains one report of a stutterer who has had no relief despite following a gluten free diet for 20 years (11). Another stutterer, Jay88, reports the complete disappearance of her/his stammer on a gluten free diet (12). Doubtless there are many more such anecdotes to be found on the Internet* but we have to question them, exercising more skepticism than we might when reading similar claims in a peer reviewed scientific or medical journal.
    There are many reports in such journals connecting brain and neurological ailments with gluten, so it is not much of a stretch, on that basis alone, to suspect that stuttering may be a symptom of the gluten syndrome. Rodney Ford has even characterized celiac disease as an ailment that may begin through gluten-induced neurological damage (13) and Marios Hadjivassiliou and his group of neurologists and neurological investigators have devoted considerable time and effort to research that reveals gluten as an important factor in a majority of neurological diseases of unknown origin (14) which, as I have pointed out previously, includes most neurological ailments.
    My own experience with stuttering is limited. I stuttered as a child when I became nervous, upset, or self-conscious. Although I have been gluten free for many years, I haven’t noticed any impact on my inclination to stutter when upset. I don’t know if they are related, but I have also had challenges with speaking when distressed and I have noticed a substantial improvement in this area since removing gluten from my diet. Nonetheless, I have long wondered if there is a connection between gluten consumption and stuttering. Having done the research for this article, I would now encourage stutterers to try a gluten free diet for six months to see if it will reduce or eliminate their stutter. Meanwhile, I hope that some investigator out there will research this matter, publish her findings, and start the ball rolling toward getting some definitive answers to this question.
    Sources:
    1. Toft M, Dietrichs E. Aggravated stuttering following subthalamic deep brain stimulation in Parkinson’s disease--two cases. BMC Neurol. 2011 Apr 8;11:44.
    2. Tani T, Sakai Y. Stuttering after right cerebellar infarction: a case study. J Fluency Disord. 2010 Jun;35(2):141-5. Epub 2010 Mar 15.
    3. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    4. Jäncke L, Hänggi J, Steinmetz H. Morphological brain differences between adult stutterers and non-stutterers. BMC Neurol. 2004 Dec 10;4(1):23.
    5. Kell CA, Neumann K, von Kriegstein K, Posenenske C, von Gudenberg AW, Euler H, Giraud AL. How the brain repairs stuttering. Brain. 2009 Oct;132(Pt 10):2747-60. Epub 2009 Aug 26.
    6. Galantucci S, Tartaglia MC, Wilson SM, Henry ML, Filippi M, Agosta F, Dronkers NF, Henry RG, Ogar JM, Miller BL, Gorno-Tempini ML. White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain. 2011 Jun 11.
    7. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    8. [No authors listed] Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1988. A 52-year-old man with persistent watery diarrhea and aphasia. N Engl J Med. 1988 Oct 27;319(17):1139-48
    9. Molteni N, Bardella MT, Baldassarri AR, Bianchi PA. Celiac disease associated with epilepsy and intracranial calcifications: report of two patients. Am J Gastroenterol. 1988 Sep;83(9):992-4.
    10. http://ezinearticles.com/?Food-Allergy-and-Stuttering-Link&id=1235725 
    11. http://www.craig.copperleife.com/health/stuttering_allergies.htm 
    12. https://www.celiac.com/forums/topic/73362-any-help-is-appreciated/
    13. Ford RP. The gluten syndrome: a neurological disease. Med Hypotheses. 2009 Sep;73(3):438-40. Epub 2009 Apr 29.
    14. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71.

    Jefferson Adams
    Celiac.com 06/14/2018 - Refractory celiac disease type II (RCDII) is a rare complication of celiac disease that has high death rates. To diagnose RCDII, doctors identify a clonal population of phenotypically aberrant intraepithelial lymphocytes (IELs). 
    However, researchers really don’t have much data regarding the frequency and significance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. Such data could provide useful comparison information for patients with RCDII, among other things.
    To that end, a research team recently set out to try to get some information about the frequency and importance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. The research team included Shafinaz Hussein, Tatyana Gindin, Stephen M Lagana, Carolina Arguelles-Grande, Suneeta Krishnareddy, Bachir Alobeid, Suzanne K Lewis, Mahesh M Mansukhani, Peter H R Green, and Govind Bhagat.
    They are variously affiliated with the Department of Pathology and Cell Biology, and the Department of Medicine at the Celiac Disease Center, New York Presbyterian Hospital/Columbia University Medical Center, New York, USA. Their team analyzed results of TCR-GR analyses performed on SB biopsies at our institution over a 3-year period, which were obtained from eight active celiac disease, 172 celiac disease on gluten-free diet, 33 RCDI, and three RCDII patients and 14 patients without celiac disease. 
    Clonal TCR-GRs are not infrequent in cases lacking features of RCDII, while PCPs are frequent in all disease phases. TCR-GR results should be assessed in conjunction with immunophenotypic, histological and clinical findings for appropriate diagnosis and classification of RCD.
    The team divided the TCR-GR patterns into clonal, polyclonal and prominent clonal peaks (PCPs), and correlated these patterns with clinical and pathological features. In all, they detected clonal TCR-GR products in biopsies from 67% of patients with RCDII, 17% of patients with RCDI and 6% of patients with gluten-free diet. They found PCPs in all disease phases, but saw no significant difference in the TCR-GR patterns between the non-RCDII disease categories (p=0.39). 
    They also noted a higher frequency of surface CD3(−) IELs in cases with clonal TCR-GR, but the PCP pattern showed no associations with any clinical or pathological feature. 
    Repeat biopsy showed that the clonal or PCP pattern persisted for up to 2 years with no evidence of RCDII. The study indicates that better understanding of clonal T cell receptor gene rearrangements may help researchers improve refractory celiac diagnosis. 
    Source:
    Journal of Clinical Pathologyhttp://dx.doi.org/10.1136/jclinpath-2018-205023