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02/07/2018 - Babesiosis is a malaria-like parasitic disease caused by infection with Babesia, a genus of Apicomplexa, which is commonly spread via the bite of infected Ixodes ticks, by blood transfusion or congenitally. Although most patients with babesiosis typically have a fever, there can also be non-specific symptoms, which can triggers delays or errors in diagnosis. Babesia divergens is considered the main agent of human babesiosis in Europe. A team of researchers recently reported a case of a celiac disease patient with splenic dysfunction from resulting in severe babesiosis. Their report describes a 79-year-old Irish man with hyposplenism and splenic atrophy due to adult celiac disease, who became critically ill from a severe Babesia divergens infection. So far, this is particular report about a single patient doesn't give much information beyond citing the development itself, and urging doctors to be on the lookout for possible consequences of splenic dysfunction from adult celiac disease, such as serious pneumococcal infections and babesiosis. The report does mirror, or touch on, another clinical report from Spain in 2016. In that report, by Arsuaga, et. al., a 35-year old patient with normal splenic function presented with persistent nonspecific symptoms such as the recurrence of fever, chills, headaches, weakness, general malaise, and constant fatigue over several months. As fever indicated an infectious disease, laboratory tests were carried out for a large number of pathogens, including Anaplasma phagocytophilum, B. divergens, and B. microti. After initial treatment with atovaquone/proguanil and azithromycin failed to produce results, the patient remained on that drug regimen for 10 weeks without side effects. Although the patient still had frequent episodes of fever, his general condition improved. At the end of the treatment, the bouts of fever were resolved and the patient's only symptom was fatigue. In follow-up visits during the subsequent 4 months, PCR analysis revealed that the patient had cleared the parasites. Though these reports have been isolated, they do indicate that doctors should watch for possible consequences of splenic dysfunction from adult celiac disease, such as serious pneumococcal infections and babesiosis. Celiac.com will follow and report on any developments in this story. Sources: Ticks Tick Borne Dis. 2017 Jun;8(4):537-539. doi: 10.1016/j.ttbdis.2017.02.016. Epub 2017 Feb 28. Vector-Borne and Zoonotic Diseases. October 2016, 16(10): 677-679. The clinical team included S O'Connell, C Lyons, M Abdou, R Patowary, S Aslam, N Kinsella, A Zintl, KP Hunfeld, GP Wormser, J Gray, C Merry, and H Alizadeh. They are variously affiliated with the Department of Infectious Diseases, St. James's Hospital, Dublin, Ireland, the Department of Surgery, Letterkenny University Hospital, Letterkenny, Ireland, the Department of Haematology, Letterkenny University Hospital, Letterkenny, Ireland, the Department of Haematology, St. James's Hospital, Dublin, Ireland, the School of Veterinary Medicine, University College Dublin, Dublin, Ireland, the Institute for Laboratory Medicine, Microbiology & Infection Control, Northwest Medical Centre, Academic Teaching Hospital, Goethe-University, Frankfurt, Germany, the Division of Infectious Diseases, Department of Medicine, New York Medical College, Valhalla, NY, USA, the UCD School of Biology and Environmental Science, University College Dublin, Dublin 4, Ireland, the Department of Infectious Diseases, St. James's Hospital, Dublin 8, Ireland; Northwestern Memorial University Chicago, USA; Makerere University Uganda, Uganda, the Department of Haematology, Letterkenny University Hospital, Letterkenny, Ireland; and with Pecs University, Faculty of General Medicine, Pecs, Hungary.
Celiac.com 06/21/2017 - Circulating gluten-specific FOXP3+CD39+ regulatory T cells have impaired suppressive function in patients with celiac disease. What does that mean? Although researchers understand the effector T-cell response in patients with celiac disease pretty well, they really don't know very much about the role played by regulatory T cells (Treg cells) in the loss of tolerance to gluten. To get a better picture, a team of researchers recently set out to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3)+ Treg cells. The research team included L Cook, CML Munier, N3 Seddiki, D van Bockel, N Ontiveros, MY Hardy, JK Gillies, MK Levings, HH Reid, J Petersen, J Rossjohn, RP Anderson, JJ Zaunders, JA Tye-Din, AD Kelleher. For the study, gluten-free patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. The research team collected peripheral blood before and after challenge. To effectively measure the gluten-specific CD4+ T-cell response, they combined traditional IFN-γ ELISpot with a test for antigen-specific CD4+ T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation, but relies instead on antigen-induced co-expression of CD25 and OX40 (CD134). During the gluten challenge, levels of circulating gluten-specific Treg cells and effector T cells both rose sharply, peaking on the sixth day. The team recounts surprise on discovering that about 80% of the ex vivo circulating gluten-specific CD4+ T cells were FOXP3+CD39+Treg cells, which reside within the pool of memory CD4+CD25+CD127lowCD45RO+ Treg cells. Even though they saw normal suppressive function in peripheral polyclonal Treg cells from celiac patients, after a short in vitro expansion, the gluten-specific FOXP3+CD39+ Treg cells showed sharply reduced suppressive function compared with polyclonal Treg cells. The team's study offers the first estimates of FOXP3+CD39+ Treg cell frequency within circulating gluten-specific CD4+ T cells after oral gluten challenge of celiac patients. FOXP3+CD39+ Treg cells made up the majority of all circulating gluten-specific CD4+ T cells, but they showed reduced suppressive function, indicating that Treg cell dysfunction might be a key factor in celiac disease development. This type of research is crucial to help document the genetic physiology of celiac disease, which will help researchers to better understand and treat the disease itself. Source: J Allergy Clin Immunol. 2017 Mar 8. pii: S0091-6749(17)30343-3. doi: 10.1016/j.jaci.2017.02.015. The researchers are variously affiliated with the Immunovirology and Pathogenesis Program, The Kirby Institute, UNSW Sydney, Sydney, Australia, St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, Australia; the Infection and Immunity Program, The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Australia; the Immunovirology and Pathogenesis Program, The Kirby Institute, UNSW Sydney, Sydney, Australia; St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, Australia, Immunology Division, Walter and Eliza Hall Institute, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia; Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; the Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom; the Immunology Division, Walter and Eliza Hall Institute, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia; ImmusanT, Cambridge, Massachusetts; and the Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Australia.
Celiac.com 12/08/2008 - Celiac disease is a life-long autoimmune enteropathy that results in damage to the small intestinal mucosa. When people with celiac disease eat the gluten proteins found in wheat, rye and barley, they damage the cells that line the small intestine, which interferes with normal digestion and absorption of nutrients. Recent studies have shown that most people present with a silent, non-diarrheal form of the disease, and show no obvious symptoms. People with celiac disease face rates of autoimmune disease that are10 times higher than the general population. People with untreated celiac disease have higher rates of thyroid problems, which generally improve with the adoption of a gluten-free diet. A connection between the span of gluten consumption and autoimmune diseases has been observed in people with celiac disease. Tissue transglutaminase (TGase) is a ubiquitous enzyme and manifests in all tissues, with both intra- and extracellular localization. A team of researchers recently set out determine if tissue transglutaminase-2 IgA antibodies (anti-TGase II) present in blood samples from celiac disease patients react with thyroid tissue and possibly contribute to thyroid disease. The research team made up of doctors Afzal J. Naiyer, Jayesh Shah, Lincoln Hernandez, Soo-Youl Kim, Edward J. Ciaccio, Jianfeng Cheng, Sanil Manavalan, Govind Bhagat, and Peter H.R.Green. The team took blood samples from 40 people with active celiac disease, but not following a gluten free diet, samples from 46 celiac patients on a gluten-free diet (celiac disease), 40 normal controls (NC), and 25 with Crohn’s disease. They screened all samples for anti-thyroperoxidase antibodies (TPO-AB) and thyroglobulin antibodies (TG-AB), and conducted indirect immunofluorescence on primate thyroid tissue sections using TPO-AB– and TG-AB–negative blood samples. The team performed indirect immunofluorescence on thyroid seronegative, anti-TGase II–positive celiac disease+ blood samples (n1/423) and observed staining patterns on thyroid follicular cells and extracellular matrices that was identical with monoclonal anti-human TGase II antibody. Signs of TGase II as the antigen in thyroid tissue were reinforced by elimination of the IIF pattern when sera were depleted of anti-TGase II by pretreatment with human recombinant TGase II. The team saw no such staining of thyroid tissue in blood samples from celiac disease patients who were negative for TGase II antibodies, or samples from the non-celiac control group. Thyroid antibodies were found in 43% of celiac disease+ patients, substantially higher than NC and CROHN patients ( p < 0.0001). Moreover, a positive correlation was observed between anti-TGase II and TPO-AB titers (p1/40.0001; r1/40.63). The results show that anti-TGase II antibodies bind to TGase II in thyroid follicles and extracellular matrix, and that titers correlate with TPO antibody titers. This indicates that anti-TGase II antibodies might contribute to the development of thyroid disease in people with celiac disease. Thyroid Volume 18, Number 11, 2008