Abstract
The 14th International Celiac Disease Symposium (ICDS) took place in Oslo, Norway, on 20–22 June 2011, with 530 registered attendees, including clinicians, researchers, sponsors and patients. The 3-day symposium included an international scientific section, and a concurrent clinical forum. It provided a comprehensive overview of the basic, clinical and translational aspects of celiac disease in two keynote lectures, 11 introductory presentations, ten lectures from experts, 227 poster presentations and 38 oral presentations. It highlighted the importance of integrating the knowledge from clinics, genetic studies and immunological studies to better understand celiac disease.
Opening ceremony
The 14th International Celiac Disease Symposium was held in Oslo, Norway, on 20–22 June 2011. There were 530 participants, including clinicians, researchers, sponsors and patients. In his opening address, Knut Peterson, Managing Director of the Norwegian Celiac Society, pointed out that long-term projects in celiac disease (CD) research are vital. Frode Vartdal, Dean of the Medical Faculty at the University of Oslo (Oslo, Norway) welcomed all the participants to Oslo and to the 14th International Celiac Disease Symposium; this was followed by a wonderful performance by the Norwegian singer Silvia Moi.
Genetics, diagnosis & epidemiology of CD
The first day included three sessions and a keynote lecture. The first scientific session was on genetics. The introduction to this session, entitled ‘Celiac disease genetics: the knowns and unknowns’, was presented by Ross McManus (Trinity College Dublin, Ireland), who summarized the contribution of genetic studies towards identifying HLA and non-HLA susceptibility loci for CD.
The role of genome-wide association studies in identifying 39 non-HLA susceptibility loci was described by Cisca Wijmenga (University Medical Center Groningen, The Netherlands). She also reported an example of a meta-analysis of genome-wide association studies results in CD and rheumatoid arthritis and highlighted the possibilities of finding more shared risk alleles by performing cross-disease meta-analysis in autoimmune diseases. The keynote lecture on: ‘Genetics of complex inflammatory diseases: crystal gazing in the era of whole genome sequencing’ was presented by David van Heel (Blizard Institute of Cell and Molecular Science, London, UK). He presented the results from different technical strategies such as Immunochip, exome sequencing and whole-genome sequencing to pinpoint the causative variants in confirmed susceptibility loci and/or to identify new associations to CD. He discussed the advantages and disadvantages of each approach and concluded that the Immunochip approach had been very successful in identifying 13 new loci for CD as well as localizing the causative variants in 29 loci to much smaller linkage disequilibrium blocks (to single genes), whereas exome sequencing and whole-genome sequencing strategies may require a very large number of cases and controls to satisfy the statistical power needed to detect new CD loci.
The second session was on diagnosis. In an introductory lecture, Riccardo Troncone (University Federico II, Naples, Italy) suggested that CD is not just a gluten-sensitive enteropathy and that it is necessary to standardize the diagnostic criteria to clearly classify the different phenotypes of gluten sensitivity, including CD. This can be done by combining genetics, specific auto-antibody profiles and histological observations, along with the various symptoms. However, CD symptoms are so diverse, this may prove challenging.
Katri Kaukinen (University of Tampere and Tampere University Hospital, Finland) presented the role of serological tests in diagnosing CD as an alternative to biopsy in her lecture entitled: ‘Celiac disease diagnostics beyond conventional histology’. She concluded that the sensitivity and specificity of serological tests are improving compared with using histology alone and that the possibility of making an early diagnosis of CD without biopsy should be considered, particularly in endomysial antibody-positive subjects since they will benefit from a gluten-free diet (GFD) irrespective of their small bowel mucosal morphology and symptoms. However, a diagnosis based solely on serology may suffer from the genetic heterogeneity among individuals and variability in technique (quality of antibodies). Steffen Husby (Odense University Hospital, Denmark) gave a lecture on: ‘New ESPGHAN criteria for diagnosis of CD’. He discussed the results of a questionnaire among the members of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), in which approximately 90% of the members requested a modification of the 1990 criteria that are currently used. He concluded that since we now have much better serological and genetic tests to diagnose CD, biopsies should be omitted whenever possible (anti-tissue transglutaminase (TG2) >ten-times normal levels, endomysial antibody-positive and HLA-DQ2/DQ8-positive).
The third session of the day was on epidemiology. Peter Green (Columbia University, NY, USA) described how the clinical presentation of CD, with common, nongastrointestinal presentations, is highly variable both in children and adults. The molecular mechanism of generation of such variable symptoms is still not clear. Anneli Ivarsson (Umeå University, Sweden) discussed the three strategies of CD prevention. Primary prevention by the early introduction of gluten and its impact will be studied using the PreventCD cohort and the Empirical Therapy of Idiopathic Chronic Singultus (ETICS) study. Secondary prevention is effected by actively asking about CD-related symptoms in the clinic, which could lead to 38% of hidden cases being found. Tertiary prevention is via an improved GFD with increased social support to CD patients.
Immunology, pathogenesis & animal models
The fourth session focused on the immunological aspects of CD. In his introductory lecture, Frits Koning (Leiden University Medical Center, The Netherlands) proposed a model to explain why T-cell clones from children are not reactive to known peptides. He suggested that, in CD, we may have epitope spreading followed by epitope focusing, and we thus see the initial process in children and the end process in adults.
Ludvig Sollid (Oslo University Hospital, Norway) gave a lecture entitled: ‘The autoantibody response to transglutaminase 2 in CD’. He showed that TG2-specific IgA plasma cells are highly abundant only in the intestine of active CD patients and they preferentially recognize the open conformation of the TG2 enzyme. He also presented evidence to show that only IgD acts as a substrate for TG2 enzyme. He proposed a model in which TG2-mediated cross-linking of anti-TG2 IgD, but not IgA, may lead to recruitment of the TG2-specific plasma cells. He suggested that B cells may be heavily involved in presenting gluten to T-cell receptors and, in turn, amplification of the antigluten T-cell response.
Adrian Hayday (London Research Institute, UK) presented a keynote lecture on immunology entitled: ‘Regulation of gut T cells by regulator of G-protein signaling 1 (RGS-1) illustrating precise opportunities and grand challenges for human immunology’. In a T-cell transfer model of colitis, he demonstrated that T cells lacking RGS-1 were unable to induce severe colitis, suggesting a role for RGS-1 in promoting gut inflammatory pathology. He also discussed the possibility of targeting RGS-1 as a valid clinical target because of its specificity. However, there are still several unanswered questions, such as why it has such a high expression in the gut and what impact it has on the infection process.
Shuo-Wang Qiao (University of Oslo, Norway) and Elena Verdu (McMaster University, ON, Canada) chaired the fifth session of the day on animal models. Bana Jabri (University of Chicago, IL, USA) discussed what we have learnt from mouse models in understanding CD pathology and pointed out that mouse models are still needed to understand the role of TG2 in CD pathogenesis and the mechanism behind generation of anti-TG2 antibodies. Janneke Samsom (Erasmus Medical Center, Rotterdam, The Netherlands) presented a lecture entitled: ‘Early events of primary T-cell differentiation after gliadin feed’. Feeding of deamidated gliadin to double-transgenic mice that express HLA-DQ2 and a gliadin-specific humanized T-cell receptor resulted in the development of tolerance in which an IL-10-producing gliadin-specific T-cell response, but not Foxp3+ T-cells, was seen in the spleen. Thus, future studies are necessary to understand whether there are any specific defects in the generation of such suppressive gliadin-specific T cells in CD which could inhibit gliadin-specific effector T-cell proliferation.
Clinical presentation, follow-up & imaging
The eighth session was chaired by Geoffrey Holmes (University of Nottingham, UK) and Chris Mulder (VU University Medical Center, The Netherlands). Lundin discussed the challenges faced by clinicians. He stressed that it is a difficult clinical task to diagnose CD accurately, since similar symptoms are presented by other diseases. Thus, the biopsy standard needs to be improved and we should consider high-definition endoscopy for imaging. Daniel Leffler (Beth Israel Deaconess Medical Center, MA, USA) then discussed his experiences of monitoring CD patients. In the USA, CD patients may not be completely gluten free for psychological reasons, because of the cost of the GFD, or because of hidden gluten contamination, among other reasons. He concluded that there is a need for well-trained CD diagnosticians as the serology alone is not effective. There is significant variability in management guidelines used in the USA and the efficiency of disease management, while the cost–effectiveness should be a priority for clinical research.
Malignancy
Inger Nina Farstad (Rikshospitalet University Hospital, Oslo, Norway) and Harald Vogelsang (Medical University of Vienna, Austria) chaired the ninth session on malignancy. Jonas Ludvigsson (Karolinska University Hospital, Stockholm, Sweden) gave an overview showing that CD patients have a 55% increased cancer risk (three out of 1000 CD patients) compared with controls (two out of 1000 controls) in the introductory lecture.
Type II refractory CD (RCDII) is a condition where villous atrophy persists even after 6 months of strict GFD with massive accumulation of abnormal intraepithelial lymphocytes and eventually results in enteropathy-associated T-cell lymphoma. Nadine Cerf-Bensussan (INSERM, Paris, France) demonstrated that increased expression of IL-15 in the gut epithelium of RCDII patients prevents the apoptosis of RCD intraepithelial lymphocytes by activating the Jak3/STAT5 signaling pathway and antiapoptotic factor Bcl-2. Later, she concluded that blocking IL-15 could be an effective therapeutic strategy.
Overall, the 14th International Celiac Disease Symposium was a great success. Thanks to the Norwegian Celiac Society, the symposium provided a well-organized, excellent platform for discussions on the advances in basic, clinical and translational research in CD. The 15th International Celiac Disease symposium is scheduled to take place on 22–25 September 2013 in Chicago (IL, USA) Citation[1].
Acknowledgement
The authors thank Jackie Senior for her assistance in editing this manuscript.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Website
- 15th International Celiac Disease Symposium www.icds2013.org