To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Prevalence of inflammatory bowel disease among coeliac disease patients in a Hungarian coeliac centre

BACKGROUND: Celiac disease, Crohn disease and ulcerative colitis are inflammatory disorders of the gastrointestinal tract with some common genetic, immunological and environmental factors involved in their pathogenesis. Several research shown that patients with celiac disease have increased risk of developing inflammatory bowel disease when compared with that of the general population. The aim of this study is to determine the prevalence of inflammatory bowel disease in our celiac patient cohort over a 15-year-long study period. METHODS: To diagnose celiac disease, serological tests were used, and duodenal biopsy samples were taken to determine the degree of mucosal injury. To set up the diagnosis of inflammatory bowel disease, clinical parameters, imaging techniques, colonoscopy histology were applied. DEXA for measuring bone mineral density was performed on every patient. RESULTS: In our material, 8/245 (3,2 %) coeliac disease patients presented inflammatory bowel disease (four males, mean age 37, range 22-67), 6/8 Crohn's disease, and 2/8 ulcerative colitis. In 7/8 patients the diagnosis of coeliac disease was made first and inflammatory bowel disease was identified during follow-up. The average time period during the set-up of the two diagnosis was 10,7 years. Coeliac disease serology was positive in all cases. The distribution of histology results according to Marsh classification: 1/8 M1, 2/8 M2, 3/8 M3a, 2/8 M3b. The distribution according to the Montreal classification: 4/6 Crohn's disease patients are B1, 2/6 Crohn's disease patients are B2, 2/2 ulcerative colitis patients are S2. Normal bone mineral density was detected in 2/8 case, osteopenia in 4/8 and osteoporosis in 2/8 patients. CONCLUSIONS: Within our cohort of patients with coeliac disease, inflammatory bowel disease was significantly more common (3,2 %) than in the general population

Beneficial use of immunoglobulins in the treatment of Sydenham chorea

This double case report indicates that treatment with intravenous immunoglobulins (IVIG) is effective in patients with Sydenham chorea (SC). SC is a rare but impressive clinical manifestation following streptococcal infection. This movement disorder characterised by chorea, emotional lability and muscle weakness, is one of the major criteria of acute rheumatic fever. Treatment of SC is typically limited to supportive care and palliative medications. Curative treatment is still in the experimental stage. Recent research on patients with SC proved that antibodies against the group A streptococcus cross-react with epitopes of neurons in the basal ganglia, namely, intracellular tubulin and extracellular lysoganglioside. Therefore, immune modulating therapy by means of prednisone, plasma exchange and IVIG are mentioned in the literature as possible effective treatment. Beneficial effect of IVIG has been shown in several diseases with molecular mimicry as the underlying pathophysiology. In this paper, we describe two girls aged 11 and 13 years, respectively, who presented with SC having severe disabilities in their daily live. We treated both patients with IVIG 400 mg/kg/day for 5 days. Treatment was tolerated well and had a pronounced positive effect. Shortly after the drug was administered, all signs and symptoms disappeared in both patients. Based upon these patients, we highlight IVIG as a serious treatment option for SC

Climate change, phenological shifts, eco-evolutionary responses and population viability: toward a unifying predictive approach

The debate on emission targets of greenhouse gasses designed to limit global climate change has to take into account the ecological consequences. One of the clearest ecological consequences is shifts in phenology. Linking these shifts to changes in population viability under various greenhouse gasses emission scenarios requires a unifying framework. We propose a box-in-a-box modeling approach that couples population models to phenological change. This approach unifies population modeling with both ecological responses to climate change as well as evolutionary processes. We advocate a mechanistic embedded correlative approach, where the link from genes to population is established using a periodic matrix population model. This periodic model has several major advantages: (1) it can include complex seasonal behaviors allowing an easy link with phenological shifts; (2) it provides the structure of the population at each phase, including the distribution of genotypes and phenotypes, allowing a link with evolutionary processes; and (3) it can incorporate the effect of climate at different time periods. We believe that the way climatologists have approached the problem, using atmosphere–ocean coupled circulation models in which components are gradually included and linked to each other, can provide a valuable example to ecologists. We hope that ecologists will take up this challenge and that our preliminary modeling framework will stimulate research toward a unifying predictive model of the ecological consequences of climate change

Oxidative Stress Mediates Physiological Costs of Begging in Magpie (Pica pica) Nestlings

[Background] Theoretical models predict that a cost is necessary to guarantee honesty in begging displays given by offspring to solicit food from their parents. There is evidence for begging costs in the form of a reduced growth rate and immunocompetence. Moreover, begging implies vigorous physical activity and attentiveness, which should increase metabolism and thus the releasing of pro-oxidant substances. Consequently, we predict that soliciting offspring incur a cost in terms of oxidative stress, and growth rate and immune response (processes that generate pro-oxidants substances) are reduced in order to maintain oxidative balance. [Methodology/Principal Findings] We test whether magpie (Pica pica) nestlings incur a cost in terms of oxidative stress when experimentally forced to beg intensively, and whether oxidative balance is maintained by reducing growth rate and immune response. Our results show that begging provokes oxidative stress, and that nestlings begging for longer bouts reduce growth and immune response, thereby maintaining their oxidative status. [Conclusions/Significance] These findings help explaining the physiological link between begging and its associated growth and immunocompetence costs, which seems to be mediated by oxidative stress. Our study is a unique example of the complex relationships between the intensity of a communicative display (begging), oxidative stress, and life-history traits directly linked to viability.GM-R was supported by the Spanish Government (Ministerio de Ciencia y Tecnología, “Juan de la Cierva” program), and TR was supported by the Consejo Superior de Investigaciones Científicas (CSIC; Proyectos Intramurales Especiales)

Clinical practice: Coeliac disease

Coeliac disease (CD) is an immune-mediated systemic condition elicited by gluten and related prolamines in genetically predisposed individuals and characterised by gluten-induced symptoms and signs, specific antibodies, a specific human leukocyte antigen (HLA) type and enteropathy. The risk of coeliac disease is increased in first-degree relatives, certain syndromes including Down syndrome and autoimmune disorders. It is thought to occur in 1 in 100–200 individuals, but still only one in four cases is diagnosed. Small-bowel biopsy is no longer deemed necessary in a subgroup of patients, i.e. when all of the following are present: typical symptoms or signs, high titres of and transglutaminase antibodies, endomysial antibodies, and HLA-type DQ2 or DQ8. In all other cases, small-bowel biopsy remains mandatory for a correct diagnosis. Therapy consists of a strictly gluten-free diet. This should result in complete disappearance of symptoms and of serological markers. Adequate follow-up is considered essential. Conclusion: Although small-bowel biopsy may be omitted in a minority of patients, small-bowel biopsy is essential for a correct diagnosis of CD in all other cases. Diagnostic work-up should be completed before treatment with gluten-free diet instituted