Anti-food and anti-microbial IgG subclass antibodies in inflammatory bowel disease.

OBJECTIVES: Inflammatory bowel disease (IBD), particularly Crohn's disease (CD), is associated with increased microbial-specific IgG and IgA antibodies, whereas alterations of anti-food antibodies are still disputed. The knowledge about IgG subclass antibodies in IBD is limited. In this study we analysed IgG subclass antibodies specific for nutritional and commensal antigens in IBD patients and controls. METHODS: Serum IgG1, IgG2, IgG3 and IgG4 specific for wheat and milk extracts, purified ovalbumin, Escherichia coli and Bacteroides fragilis lysates and mannan from Saccharomyces cerevisiae were analysed by ELISA in patients with CD (n = 56), ulcerative colitis (UC; n = 29), acute gastroenteritis/colitis (n = 12) as well as non-inflammatory controls (n = 62). RESULTS: Anti-Saccharomyces cerevisiae antibodies (ASCA) of all IgG subclasses and anti-B. fragilis IgG1 levels were increased in CD patients compared to UC patients and controls. The discriminant validity of ASCA IgG2 and IgG4 was comparable with that of ASCA pan-IgG and IgA, whereas it was inferior for ASCA IgG1/IgG3 and anti-B. fragilis IgG1. Complicated CD defined by the presence of perianal, stricturing or penetrating disease phenotypes was associated with increased ASCA IgG1/IgG3/IgG4, anti-B. fragilis IgG1 and anti-E. coli IgG1 levels. Anti-food IgG subclass levels were not different between IBD patients and controls and did not correlate with food intolerance. In contrast to anti-microbial Abs, food-specific IgG responses were predominately of the IgG4 isotype and all food-specific IgG subclass levels correlated negatively with age. CONCLUSION: Our study supports the notion that the adaptive immune recognition of food and commensal antigens are differentially regulated.

Haematopoietic cell-derived Jnk1 is crucial for chronic inflammation and carcinogenesis in an experimental model of liver injury.

BACKGROUND & AIMS: Chronic liver injury triggers complications such as liver fibrosis and hepatocellular carcinoma (HCC), which are associated with alterations in distinct signalling pathways. Of particular interest is the interaction between mechanisms controlled by IKKγ/NEMO, the regulatory IKK subunit, and Jnk activation for directing cell death and survival. In the present study, we aimed to define the relevance of Jnk in hepatocyte-specific NEMO knockout mice (NEMO(Δhepa)), a genetic model of chronic inflammatory liver injury. METHODS: We generated Jnk1(-/-)/NEMO(Δhepa) and Jnk2(-/-)/NEMO(Δhepa) mice by crossing NEMO(Δhepa) mice with Jnk1 and Jnk2 global deficient animals, respectively, and examined the progression of chronic liver disease. Moreover, we investigated the expression of Jnk during acute liver injury, evaluated the role of Jnk1 in bone marrow-derived cells, and analysed the expression of NEMO and p-JNK in human diseased-livers. RESULTS: Deletion of Jnk1 significantly aggravated the progression of liver disease, exacerbating apoptosis, compensatory proliferation and carcinogenesis in NEMO(Δhepa) mice. Conversely, Jnk2(-/-)/NEMO(Δhepa) displayed hepatic inflammation. By using bone marrow transfer, we observed that Jnk1 in haematopoietic cells had an impact on the progression of chronic liver disease in NEMO(Δhepa) livers. These findings are of clinical relevance since NEMO expression was downregulated in hepatocytes of patients with HCC whereas NEMO and p-JNK were expressed in a large amount of infiltrating cells. CONCLUSIONS: A synergistic function of Jnk1 in haematopoietic cells and hepatocytes might be relevant for the development of chronic liver injury. These results elucidate the complex function of Jnk in chronic inflammatory liver disease.

Prospective assessment of the quality of life and nipple sensation after gender-affirming chest surgery.

BACKGROUND: In the existing literature, assessing transgender patients' quality of life after surgery, especially using standardized surveys, is rare. The nipple sensation regarding the operating technique has neither been studied in a prospective nor standardized way. METHODS: For one year, we prospectively assessed transgender patients operated on for a gender-affirming chest surgery in our unit. Each patient answered the BREAST-Q© survey and the BODY-Q© chest module survey before and six months after the surgery. In addition, a measure of nipple sensation was performed using Semmes-Weinstein monofilaments pre-and post-operatively to compare surgical techniques. RESULTS: Fifty-one patients (102 breasts) were included in our study. The average age was 23.1 years and the average BMI was 24.8 kg/m2. Twenty-one patients (45%) had double incision and free nipple graft mastectomy, 14 (27%) patients had double incision and inferior pedicle mastectomy, while the 14 (27%) other patients had a semi-circular technique. Our study shows an improvement in all the scores of the surveys after surgery (p < 0.0001). Patients with double incision and inferior pedicle mastectomies rated a significantly higher satisfaction with nipples (p = 0.013) and significantly better sexual well-being (p = 0.007) than other techniques. In addition, preservation of nipple sensation was shown in patients operated by semi-circular technique (p < 0.001) and inferior pedicle technique (p < 0.0001). CONCLUSIONS: Our prospective study confirms the significant improvement in the quality of life of transgender patients after chest gender-affirming surgery. Double incision with inferior pedicle seems to provide better satisfaction with nipples, higher sexual well-being, and preservation of nipple sensation.

How to measure vessel caliber in microsurgery and super-microsurgery? Metrological study of three methods applicable in clinical practice.

INTRODUCTION: The microsurgical literature reports the vascular calibers of the vessels studied even though the method of measurement of these vessels is very rarely reported. MATERIAL AND METHOD: We performed a metrological study evaluating three methods to measure the external calibers of catheters corresponding to microsurgical and super-microsurgical vessels (1.2 mm, 0.8 mm, and 0.6 mm). Six evaluators measured 15 catheters of three different hidden diameters by each of the three methods applicable in clinical practice: standard graduated ruler, Shinwa® micrometric ruler, and ImageJ® software from a photograph. Accuracy and reliability of the measurements were assessed by studying the inter- and intra-rater and inter-method coefficients (variants of the intra-class coefficient (ICC)) and analysis of the IC95% of the ICCs. RESULTS: Intra class correlation ICC "intra-rater" coefficient finds for the standard rule 0.81 [0.65-0.93], Shinwa® rule 0.86 [0.67-0.96], and for the ImageJ® software 0.97 [0.94-0.99]. The "Inter-rater" ICC shows respectively the coefficient 0.51 [0.23 and max 0.93], 0.87 [0.75-0.95], and 0.95 [0.89-0.98]. It appears that the graduated decimeter is the least reliable method of measurement, the Shinwa® ruler presents acceptable reliability but requires the purchase of equipment. The reliability of ImageJ® software is the best and appears to be the most reliable method. CONCLUSION: Our original study, with no equivalent in the scientific literature, demonstrates objectively the great accuracy and reliability of a method of measurement of vascular calibers in micro and super microsurgery using intraoperative photography and the use of free computer software.

Knee Joint Rescue in a Traumatic Amputation With Coverage by a Fillet-Free Flap From the Amputated Leg.

Traumatic amputation is a severe injury that requires urgent surgical care. A fillet-free flap from the amputated limb is the most conservative way to ensure proper coverage of the stump when replantation is not possible. We report the case of a male patient who suffered from a traumatic limb amputation in a motorcycle accident. A free fillet flap from the posterior compartment of the leg carrying the posterior tibial pedicle, the soleus muscle, and skin tissue harvested from the amputated limb was performed to cover the amputation stump and thus allow preservation of the knee joint. In our case report, the patient conserved almost maximal knee joint range of motion (130°). He regained the ability to walk only two months after the initial trauma. Prosthetic fitting occurred quickly and without any particular issues throughout the process. Regarding quality of life, after one year, our patient had a five-level EQ-5D version (EQ-5D-5L) score of 21,221, and his 36-Item Short Form Survey (SF-36) score was divided between the five components in 85 points in physical functioning, 100 points in role limitations due to physical health, 100 points in role limitations due to emotional problems, 50 points in energy/fatigue, 68 points in emotional well-being, 75 points in social functioning, 45 points in pain, and 95 points in general health. This technique helped provide good coverage of the stump while preserving a functional knee joint, allowing for effective prosthetic fitting in the future and therefore optimizing our patient's quality of life.

Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells.

Myasthenia Gravis (MG) is a neurological autoimmune disease characterized by disabling muscle weaknesses due to anti-acetylcholine receptor (AChR) autoantibodies. To gain insight into immune dysregulation underlying early-onset AChR+ MG, we performed an in-depth analysis of peripheral mononuclear blood cells (PBMCs) using mass cytometry. PBMCs from 24 AChR+ MG patients without thymoma and 16 controls were stained with a panel of 37 antibodies. Using both unsupervised and supervised approaches, we observed a decrease in monocytes, for all subpopulations: classical, intermediate, and non-classical monocytes. In contrast, an increase in innate lymphoid cells 2 (ILC2s) and CD27- γδ T cells was observed. We further investigated the dysregulations affecting monocytes and γδ T cells in MG. We analyzed CD27- γδ T cells in PBMCs and thymic cells from AChR+ MG patients. We detected the increase in CD27- γδ T cells in thymic cells of MG patients suggesting that the inflammatory thymic environment might affect γδ T cell differentiation. To better understand changes that might affect monocytes, we analyzed RNA sequencing data from CD14+ PBMCs and showed a global decrease activity of monocytes in MG patients. Next, by flow cytometry, we especially confirmed the decrease affecting non-classical monocytes. In MG, as for other B-cell mediated autoimmune diseases, dysregulations are well known for adaptive immune cells, such as B and T cells. Here, using single-cell mass cytometry, we unraveled unexpected dysregulations for innate immune cells. If these cells are known to be crucial for host defense, our results demonstrated that they could also be involved in autoimmunity.

Antibody-mediated neutralization of galectin-3 as a strategy for the treatment of systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune, inflammatory and fibrotic disease with limited treatment options. Developing new therapies is therefore crucial to address patient needs. To this end, we focused on galectin-3 (Gal-3), a lectin known to be associated with several pathological processes seen in SSc. Using RNA sequencing of whole-blood samples in a cross-sectional cohort of 249 patients with SSc, Gal-3 and its interactants defined a strong transcriptomic fingerprint associated with disease severity, pulmonary and cardiac malfunctions, neutrophilia and lymphopenia. We developed new Gal-3 neutralizing monoclonal antibodies (mAb), which were then evaluated in a mouse model of hypochlorous acid (HOCl)-induced SSc. We show that two of these antibodies, D11 and E07, reduced pathological skin thickening, lung and skin collagen deposition, pulmonary macrophage content, and plasma interleukin-5 and -6 levels. Moreover, E07 changed the transcriptional profiles of HOCl-treated mice, resulting in a gene expression pattern that resembled that of control mice. Similarly, pathological pathways engaged in patients with SSc were counteracted by E07 in mice. Collectively, these findings demonstrate the translational potential of Gal-3 blockade as a therapeutic option for SSc.

Reduced expression of FOXP3 and regulatory T-cell function in severe forms of early-onset autoimmune enteropathy.

BACKGROUND & AIMS: Little is known about the pathophysiology of early onset forms of autoimmune enteropathy (AIE). AIE has been associated with mutations in FOXP3-a transcription factor that controls regulatory T-cell development and function. We analyzed the molecular basis of neonatal or early postnatal AIE using clinical, genetic, and functional immunological studies. METHODS: Gastroenterological and immunological features were analyzed in 9 boys and 2 girls with AIE that began within the first 5 months of life. FOXP3 and IL2RA were genotyped in peripheral blood monocytes. FOXP3 messenger RNA and protein expression were analyzed using reverse-transcription polymerase chain reaction, flow cytometry, and confocal immunofluorescence of CD4(+) T cells. Regulatory T-cell function (CD4(+)CD25(+)) was assayed in coculture systems. RESULTS: AIE associated with extraintestinal autoimmunity was severe and life-threatening; all patients required total parenteral nutrition. Regulatory T cells from 7 patients had altered function and FOXP3 mutations that resulted in lost or reduced FOXP3 protein expression; 2 infants had reduced regulatory T-cell activity and reduced levels of FOXP3 protein, although we did not detect mutations in FOXP3 coding region, poly-A site, or promoter region (called FOXP3-dependent AIE). Two patients had a normal number of regulatory T cells that expressed normal levels of FOXP3 protein and normal regulatory activity in in vitro coculture assays (called FOXP3-independent AIE). No mutations in IL2RA were found. CONCLUSIONS: Most cases of AIE are associated with alterations in regulatory T-cell function; some, but not all, cases have mutations that affect FOXP3 expression levels. Further studies are needed to identify mechanisms of AIE pathogenesis.

Defective IL10 signaling defining a subgroup of patients with inflammatory bowel disease.

OBJECTIVES: Early onset inflammatory bowel diseases (EO-IBD) developing during the first year of life are likely to reflect inherited defects in key mechanism(s) controlling intestinal homeostasis, as recently suggested for interleukin 10 (IL10). Thus, we aimed to further elaborate the hypothesis of defective anti-inflammatory responses in patients with IBD. METHODS: The capacities of transforming growth factor ß (TGFß) and IL10 to inhibit proinflammatory cytokine production by monocyte-derived dendritic cells (MoDC) or peripheral blood cells (PBMC) was analyzed in 75 children with IBD, including 13 infants with EO-IBD (in whom autoimmune diseases or classical immunodeficiencies were ruled out). IL10 receptor-A/-B expression, STAT3 activation in response to IL6, IL10, IL21, IL22 were analyzed by FACS and western blotting. IL10RA and B genes were sequenced. The response to IL22 was tested in ileal/colonic tissue cultures. Tissue gene expression was analyzed by Taqman real-time polymerase chain reaction. RESULTS: Production of IL10 in response to bacterial motifs was normal in all IBD patients. In contrast to our original hypothesis, no defect of the anti-inflammatory potential of TGFß and IL10 was observed in children with IBD or EO-IBD except two infants who presented with granuloma-positive colitis at 3 months of life: no response to IL10 was observed secondary to mutations in the α (p.R262C) or ß (p.E141X) chain of IL10R, respectively, although a fully functional Jak-STAT3 pathway was present in both patients. When analyzing the regulation of intestinal bacterial clearance, we detected a defect in the patient with absent IL10 RB to upregulate protective transcripts in response to IL22, whereas all other EO-IBD patients, including the patient with an abnormal α chain, responded normally. CONCLUSIONS: Impaired IL10 signaling characterizes a subgroup of IBD patients, whereas the majority of children with severe IBD including EO forms normally produces and responds to IL10. Defective IL22 signaling may additionally impair intestinal epithelial clearance. Our data point out the complexity of IBD, which represent a group of distinct diseases with several pathogenetic abnormalities.

Comparative Analysis of Thymic and Blood Treg in Myasthenia Gravis: Thymic Epithelial Cells Contribute to Thymic Immunoregulatory Defects.

The thymus is involved in autoimmune Myasthenia gravis (MG) associated with anti-acetylcholine (AChR) antibodies. In MG, thymic regulatory T cells (Treg) are not efficiently suppressive, and conventional T cells (Tconv) are resistant to suppression. To better understand the specific role of the thymus in MG, we compared the phenotype and function of peripheral and thymic Treg and Tconv from controls and MG patients. Suppression assays with thymic or peripheral CD4 + T cells showed that the functional impairment in MG was more pronounced in the thymus than in the periphery. Phenotypic analysis of Treg showed a significant reduction of resting and effector Treg in the thymus but not in the periphery of MG patients. CD31, a marker lost with excessive immunoreactivity, was significantly reduced in thymic but not blood resting Treg. These results suggest that an altered thymic environment may explain Treg differences between MG patients and controls. Since thymic epithelial cells (TECs) play a major role in the generation of Treg, we co-cultured healthy thymic CD4 + T cells with control or MG TECs and tested their suppressive function. Co-culture with MG TECs consistently hampers regulatory activity, as compared with control TECs, suggesting that MG TECs contribute to the immune regulation defects of MG CD4 + T cells. MG TECs produced significantly higher thymic stromal lymphopoietin (TSLP) than control TECs, and a neutralizing anti-TSLP antibody partially restored the suppressive capacity of Treg derived from co-cultures with MG TECs, suggesting that TSLP contributed to the defect of thymic Treg in MG patients. Finally, a co-culture of MG CD4 + T cells with control TECs restored numbers and function of MG Treg, demonstrating that a favorable environment could correct the immune regulation defects of T cells in MG. Altogether, our data suggest that the severe defect of thymic Treg is at least partially due to MG TECs that overproduce TSLP. The Treg defects could be corrected by replacing dysfunctional TECs by healthy TECs. These findings highlight the role of the tissue environment on the immune regulation.

Faecal Micro-RNAs in Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: Faecal biomarkers are used as indicators of disease activity in inflammatory bowel diseases [IBD], which include Crohn's disease [CD] and ulcerative colitis [UC]. Micro-RNAs [miRNAs] are small non-coding RNAs detectable in extracellular fluids and can be used as clinical biomarkers. The aim of this study was to determine if faecal miRNA composition is altered in IBD. METHODS: More than 800 different human faecal miRNAs were measured in stool samples from control individuals and patients with active CD by using NanoString technology. Selected miRNAs were quantified by qRT-PCR in faeces, serum and intestinal tissue of controls [n = 23] and patients with inactive or active CD [n = 22, n = 22] or UC [n = 11, n = 24] as well as patients with Clostridium difficile infection [CDI, n = 8]. RESULTS: In total, 150 miRNAs were significantly detected in faeces from controls and patients, and multivariate analyses showed that CD patients with high disease activities had a distinct miRNA profile and that miR-223 and miR-1246 were distinct from other faecal miRNAs. In a larger cohort, active UC patients displayed significantly higher levels of miR-223 and miR-1246 than controls while patients with CDI had higher levels of faecal miR-1246 but not miR-223. No differences were noted in serum samples. CONCLUSIONS: To our knowledge, this is the first comprehensive screen of faecal miRNAs performed in IBD. Further investigation will aim to confirm these findings in a larger cohort and to understand the biological function and cellular sources of faecal miRNAs.

Subcellular antigen localization in commensal E. coli is critical for T cell activation and induction of specific tolerance.

Oral tolerance to soluble antigens is critically important for the maintenance of immunological homeostasis in the gut. The mechanisms of tolerance induction to antigens of the gut microbiota are still less well understood. Here, we investigate whether the subcellular localization of antigens within non-pathogenic E. coli has a role for its ability to induce antigen-specific tolerance. E. coli that express an ovalbumin (OVA) peptide in the cytoplasm, at the outer membrane or as secreted protein were generated. Intestinal colonization of mice with non-pathogenic E. coli expressing OVA at the membrane induced the expansion of antigen-specific Foxp3+ Tregs and mediated systemic immune tolerance. In contrast, cytoplasmic OVA was ignored by antigen-specific CD4+ T cells and failed to induce tolerance. In vitro experiments revealed that surface-displayed OVA of viable E. coli was about two times of magnitude more efficient to activate antigen-specific CD4+ T cells than soluble antigens, surface-displayed antigens of heat-killed E. coli or cytoplasmic antigen of viable or heat-killed E. coli. This effect was independent of the antigen uptake efficiency in dendritic cells. In summary, our results show that subcellular antigen localization in viable E. coli strongly influences antigen-specific CD4+ cell expansion and tolerance induction upon intestinal colonization.

Pathophysiological mechanisms of autoimmunity.

Autoimmune diseases (AIDs) are chronic disorders characterized by inflammatory reactions against self-antigens that can be either systemic or organ specific. AIDs can differ in their epidemiologic features and clinical presentations, yet all share a remarkable complexity. AIDs result from an interplay of genetic and epigenetic factors with environmental components that are associated with imbalances in the immune system. Many of the pathogenic mechanisms of AIDs are also implicated in myasthenia gravis (MG), an AID in which inflammation of the thymus leads to a neuromuscular disorder. Our goal here is to highlight the similarities and differences between MG and other AIDs by reviewing the common transcriptome signatures and the development of germinal centers and by discussing some unresolved questions about autoimmune mechanisms. This review will propose hypotheses to explain the origin of regulatory T (Treg ) cell defects and the causes of chronicity and specificity of AIDs.

Management of finger deep burns: The interest of local flaps.

INTRODUCTION: The management of finger deep burns is still problematic for the surgeon. Due to the fineness and the thickness of the subcutaneous tissue, after excision there is an important risk of exposure of the underlying tissue like bone, nerve or tendons. Local flaps (random pattern flap and pedicle flap) allowed ensuring a good quality covering with a tissue with many advantages (good thickness, sensitivity). On the contrary of all other techniques, flaps can be used independently from the vascular quality of the wound bed. Despite those advantages, the literature is poor to report the experience of flap in the management of finger deep burn. MATERIAL AND METHODS: We report our experience in the use of such technique with a series of 49 flaps. The cohort consisted of 34 patients (22 men and 12 women) who were treated in our unit between 2003 and 2012. RESULTS: Of the 49 flaps made, 71,4% were homodactyl flaps. 22,5% were heterodactyl flaps and 6,1% were intermetacarpian (second space) flaps. The rate of success was 87,8%. We reviewed 16 patients out of 34 patients operated, 20 of the 49 flaps performed (40,8%). The patients were reviewed by an independent surgeon. The average follow-up at this consultation was 4,25±2,46 years. The monofilament test was positive for 17 flaps (85% of cases). For the Weber's test, we found a normal perception threshold for 11 flaps (55%), with an average test at 2,8mm (2-4mm). Normal motricity was found at the donor site in 14 of the 16 patients evaluated for 18 of the 20 revised flaps (90% of cases). In terms of cosmetic result, the average overall score obtained at the patient's own evaluation was 0.85. That obtained by the evaluator was equal to 0.55, with no significant difference (scale range from 0 best results to 5 worse results). DISCUSSION: Hand and finger burns are frequent and benefit from rapid, high-quality coverage, enabling early mobilization to combat secondary stiffness problems. The high success rate of our series, as well as the quality of the functional and cosmetic results obtained, demonstrate the reliability and the interest of the digital flaps.

Biliary Mucosal Barrier and Microbiome.

BACKGROUND: The biliary system is in continuous contact with the complex microbiota of the intestine. Microbial products have recently been proposed as potential triggers for biliary diseases. METHODS: The aim of this review is to provide a summary of the current knowledge regarding the role of the biliary and intestinal microbiome in biliary inflammatory diseases. RESULTS: Previously, it was suggested that the healthy biliary system is a sterile organ, while acute cholangitis and cholecystitis may occur from ascending infections. Although non-inflammatory biliary colonization by certain bacteria such as Salmonella spp. has been already recognized since several decades, human and animal studies indicated only very recently that the gallbladder harbors a complex microbiota also under non-pathologic conditions. Novel findings suggested that - similar to the situation in the intestine - the biliary mucosa features a chemical, mechanical, and immunological barrier, ensuring immunological tolerance against commensals. However, microbial triggers might influence acute and chronic inflammatory disease of the biliary system and the whole liver. CONCLUSION: Although yet undefined, dysbiosis of the biliary or intestinal microbiota rather than a single microorganism may influence disease progression.

Distinct patterns of IgG and IgA against food and microbial antigens in serum and feces of patients with inflammatory bowel diseases.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with a defective intestinal barrier and enhanced adaptive immune responses against commensal microbiota. Immune responses against food antigens in IBD patients remain poorly defined. METHODS: IgG and IgA specific for food and microfloral antigens (wheat and milk extracts; purified ovalbumin; Escherichia coli and Bacteroides fragilis lysates; mannan from Saccharomyces cerevisiae) were analyzed by ELISA in the serum and feces of patients with Crohn's disease (CD; n = 52 for serum and n = 20 for feces), ulcerative colitis (UC; n = 29; n = 17), acute gastroenteritis/colitis (AGE; n = 12; n = 9) as well as non-inflammatory controls (n = 61; n = 39). RESULTS: Serum anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-B. fragilis IgG and IgA levels were increased in CD patients whereas antibody (Ab) levels against E. coli and food antigens were not significantly different within the patient groups and controls. Subgroup analysis revealed that CD patients with severe diseases defined by stricturing and penetrating lesions have slightly higher anti-food and anti-microbial IgA levels whereas CD and UC patients with arthropathy have decreased anti-food IgG levels. Treatment with anti-TNF-α Abs in CD patients was associated with significantly decreased ASCA IgG and IgA and anti-E. coli IgG. In the feces specific IgG levels against all antigens were higher in CD and AGE patients while specific IgA levels were higher in non-IBD patients. Anti-food IgG and IgA levels did not correlate with food intolerance. SUMMARY: In contrast to anti-microbial Abs, we found only minor changes in serum anti-food Ab levels in specific subgroups of IBD patients. Fecal Ab levels towards microbial and food antigens show distinct patterns in controls, CD and UC patients.

Molecular mechanisms and cell targets of Th17 cells in the gastrointestinal tract: an innate sense of adaptivity.

T-helper (TH) 17 activation is crucial for protective immune responses against bacteria and fungi at mucosal surfaces, but it can also be implicated in the pathogenesis of several autoimmune and chronic inflammatory diseases, such as inflammatory bowel diseases (IBD). Although rapid progress was made elucidating induction and functional heterogeneity of Th17 responses, the underlying molecular effects of Th17 response including the most relevant different cell targets of Th17 cytokines remain poorly understood. Cytokines produced by Th17 cells have broad effects on both hematopoietic and nonhematopoietic cells and can act in synergy with various inflammatory factors. In this review, we will focus on the effects of Th17-derived cytokines in the gastrointestinal tract and discuss how Th17 responses can affect both innate and adaptive immunity and may contribute to the pathogenesis of inflammatory GI processes.

Specific IgG response against Mycobacterium avium paratuberculosis in children and adults with Crohn's disease.

BACKGROUND AND AIMS: Presence of serum antibodies against Mycobacterium avium paratuberculosis (MAP) in Crohn's Disease (CD) as a disease characteristic remains controversial. In the present work, we assessed antibody reactivity of serum and intestinal fluid against four distinct MAP-antigens, including the recently identified MAP-specific lipopentapeptide (L5P). METHODS: Immunoglobulin concentrations and specificity against 3 non MAP-specific antigens: glycosyl-transferase-d (GSD), purified protein derivative from MAP (Johnin-PPD), heparin binding haemagglutinin (MAP-HBHA) and one MAP-specific antigen: synthetic L5P were determined by ELISA in gut lavage fluids from adult controls or patients with CD, and in sera of children or adult controls or patients with CD, ulcerative colitis or celiac disease. RESULTS: Total IgA and IgG concentrations were increased in sera of children with CD but were decreased in sera of adults with CD, thereof specificity against MAP antigens was assessed by normalizing immunoglobulin concentrations between samples. In CD patients, IgG reactivity was increased against the four MAP antigens, including L5P in gut lavage fluids but it was only increased against L5P in sera. By contrast, anti-L5P IgG were not increased in patients with ulcerative colitis or celiac disease. CONCLUSIONS: A significant increase in anti-L5P IgG is observed in sera of children and adults with CD but not in patients with other intestinal inflammatory diseases. Anti-L5P antibodies may serve as serological marker for CD.