Allergic Colitis Research Articles

Bergenin, the main active ingredient of Bergenia purpurascens, attenuates Th17 cell differentiation by downregulating fatty acid synthesis.

Bergenin is the main active ingredient of Bergenia purpurascens, a medicinal plant which has long been used to treat a variety of Th17 cell-related diseases in China, such as allergic airway inflammation and colitis. This study aimed to uncover the underlying mechanisms by which bergenin impedes Th17 cell response in view of cellular metabolism. Invitro, bergenin treatment reduced the frequency of Th17 cells generated from naïve CD4+ T cells of mice. Mechanistically, bergenin preferentially restrained fatty acid synthesis (FAS) but not other metabolic pathways in differentiating Th17 cells, and exogenous addition of either palmitic acid (PA) or oleic acid (OA) and combination with acetyl-CoA carboxylase 1 (ACC1) activator citric acid dampened the inhibition of bergenin on Th17 cell differentiation. Bergenin inhibited FAS through downregulating the expression of SREBP1 via restriction of histone H3K27 acetylation in the SREBP1 promoter, and SREBP1 overexpression weakened the inhibition of bergenin on Th17 differentiation. Furthermore, bergenin was shown to directly interact with SIRT1 and result in activation of SIRT1. Either combination with SIRT1 inhibitor EX527 or point mutation plasmid of SIRT1 diminished the inhibitory effect of bergenin on FAS and Th17 cell differentiation. Finally, the inhibitory effect of bergenin on Th17 cell response and SIRT1 dependence were verified in mice with dextran sulfate sodium-induced colitis. In short, bergenin repressed Th17 cell response by downregulating FAS via activation of SIRT1, which might find therapeutic use in Th17 cell-related diseases.

Protection against DSS-induced colitis in mice through FcεRIα deficiency: the role of altered Lactobacillus

The role of mast cells (MCs) in ulcerative colitis (UC) development is controversial. FcεRI, the IgE high-affinity receptor, is known to activate MCs. However, its role in UC remains unclear. In our study, Anti-FcεRI showed highly diagnostic value for UC. FcεRIα knockout in mice ameliorated DSS-induced colitis in a gut microbiota-dependent manner. Increased Lactobacillus abundance in FcεRIα deficient mice showed strongly correlation with the remission of colitis. RNA sequencing indicated activation of the NLRP6 inflammasome pathway in FcεRIα knockout mice. Additionally, Lactobacillus plantarum supplementation protected against inflammatory injury and goblet cell loss, with activation of the NLRP6 inflammasome during colitis. Notably, this effect was absent when the strain is unable to produce lactic acid. In summary, colitis was mitigated in FcεRIα deficient mice, which may be attributed to the increased abundance of Lactobacillus. These findings contribute to a better understanding of the relationship between allergic reactions, microbiota, and colitis.

A personalized approach to the management of breastfed infants with functional gastrointestinal disorders and cow’s milk allergy. The role of nutritional recommendations for a nursing mother

Introduction. Functional gastrointestinal disorders (FGID) in infants are a complex of symptoms from the gastrointestinal tract that cannot be explained by structural or biochemical disorders. To alleviate the symptoms of functional disorders, a set of measures is required, first of all, psychological support for the mother and, of course, rational feeding, which includes maintaining breastfeeding, optimizing the nutrition of the nursing mother. Despite the abundance of professional information on this issue, previous studies demonstrate a low level of women’s awareness of nutrition during breastfeeding. The aim of the work is to determine the effectiveness of recommendations on nursing mother’s nutrition in the complex treatment of breastfed children with FGID and allergy to cow’s milk proteins.
 Materials and methods. Seventy five mother–child pairs were included in the study. 1–4 months infants exclusively breastfed during the study were divided into two groups: 1 — FGID infants (n = 51) and 2 — infants with suspected cow’s milk allergy (CMA) n = 24. In addition to the comprehensive treatment of the child, mothers of both groups were given recommendations on the nursing woman’s nutrition. Mothers of children from group 2 were assigned a diagnostic dairy-free diet for a period of 1 month. 
 Results. On the 2nd visit, when analyzing the symptoms of the FGID in group 1, the number of children with symptoms of regurgitation of more than 2 episodes per day decreased by 28% (p < 0.001), crying for more than 3 hours per day — by 52% (p < 0.001). Children of group 2 with a clear positive effect from the diagnostic dairy-free diet therapy of the mother (n = 20) were diagnosed with Allergic and alimentary gastroenteritis and colitis (K52.2 — 10th revision of ICD-10), the continuation of the dairy-free diet for the mother and the supervision of an allergist were prescribed. The survey of women showed that all nursing women were interested in nutrition issues during lactation, 92% of the surveyed mothers searched for this information on the Internet. At the same time, only 12% of women considered this information to be sufficient. Evaluating the presented materials on nutrition, the overwhelming majority of respondents replied that they helped them to adjust their diet and expand nutrition, as well as to maintain breastfeeding.
 Conclusion. Thus, an integrated approach in the management of FGID infants and gastrointestinal manifestations of food allergies, including the use of nutrition recommendations developed in the National Medical Research Center of Children’s Health for nursing women, allows achieving a positive effect on the side of symptoms both in FGID and CMA patients, and also contributes to the improvement of the psycho-emotional state of a woman and prolonged breastfeeding.

Cow’s Milk Protein Intolerance in A Young Infant, Can It Be Cured

Cow's milk protein allergy (CMPA) frequently occurs in the first year of life, with a prevalence of 23% in the infant population. Food protein-induced enterocolitis syndrome (FPIES) is a severe non-IgE (immunoglobin E) presentation—mediated food allergy, which CMPA frequently causes. FPIES is frequently misdiagnosed initially due to its non-specific symptoms and laboratory findings. We present a case of a three-month-old male infant with allergic colitis due to CMPA. The patient was initially diagnosed with infectious colitis, which was then found to be allergic. The patient also did not tolerate extensively hydrolyzed formula and needed amino acid formula. The patient was discharged home in a stable condition. This research implies an increase in awareness and health education among parents, especially those with young infants. The findings of this study can also have an impact on changes in healthcare services and encourage the development of substitute milk products more suitable for infants with cow's milk protein intolerance.

A case of Familial Mediterranean Fever presented with recurrent infection.

The periodic fever syndrome Familial Mediterranean Fever (FMF) is caused by mutations in MEFV, which promote inflammation and present with uncontrolled systemic and organ-specific inflammation that can resemble infectious conditions. It is diagnosed based on clinical criteria, including frequent symptoms such as abdominal and thoracic pain, family history, and response to treatment with colchicine, which is confirmed by genetic assessment. Herein, we present a case of FMF with a relatively uncommon presentation. A 22-month-old female was referred to the allergy and clinical immunology clinic with eczematoid skin rashes. She was admitted to the hospital several times since the 2nd day of life with different complaints like fever, seizure, and restlessness, and treated with the diagnosis of septicemia. Endoscopy and colonoscopy were done at the age of 6 months due to poor weight gain and bloody diarrhea, which revealed active crypt-destructive colitis with foci of erosion in favor of infectious or allergic colitis. The colon biopsy was negative for Cytomegalovirus (CMV). Regarding family history, she was the second child of the first cousins parents and had a healthy 12-year-old sister. There was a history of death for unknown reasons of her cousin, whose parents were related. The immunologic evaluation was done, which showed a relatively normal immunoglobulin level, antibody response, flow cytometry, and lymphocyte transformation test. Nonetheless, a genetic study was done, which showed a homozygote mutation in exon 10 of the MEFV gene in the patient and a heterozygote mutation in both her parents. The periodic fever syndrome Familial Mediterranean Fever (FMF) is caused by mutations in MEFV, which promote inflammation and present with uncontrolled systemic and organ-specific inflammation that can resemble infectious conditions. The patient was diagnosed with FMF, and treatment was started using colchicine, which successfully controlled the patient's symptoms and prevented the recurrence of fever and other inflammatory manifestations.

Regulation of short-chain fatty acids in the immune system.

A growing body of research suggests that short-chain fatty acids (SCFAs), metabolites produced by intestinal symbiotic bacteria that ferment dietary fibers (DFs), play a crucial role in the health status of symbiotes. SCFAs act on a variety of cell types to regulate important biological processes, including host metabolism, intestinal function, and immune function. SCFAs also affect the function and fate of immune cells. This finding provides a new concept in immune metabolism and a better understanding of the regulatory role of SCFAs in the immune system, which impacts the prevention and treatment of disease. The mechanism by which SCFAs induce or regulate the immune response is becoming increasingly clear. This review summarizes the different mechanisms through which SCFAs act in cells. According to the latest research, the regulatory role of SCFAs in the innate immune system, including in NLRP3 inflammasomes, receptors of TLR family members, neutrophils, macrophages, natural killer cells, eosinophils, basophils and innate lymphocyte subsets, is emphasized. The regulatory role of SCFAs in the adaptive immune system, including in T-cell subsets, B cells, and plasma cells, is also highlighted. In addition, we discuss the role that SCFAs play in regulating allergic airway inflammation, colitis, and osteoporosis by influencing the immune system. These findings provide evidence for determining treatment options based on metabolic regulation.

Fecal calprotectin levels in pediatric cow's milk protein allergy.

IntroductionThe most prevalent food allergy in younger children is cow's milk protein allergy (CMPA), a hypersensitivity reaction to cow's milk protein and its most common clinical manifestation is allergic colitis. The goal of our recent study was to assess somatic symptoms of CMPA and to prospectively observe the effects of a dairy elimination diet using objective parameters and questionnaires.MethodsThe County Hospital in Szekszárd, Hungary, investigated children aged 1 to 18 who had clinical signs that might indicate CMPA. Stool samples were taken and analyzed using a fecal calprotectin (FC) rapid test (Quantum Blue fCAL, Bühlmann Laboratories, Switzerland) at the time of the diagnosis and following 3 months of an elimination diet. At the baseline visit as well as the first and second follow-up, questionnaires were filled out. Patients were divided into two subgroups according to dietary guidelines based on the results of the questionnaires.ResultsA total of 47 patients participated in the study [42.55% female, mean age: 7.36 (SD 4.22) years]. There was no significant difference in FC levels between baseline and after 3-month elimination diet [73.98 (71.12) μg/g and 68.11 (74.4) μg/g, respectively, p = 0.331]. After three months, there was a significant decrease in FC levels among patients who adhered to the strict diet [84.06 (79.48) μg/g and 41.11 (34.24) μg/g, respectively, p = 0.001].ConclusionThe findings of our study suggest that FC can be an objective marker in confirming the diagnosis of CMPA. Significant improvement in clinical symptoms and in FC levels can only be expected after a strictly followed elimination diet.

Mechanism of Peitu Shengjin Formula Shenlingbaizhu Powder in Treating Bronchial Asthma and Allergic Colitis through Different Diseases with Simultaneous Treatment Based on Network Pharmacology and Molecular Docking.

Background Shenlingbaizhu powder (SLBZP), one of the classic Earth-cultivating and gold-generating prescriptions of traditional Chinese medicine, is widely used to treat various diseases. However, the pharmacological mechanisms of SLBZP on bronchial asthma (BA) and allergic colitis (AC) remain to be elucidated. Methods Network pharmacology and molecular docking technology were used to explore the potential mechanism of SLBZP in treating BA and AC with the simultaneous treatment of different diseases. The potential active compounds of SLBZP and their corresponding targets were obtained from BATMAN-TCM, ETCM, SymMap TCM@TAIWAN, and TCMSP databases. BA and AC disease targets were collected through DisGeNET, TTD, GeneCards, PharmGKB, OMIM, NCBI, The Human Phenotype Ontology, and DrugBank databases. Common targets for drugs and diseases were screened by using the bioinformatics and evolutionary genomics platform. The analyses and visualizations of Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of common targets were carried out by R software. The key targets were screened by using the plug-in “cytoHubba” of Cytoscape software, and the “active compound-key target” network was constructed. Molecular docking analysis was performed using AutoDock software. The miRTarBase database was used to predict microRNAs (miRNAs) targeting key targets, and the key target-miRNA network was constructed. Result Through screening, 246 active compounds and 281 corresponding targets were obtained. Common targets were mainly enriched in 2933 biological processes and 182 signal pathways to play the role of treating BA and AC. There were 131 active compounds related to key targets. The results of molecular docking showed that the important active compounds in SLBZP had good binding ability with the key targets. The key target-miRNA network showed that 94 miRNAs were predicted. Conclusion SLBZP has played the role of treating different diseases with the same treatment on BA and AC through the characteristics of multicompound, multitarget, and multipathway of traditional Chinese medicine, which provides a theoretical basis for explaining the mechanism and clinical application of SLBZP treating different diseases with the same treatment in BA and AC.

Features of the quality of life in children with food allergy

Introduction. Food allergy (FA) being a clinically heterogeneous condition, the only treatment for which is a strong elimination diet. The need to exclude one or more foods from the diet, constant monitoring of the diet, anxiety and excitement about the exacerbation of allergic symptoms lead to a significant decrease in the quality of life. Materials and methods. The study included thirty eight 2-7 year children patients with various clinical manifestations of FA (atopic dermatitis, allergic and alimentary colitis, food-borne dermatitis). The comparison group consisted of twenty seven healthy children matched by age. The quality of life in all children was assessed using the Pediatric Quality of Life - PedsQLTM4.0 questionnaire. Results. All FA children patients showed a significant decrease in the quality of life in terms of such indicators as emotional functioning (60.2 in the main group and 83.5 in the comparison group), social functioning (77.9 in the main group and 88.1 in the comparison group), role functioning or kindergarten functioning (FDS) (77.5 in the main group and 84.9 in the comparison group) and psycho-social health (69.3 in the main group and 85.5 in the comparison group). The overall score in assessing the quality of life is significantly lower in the group of FA children (71 in the main group and 87 in the comparison group). Conclusion. To improve the quality of life of children with FA, there is needed a comprehensive individual approach including both psychological support for the child and his family members, and the solution of issues with the provision of «safe» food in children’s educational institutions.

STAT5 Represses a STAT3-Independent Th17-like Program during Th9 Cell Differentiation.

IL-9-producing Th cells, termed Th9 cells, contribute to immunity against parasites and cancers but have detrimental roles in allergic disease and colitis. Th9 cells differentiate in response to IL-4 and TGF-β, but these signals are insufficient to drive Th9 differentiation in the absence of IL-2. IL-2-induced STAT5 activation is required for chromatin accessibility within Il9 enhancer and promoter regions and directly transactivates the Il9 locus. STAT5 also suppresses gene expression during Th9 cell development, but these roles are less well defined. In this study, we demonstrate that human allergy-associated Th9 cells exhibited a signature of STAT5-mediated gene repression that is associated with the silencing of a Th17-like transcriptional signature. In murine Th9 cell differentiation, blockade of IL-2/STAT5 signaling induced the expression of IL-17 and the Th17-associated transcription factor Rorγt. However, IL-2-deprived Th9 cells did not exhibit a significant Th17- or STAT3-associated transcriptional signature. Consistent with these observations, differentiation of IL-17-producing cells under these conditions was STAT3-independent but did require Rorγt and BATF. Furthermore, ectopic expression of Rorγt and BATF partially rescued IL-17 production in STAT3-deficient Th17 cells, highlighting the importance of these factors in this process. Although STAT3 was not required for the differentiation of IL-17-producing cells under IL-2-deprived Th9 conditions, their prolonged survival was STAT3-dependent, potentially explaining why STAT3-independent IL-17 production is not commonly observed in vivo. Together, our data suggest that IL-2/STAT5 signaling plays an important role in controlling the balance of a Th9 versus a Th17-like differentiation program in vitro and in allergic disease.

Schistosome Infection and Schistosome-Derived Products as Modulators for the Prevention and Alleviation of Immunological Disorders.

Parasitic helminths, comprising the flatworms (tapeworms and flukes) and nematodes (roundworms), have plagued humans persistently over a considerable period of time. It is now known that the degree of exposure to these and other pathogens inversely correlates with the incidence of both T helper 1 (Th1)-mediated autoimmunity and Th2-mediated allergy. Accordingly, there has been recent increased interest in utilizing active helminth worm infections and helminth-derived products for the treatment of human autoimmune and inflammatory diseases and to alleviate disease severity. Indeed, there is an accumulating list of novel helminth derived molecules, including proteins, peptides, and microRNAs, that have been shown to exhibit therapeutic potential in a variety of disease models. Here we consider the blood-dwelling schistosome flukes, which have evolved subtle immune regulatory mechanisms that promote parasite survival but at the same time minimize host tissue immunopathology. We review and discuss the recent advances in using schistosome infection and schistosome-derived products as therapeutics to treat or mitigate human immune-related disorders, including allergic asthma, arthritis, colitis, diabetes, sepsis, cystitis, and cancer.

STAT6 Pathway Is Critical for the Induction and Function of Regulatory T Cells Induced by Mucosal B Cells.

B cells could convert naïve T cells into regulatory T cells (so-called Treg-of-B cells) which have the ability to treat animal models of inflammatory diseases, including allergic asthma, collagen-induced arthritis and colitis; however, the mechanisms of Treg-of-B cell generation remain unclear. In this study, we investigated the role of STAT6 in the generation of Treg-of-B (P) cells, which Treg cells were generated by Peyer’s patch B cells (P stands for Peyer’s patch). CD4+CD25- T cells from wild type, STAT6 knockout and IL-4 knockout mice were cocultured with wild type Peyer’s patch B cells for Treg-of-B (P) cell generation. A murine asthmatic model was used to analyze the in vivo regulatory function of Treg-of-B (P) cells. The data demonstrated that STAT6 played a critical role in the generation of Treg-of-B (P) cells, which confirmed with STAT6-deficient T cells and the STAT6 inhibitor AS1517499. When STAT6 was lacking, Treg-of-B (P) cells exerted impaired suppressive ability with decreased LAG3 expression. Furthermore, Peyer’s patch B cells played an essential role in regulatory T cell generation. In the absence of Peyer’s patch B cells, T cells expressed decreased phosphorylated STAT6, which was followed by decreased LAG3 expression and impaired suppressive ability, suggesting that Peyer’s patch B cells provided the critical signal to activate STAT6 phosphorylation in T cells. Moreover, STAT6 deficient Treg-of-B (P) cells could not alleviate inflammation in an animal model of asthma in vivo. IL-4 was downstream of phosphorylated STAT6 and maintained Treg-of-B (P) cell survival with increased expression of Bcl-2 and BclXL. We reported a novel finding that the STAT6-LAG3 signaling axis is important for the induction and function of Treg-of-B (P) cells.

Non-IgE- or Mixed IgE/Non-IgE-Mediated Gastrointestinal Food Allergies in the First Years of Life: Old and New Tools for Diagnosis.

non-IgE and mixed gastrointestinal food allergies present various specific, well-characterized clinical pictures such as food protein-induced allergic proctocolitis, food protein-induced enterocolitis and food protein-induced enteropathy syndrome as well as eosinophilic gastrointestinal disorders such as eosinophilic esophagitis, allergic eosinophilic gastroenteritis and eosinophilic colitis. The aim of this article is to provide an updated review of their different clinical presentations, to suggest a correct approach to their diagnosis and to discuss the usefulness of both old and new diagnostic tools, including fecal biomarkers, atopy patch tests, endoscopy, specific IgG and IgG4 testing, allergen-specific lymphocyte stimulation test (ALST) and clinical score (CoMiss).

RhoA and Cdc42 in T cells: Are they targetable for T cell-mediated inflammatory diseases?

Many inflammatory diseases are not curable, necessitating a better understanding of their pathobiology that may help identify novel biological targets. RhoA and Cdc42 of Rho family small GTPases regulate a variety of cellular functions such as actin cytoskeletal organization, cell adhesion, migration, proliferation, and survival. Recent characterization of mouse models of conditional gene knockout of RhoA and Cdc42 has revealed their physiological and cell type-specific roles in a number of cell types. In T lymphocytes, which play an important role in the pathogenesis of most, if not all, of the inflammatory diseases, we and others have investigated the effects of T cell-specific knockout of RhoA and Cdc42 on T cell development in the thymus, peripheral T cell homeostasis, activation, and differentiation to effector and regulatory T cells, and on T cell-mediated allergic airway inflammation and colitis. Here we highlight the phenotypes resulting from RhoA and Cdc42 deletion in T cells and discuss whether pharmacological targeting of RhoA and Cdc42 is feasible in treating asthma that is driven by allergic airway inflammation and colitis.

Unusual presentation of cow's milk protein allergy in a neonate

Cow's milk protein allergy is the most common food protein allergy in children. We report a neonate on breast feeds and formula feeds presenting on day 9 of life with blood in stools, anemia, shock, respiratory failure with multiorgan dysfunction, and recovered with intensive care. Colonoscopy and biopsy confirmed the diagnosis as allergic colitis. Neonate improved with cow's milk protein-eliminated diet. Food protein allergy can present with protean signs and symptoms; high index of suspicion is needed for the prompt early diagnosis.

Allergic proctocolitis causing hematochezia in preterm twins

Allergic colitis due to cow’s milk or soy protein in commercially prepared infant formula or due to ingestion of breast-milk of mothers who are ingesting cow’s milk is a known cause of colitis occurring in infants. Allergic colitis can occur within days, weeks or months of birth and should be considered as a differential diagnosis in any infant presenting with hematochezia. Typically, there is a significant delay in the onset of milk allergy in premature infants compared to full term infants. We report a case of premature twin neonates who presented with profuse rectal bleeding during second week of life. The infants had been feeding expressed breast milk since birth and the nursing mother had been drinking cow’s milk. The infants had pneumatosis coli suggestive of inflammation of the colon while biochemical and hematological markers of inflammation were normal. Expressed breast milk was re-introduced after eliminating dairy from mother’s diet for 5 days. The infants were fed on mother’s milk and top up of hydrolyzed infant formula as required. Both the twins remained well.

Does faecal calprotectin differentiate between inflammatory bowel disease colitis and non-inflammatory bowel disease colitides?

IntroductionChronic colitis is a major problem worldwide with high morbidity. Causes of chronic colitis are heterogeneous. A cut-off level of faecal calprotectin to predict inflammatory bowel disease (IBD) as a cause of chronic colitis is lacking.AimTo study the level of faecal calprotectin in different causes of colitis and to measure the cut-off level to differentiate between IBD and non-IBD colitides.Material and methodsThis prospective study was conducted from June 2018 to May 2019. The study included all patients aged 2 months up to 18 years who were confirmed to have chronic colitis endoscopically and histopathologically attending the Gastroenterology Clinic at Alexandria University Children’s Hospital. Faecal calprotectin level was measured.ResultsWe included 110 patients. Allergic colitis was the commonest cause followed by IBD followed by infectious colitis (50.9%, 38.1% and 6.3% respectively). Faecal calprotectin above 744 µg/g could predict IBD as a cause of chronic colitis with 86.8% specificity and 66.7% sensitivity. Significant elevation of faecal calprotectin was detected in IBD patients. Faecal calprotectin was significantly correlated with C-reactive protein level and erythrocyte sedimentation rate.ConclusionsFaecal calprotectin could predict the cause of colitis and could aid the paediatrician for early referral of patients with chronic colitis.

Eosinophils adhesion assay as a tool for phenotypic drug screening - The pharmacology of 1,3,5 – Triazine and 1H-indole like derivatives against the human histamine H4 receptor

Histamine is a pleiotropic biogenic amine, having affinity towards four distinct histamine receptors. The existing pharmacological studies suggest the usefulness of histamine H4 receptor ligands in the treatment of many inflammatory and immunomodulatory diseases, including allergic rhinitis, asthma, atopic dermatitis, colitis or pruritus. Up to date, several potent histamine H4 receptor ligands were developed, none of which was registered as a drug yet. In this study, a series of potent indole-like and triazine derivatives were tested, in radioligand displacement and functional assays at histamine H4 receptor, as well as in human eosinophils adhesion assay to endothelium. For selected compounds permeability, cytotoxicity, metabolic and in vivo studies were conducted. Adhesion assay differentiated the activity of different groups of compounds with a known affinity towards the histamine H4 receptor. Most of the tested compounds downregulated the number of adherent cells. However, adhesion assay revealed additional properties of tested compounds that had not been detected in radioligand displacement and aequorin-based functional assays. Furthermore, for some tested compounds, these abnormal effects were confirmed during the in vivo studies. In conclusion, eosinophils adhesion assay uncovered pharmacological activity of histamine H4 receptor ligands that has been later confirmed in vivo, underscoring the value of well-suited cell-based phenotypic screening approach in drug discovery.

Feeding-based treatment of allergic proctocolitis and associated clinical outcomes

Allergic colitis (AC) is one of the most common etiologies of rectal bleeding in infants aged one to six months. The aim of this study is to apply step-by-step dietary restrictions in the mother's diet or change of infant formula fed thereby, to evaluate the subsequent clinical response. Sixty healthy infants whose clinical and evaluation results indicated proctocolitis in our outpatient gastroenterology clinic were included in this. They were divided into three groups according to the type of feeding; group 1 were exclusively breast fed, group 2 were exclusively formula fed and group 3 were fed with combination of both. In breast feeding women, discontinuation was allergenic food was studied in four stages; cow-related dairy products, soy, sesame and fast food (stage A), egg (stage B), corn, nuts and fish (stage C) and wheat (stage D). Sixty newborns with age at symptom onset 3 days-20 days participated in the study. Up to the time of our initial evaluation, the mean age and weight of infants was 73.34±1.00 day and 3292.71±367.93g, respectively. There was no significant difference in sex and the type of labor between the groups. Thirty-three infants had a history of eczema and the parents of 47 infants had a history of allergy, with the greatest prevalence in group one. Rectal bleeding in 50% of infants was halted after the elimination of allergenic feed in mother (15 in stage A, 8 in stage B and 7 in stage C). Ten infants needed extensive hydrolyzed formula and 20 needed amino acid-based formulas. There is no need for immediate use of amino acid or extensive hydrolyzed formulas in the first stage of blood in stool, perhaps discontinuing allergenic food in mothers could be the primary measure.

102 Patients with Primary Autoimmune Neutropenia : An Analysis of the European Severe Chronic Neutropenia International Registry (SCNIR)

Background: Primary Autoimmune Neutropenia (AIN) is the most frequent type of neutropenia in children with a prevalence of 1/100,000 between infancy and 10 years of age. Primary AIN is caused by anti-neutrophil antibodies binding to neutrophil-specific antigens, resulting in a decrease of circulating neutrophils in the blood, but normal numbers of mature neutrophils in the bone marrow. Typically, primary AIN is present from infancy on until spontaneous remission in early childhood, when anti-neutrophil antibodies disappear. Patients with primary AIN show severe to moderate neutropenia but only rarely suffer from serious infections. Patients remain in the registry for follow up after normalization of blood counts to evaluate late secondary events. Aims: Here we describe the cohort of AIN pts with positive anti-neutrophil antibody testing documented by the European Branch of the SCNIR. We analyzed the course of neutropenia, the frequency of G-CSF treatment for AIN, the incidence of severe bacterial infections and administration of AB prophylaxis. Methods: We identified 102 primary AIN patients within the neutropenia cohort documented by the European Branch of the SCNIR since 1994. We classified primary AIN by positive anti-neutrophil antibody testing (95 pts) or severe neutropenia in peripheral blood with normal bone marrow morphology in patients with age under 5 years (7 pts). Results: Primary AIN has been identified in 102 (61 female; 41 male) pts. The median age of the cohort is 5.18 years (range 1.37-22.71 years), with 630.28 pt years under observation. Median age at diagnosis was 12.07 months (range 0.9-70 months). All pts are currently alive, 40 patients already resolved from primary AIN at a median age of 3.02 years (range 0.83-9.08 years). Median follow-up time after neutropenia had resolved was 2.25 years (range 0-9.27 years). Sixteen of 102 pts (15.7%) received intermittent G-CSF treatment with a median dose of 4.5 µg/kg/day compared to 4.77 µg/kg/day for the congenital neutropenia cohort of the SCNIR Europe. Analysis of infections (tab.1) showed less minor and severe infections comparing to congenital neutropenia (CN) pts. Life-threatening infections like liver abscesses were not seen in primary AIN patients but in 1.8% of CN pts. Twelve AIN pts (11.7%) have received antibiotic prophylaxis for prevention of infection, 6 pts intermittent and 6 pts continuously. However, antibiotic prophylaxis was usually stopped before termination of AIN. Due to the milder course of infections most AIN pts were able to go to Kindergarten and to live a normal life. In 3 pts additional auto-immune related diseases were identified (autoimmune thrombocytopenia, allergic colitis and Kawasaki syndrome) during AIN. Sixteen of 102 AIN patients received genetic analysis, with no mutation being detected. In addition to the 102 AIN pts we identified another 31 CN pts who have initially been classified as AIN due to positive anti-neutrophil antibodies, but who were later genetically confirmed as CN (15 ELANE+, 8 HAX1+, 2 SBDS+, 2 CXCR4+, 2 CSF3R+, 1 G6PC3+). This proportion of pts showed more and more severe infections compared to primary AIN. Genetic testing has been performed in these pts due to ongoing infections and prolonged neutropenia until school age. Conclusions: Pts suffering from primary AIN present with severe to moderate neutropenia. A minority of pts might require G-CSF treatment on demand/interventionally due to antibiotic resistant infections, but long-term G-CSF treatment is regularly not indicated. Primary AIN is a self-limiting condition and in most pts neutropenia resolves until early childhood. Accumulation of secondary diagnoses like autoimmune related diseases, though postulated, has not been confirmed for AIN pts by our data. In AIN pts with severe infections, or prolonged neutropenia CN should be ruled out by genetic analysis and/or bone marrow morphology. Registries are needed to document long-term data on primary AIN pts to analyse potential additional features of primary AIN, possibly other accompanying autoimmune diseases. Disclosures No relevant conflicts of interest to declare.