Immune System Abnormalities Research Articles

Novelty in Inflammation and Immunomodulation in Migraine.

Migraine is a diffuse and disabling disease. Its pathophysiology is complex and involves both central and peripheral dysfunctions. This review will discuss the pathogenesis of migraine from the origin of the neuro-inflammatory theory, to the modern pathophysiological model and the latest therapies. PUBMED and EMBASE (up to May 2019) were searched for: migraine, inflammation, immunomodulation. An additional search was carried out from the bibliography of previous review articles. Migraine was thought to be mainly a vascular disorder, according to the so-called "vascular theory". Based on animal models, a new hypothesis called "the neuro-inflammatory" was conceived at the end of the 20th century. The growing knowledge about the trigeminovascular system and its role in the inflammatory-pain pathway, allowed to identify other specific neurotransmitters, such as the Calcitonin Gene-Related Peptide and Pituitary Adenylate Cyclase-Activating Peptide. Evidence was provided that the inflammatory-pain system could become sensitised and, due to this sensitisation, the pain could also perpetuate, even in the absence of any triggers of the migraine attack. At last, brain immune cells modification during cortical spreading depression in migraine was demonstrated, along with the existence and function of the glymphatic system. The better comprehension of the immune system abnormalities allowed the development of new immunomodulating drugs: the monoclonal antibodies against the CGRP or the CGRP receptor. Moreover, new insights into the molecular mechanism of CGRP, and the function of C-fibres and Aδ-fibres, highlighted the mechanism of action of Botulinum Toxin type A in the treatment of chronic migraine.

Expert System of Detection Defisiensi Imun Uses K-Nearest Neighbor Method

Immune deficiency is a collection of various diseases which, due to having one or more immune system abnormalities and impairing the functioning of the immune system that are decreasing or not functioning properly, with this condition the susceptibility to infection increases. This disease is mostly suffered by children, this is because the immune system changes in children who have not been able to deal with immune attenuation attacks. For now the number of children who do not get early treatment properly, this is due to a lack of public knowledge about this skin inflammatory disease. Looking at the problems that have been raised, it is necessary to build an Expert System that is able to move expert knowledge into a system of consultation services to detect Immunodeficiency Disease based on clinical symptoms experienced by applying the K-Nearest Neighbor method which functions to process knowledge so that can conclude disease probabilities that refer to the state of the previous diagnosis to be used as an initial diagnostic analysis

CONGENITAL MYOPATHIES: CENTRONUCLEAR AND OTHERS: P.103STIM1 over-activation generates a multi-systemic phenotype affecting skeletal muscle, spleen, eye, skin, bones, and the immune system in mice

Tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK) are spectra of the same disease affecting muscle, platelets, spleen, and skin. TAM and STRMK arise from gain-of-function mutations in STIM1 or ORAI1, both encoding key regulators of Ca2+ homeostasis, and mutations in either gene results in excessive Ca2+ entry. To elucidate the physiological consequences of STIM1 over-activation, we generated a murine model harboring the most common TAM/STRMK mutation and characterized the phenotype at the histological, ultrastructural, metabolic, physiological, and functional level. In accordance with the clinical picture of TAM/STRMK, the Stim1R304W/+ mice manifested muscle weakness, thrombocytopenia, skin and eye anomalies, and spleen dysfunction, as well as additional features not yet observed in patients such as abnormal bone architecture and immune system dysregulation. In situ force measurements of the Stim1R304W/+ tibialis anterior revealed a reduction of the specific force, and we also measured sustained muscle contraction upon stimulation, demonstrating delayed muscle relaxation. Histological and ultrastructural analyses of Stim1R304W/+ tibialis anterior, soleus and gastrocnemius disclosed mild dystrophic features including internalized nuclei, regenerating fibers, fibrosis, and inflammation, fibers with high Ca2+ content, and swollen mitochondria. Tubular aggregates, the histopathological hallmark of TAM/STRMK were however not seen, demonstrating that they do no contribute to disease development. Ca2+ measurements on differentiated Stim1R304W/+ myotubes revealed elevated basal Ca2+ levels and an increased extracellular Ca2+ entry despite normal Ca2+ stores. Altogether, the Stim1R304W/+ mice recapitulate the main clinical features of TAM/STRMK, and provide insight into the pathophysiological effect STIM1 over-activation and aberrant Ca2+ homeostasis in different cells, tissues, and organs.

Hazardous Effects of Arsenic Contaminated Water on the Biological Characteristics of Fishes: A Review

The aim of the current review is to deliberate on arsenic chemistry, its existence in aquatic ecosystem and its effects on the biological systems of fishes which are regarded as potential indicators for any change in water quality. Water is a major storehouse of arsenic which is present in the form of arsenate and arsenite. Anthropogenic activities including unlimited application of arsenic pesticides, industrial activities and mining operations have increased the universal incidence of soluble arsenic above tolerable levels of 0.010 mg/L. Variations in fish behaviour, growth rate, haematological and biological parameters and organ systems have been observed in arsenic contaminated water. Data regarding these parameters indicate that the fish shows aggressive behaviour and its weight increases due to a high arsenic uptake. The production rate of biochemical compounds like carbohydrates, proteins and lipids is reduced due to arsenic bonding with their precursors. Among organ systems, skin is a highly affected organ, while muscles are the least affected due to high arsenic concentration. Low concentration of arsenic results in bioaccumulation, conspicuously in liver and kidney, upon incessant exposure to freshwater fish. This bioaccumulation turns into biomagnification and becomes the cause of lethal diseases in human beings, such as hyperglycaemia, diminution of enzymatic activities and immune system abnormalities. Keeping in view all of these above mentioned facts, it is imperative to take action against excessive arsenic usage and to develop its eco-friendly management ways.

Heightened levels of antimicrobial response factors in patients with systemic lupus erythematosus

Abstract Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by immune system abnormalities and severe inflammation leading to multi-organ damage. Compromised gut permeability and microbial translocation is suggested to be associated with SLE. The objective of this study was to assess whether SLE subjects have increased systemic exposure to bacteria. Plasma from 30 SLE patients and 30 age and sex matched healthy controls were assessed for a series of clinically relevant antimicrobial response factors (ARFs) including sCD14, EndoCAbs, LBP, lysozyme, CXCL16, FABP2, galectin-3, and LL-37. The levels of sCD14 (P<0.0001), lysozyme (P<0.0001) and CXCL16 (P=0.001) were significantly elevated in SLE subjects compared to healthy controls. sCD14 exhibited a positive correlation with SELENA-SLEDAI score. EndoCAbs are antibodies directed against the endotoxin core of LPS. Interestingly, the ratio of EndoCAb IgM:total IgM was significantly decreased in SLE (P=0.006) and this ratio was negatively correlated with sCD14 levels (P=0.030, r=-0.396). We observed significant positive correlations between lysozyme levels and sCD14 (r=0.499, P=0.005), LBP (r=0.434, P=0.016), and FABP2 (r=0.396, P=0.030). Levels of CXCL16 was also positively correlated with the levels of sCD14 in SLE cohort (r=0.551, P=0.001). Moreover, Galectin-3 levels also positively correlated with lysozyme (r=0.447, P=0.013), sCD14 (r=0.425, P=0.019), and LBP (r=0.416, P=0.022). Overall, these changes in the levels and relationships between ARFs link microbial exposure and SLE. Thus, our study results are relevant to clinical SLE that will help to define better therapeutic strategies for SLE patients.

Infants born to mothers with IBD present with altered gut microbiome that transfers abnormalities of the adaptive immune system to germ-free mice

Background and aimsPrenatal and early life bacterial colonisation is thought to play a major role in shaping the immune system. Furthermore, accumulating evidence links early life exposures to the risk...

Intestinal Immune Dysregulation Driven by Dysbiosis Promotes Barrier Disruption and Bacterial Translocation in Rats With Cirrhosis.

In cirrhosis, intestinal dysbiosis, intestinal barrier impairment, and systemic immune system abnormalities lead to gut bacterial translocation (GBT) and bacterial infection. However, intestinal immune system dysfunction and its contribution to barrier damage are poorly understood. This study correlates immune system dysregulation in the intestines of rats at different stages of CCl4 -induced cirrhosis with barrier function and pathogenic microbiota. The following variables were addressed in the small intestine: intraepithelial lymphocyte (IEL) and lamina propria lymphocyte (LPL) activation status and cytokine production (flow cytometry), cytokine mRNA and protein expression (quantitative real-time PCR and immunofluorescence), microbiota composition of ileum content (16S recombinant DNA massive sequencing), permeability (fecal albumin loss), and epithelial junctions (immunohistochemistry and immunofluorescence). The intestinal mucosa in rats with cirrhosis showed a proinflammatory pattern of immune dysregulation in IELs and LPLs, which featured the expansion of activated lymphocytes, switch to a T helper 1 (Th1) regulatory pattern, and Th17 reduction. In rats with cirrhosis with ascites, this state was associated with epithelial junction protein disruption, fecal albumin loss, and GBT. Direct correlations (P < 0.01) were observed between elevated interferon gamma (IFNγ)-expressing T cytotoxic LPLs and fecal albumin and between inflammatory taxa abundance and IFNγ-producing immune cells in the ileum. Bowel decontamination led to redistributed microbiota composition, reduced proinflammatory activation of mucosal immune cells, normalized fecal albumin levels, and diminished GBT; but there were no modifications in Th17 depletion. Conclusion: The intestinal mucosa of rats with cirrhosis acquires a proinflammatory profile of immune dysregulation that parallels the severity of cirrhosis; this impaired intestinal immune response is driven by gut dysbiosis and leads to disrupted barrier function, promoting GBT.

Use of Ustekinumab in the Treatment of Libyan Psoriasis Vulgaris Patients

Abstract Introduction. Psoriasis is a relatively common chronic inflammatory disease. It clinically manifests as raised, well defined erythematous plaques with irregular borders and silvery scales. Psoriasis appears to be mediated by abnormal immune system functioning, including T lymphocyte and macrophage activation and release of various cytokins, such as interleukin 12 (IL-12) and IL-23. Recently a new biologic agent Ustekinumab has been used in the treatment of psoriasis. Our aim in this study was to assess the efficacy and tolerability of ustekinumab in moderate to severe psoriasis vulgaris and to observe and report any adverse reaction. Material and Methods. Thirty five psoriatic patients above the age of 18 years having moderate to severe psoriasis were included in this study. Ustekinumab is available in pre-filled syringe 45mg/0.5ml, 90mg/1.0ml for subcutaneous injection according to body weight at the intervals of 0, 4 weeks, and then every 12 weeks. It is given in hospital by a doctor or specialist nurse. The assessment of the patients’ condition and improvement was carried out after administering each dose using PASI score. Results. Thirty five patients were included in this study. Baseline PASI score of our patients ranged from 11.4 to 39.8 (mean: 21.1).There was a dramatic response to treatment with ustekinumab in which PASI decreased to 6.7 after the second dose, followed by subsequent responses that reached 2.6 after the 6th dose. After the second dose, 61% of the cases had marked improvement and 11% had clearance of their skin lesions. After the last, sixth dose there was a marked improvement in 65% of cases and the percentage of complete clearance increased to 24%. Ustekinumab had positive effect on psoriatic nail changes as well-there was a significant improvement in 50% of cases and complete clearance (cure) in 24% of cases. Conclusion: Ustekinumab is effective in the treatment of severe and resistant cases of psoriasis vulgaris. It is well tolerated by the patients. No reactions or serious side effects have been reported.

Hemophagocytic Lymphohistiocytosis in Adults: Associated Diagnoses and Outcomes, a Ten-Year Experience at a Single Institution.

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive systemic inflammation which causes tissue damage due to abnormal immune system activation and has a high fatality rate even with treatment. HLH continues to be a difficult diagnosis to make because of lack of awareness and its overlap with other illnesses. This disorder is well defined in pediatric patients under the age of 18, but there is also a paucity of data in the adult population. The goals of this study were to describe associated disorders, clinical course and outcomes, and to determine if additional clinical criteria can be used to help with the diagnosis of HLH in adult patients.MethodsPatients’ electronic medical records from 2007 to 2017 (who were ≥ 18 years old at the time of the search) were screened by ICD 9 and ICD 10 codes which contain the diagnosis of HLH or hemophagocytic syndrome, infection-associated. We identified 41 adult cases of HLH that were treated at our medical center over the course of 10 years and assessed these patients using both the historical and newly proposed diagnostic criteria. We also identified underlying diagnoses related to the development of HLH and fatality rates.ResultsMedian age at diagnosis was 55 years old (18 - 87 years old) and 22 were male. Twenty-two had an infection, 16 with malignancy, seven had an autoimmune disorder and one with Sweet syndrome. Fifteen patients were treated with steroids alone, 18 with steroids and chemotherapy, three with steroids and antiviral agents, and two with chemotherapy alone. Sixteen (39%) died and 25 (60%) survived discharge. Seven patients died after discharge. Median survival of all patients was 1,095 days.ConclusionsOur data show that HLH is primarily associated with infections and malignancies. Newly proposed diagnostic criteria are not as specific, but can be helpful in making the diagnosis of HLH. We also showed that the fatality rate at our institution was lower than currently published rates of adult HLH.

Effect of Panchatikta Panchaprasritika Basti (Medicated Enema Therapy) in the Management of Photodermatoses: A Case Study

Photodermatoses is a skin disease that is caused by exposure to sunlight. People with photodermatoses may develop skin rashes following exposure to the sun. This manifestation is most likely due to an abnormal immune system reaction to the sun. There is no exclusive description for this condition in Ayurveda, but all pathological skin manifestations are described under the heading of Kustha (~skin diseases). As, the symptoms of photodermatoses are predominant in Vata pitta, the condition can be managed accordingly. The present case of Photodermatoses is treated with Panchatikta pancha prasratika basti, topical application of Go-ghrita, and internal administration of Kaishor guggulu and Manjistadi kwatha. Significant relief was found in Kandu (~itching), Daha (~burning sensation), Toda (~pricking sensation), Shyava aruna varnata (~blackish red hyper pigmentation), Rukshata (~dryness), Utsedha (~skin thickening), Srava (~discharge) and Twak nirmochana (~scaling of skin). Considering the satisfactory results in the present case; similar strategies can be adopted in suitable cases of photodermatoses in larger sample size to generate evidences and disseminate usefulness of traditional interventions in the management of photodermatoses.

STIM1 over-activation generates a multi-systemic phenotype affecting the skeletal muscle, spleen, eye, skin, bones and immune system in mice.

Strict regulation of Ca2+ homeostasis is essential for normal cellular physiology. Store-operated Ca2+ entry (SOCE) is a major mechanism controlling basal Ca2+ levels and intracellular Ca2+ store refilling, and abnormal SOCE severely impacts on human health. Overactive SOCE results in excessive extracellular Ca2+ entry due to dominant STIM1 or ORAI1 mutations and has been associated with tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK). Both disorders are spectra of the same disease and involve muscle weakness, myalgia and cramps, and additional multi-systemic signs including miosis, bleeding diathesis, hyposplenism, dyslexia, short stature and ichthyosis. To elucidate the physiological consequences of STIM1 over-activation, we generated a murine model harboring the most common TAM/STRMK mutation and characterized the phenotype at the histological, ultrastructural, metabolic, physiological and functional level. In accordance with the clinical picture of TAM/STRMK, the Stim1R304W/+ mice manifested muscle weakness, thrombocytopenia, skin and eye anomalies and spleen dysfunction, as well as additional features not yet observed in patients such as abnormal bone architecture and immune system dysregulation. The murine muscles exhibited contraction and relaxation defects as well as dystrophic features, and functional investigations unraveled increased Ca2+ influx in myotubes. In conclusion, we provide insight into the pathophysiological effect of the STIM1 R304W mutation in different cells, tissues and organs and thereby significantly contribute to a deeper understanding of the pathomechanisms underlying TAM/STRMK and other human disorders involving aberrant Ca2+ homeostasis and affecting muscle, bones, platelets or the immune system.

Infections in children with autism spectrum disorder: Study to Explore Early Development (SEED).

Immune system abnormalities have been widely reported among children with autism spectrum disorder (ASD), which may increase the risk of childhood infections. The Study to Explore Early Development (SEED) is a multisite case-control study of children aged 30-69 months, born in 2003-2006. Cases are children previously diagnosed and newly identified with ASD enrolled from education and clinical settings. Children with a previously diagnosed non-ASD developmental condition were included in the developmental delay/disorder (DD) control group. The population (POP) control group included children randomly sampled from birth certificates. Clinical illness from infection during the first 28 days ("neonatal," from medical records) and first three years of life (caregiver report) in cases was compared to DD and POP controls; and between cases with and without regression. Children with ASD had greater odds of neonatal (OR = 1.8; 95%CI: 1.1, 2.9) and early childhood infection (OR = 1.7; 95%CI: 1.5, 1.9) compared to POP children, and greater odds of neonatal infection (OR = 1.5; 95%CI: 1.1, 2.0) compared to DD children. Cases with regression had 1.6 times the odds (95%CI: 1.1, 2.3) of caregiver-reported infection during the first year of life compared to cases without regression, but neonatal infection risk and overall early childhood infection risk did not differ. Our results support the hypothesis that children with ASD are more likely to have infection early in life compared to the general population and to children with other developmental conditions. Future studies should examine the contributions of different causes, timing, frequency, and severity of infection to ASD risk. Autism Research 2019, 12: 136-146. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We looked at infections during early childhood in relation to autism spectrum disorder (ASD). We found that children with ASD were more likely to have an infection in the first 28 days of life and before age three compared to children with typical development. Children with ASD were also more likely than children with other developmental delays or disorders to have an infection in the first 28 days of life.

Guidelines for biomarkers in autoimmune rheumatic diseases - evidence based analysis.

Autoimmune rheumatic diseases are characterised by an abnormal immune system response, complement activation, cytokines dysregulation and inflammation. In last years, despite many progresses in managing these patients, it has been shown that clinical remission is reached in less than 50% of patients and a personalised and tailored therapeutic approach is still lacking resulting in a significant gap between guidelines and real-world practice. In this context, the need for biomarkers facilitating early diagnosis and profiling those individuals at the highest risk for a poor outcome has become of crucial interest. A biomarker generally refers to a measured characteristic which may be used as an indicator of some biological state or condition. Three different types of medical biomarkers has been suggested: i. mechanistic markers; ii. clinical disease markers; iii. therapeutic markers. A combination of biomarkers from these different groups could be used for an ideal more accurate diagnosis and treatment. However, although a growing body of evidence is focused on improving biomarkers, a significant amount of this information is not integrated on standard clinical care. The overarching aim of this work was to clarify the meaning of specific biomarkers during autoimmune diseases; their possible role in confirming diagnosis, predicting outcome and suggesting specific treatments.

Early recognition of inflammatory arthritis

The term inflammatory polyarthritis describes a family of diseases, which includes rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis, where abnormal immune system function causes inflammation within joint tissues. We know that early diagnosis of inflammatory polyarthritis improves long-term outcomes significantly; if left untreated inflammation can cause irreversible joint damage and lead to persistent pain and disability. A recent national audit in the UK has shown significant delays in diagnosis of inflammatory arthritis in primary care, with only 16% of patients referred within the target time of 3 working days. It is important that GPs are aware of the key symptoms and signs of inflammatory arthritis, can confidently differentiate inflammatory and mechanical causes of joint pain, and are aware of when urgent referral to rheumatology is appropriate.

Identification of novel immune-relevant drug target genes for Alzheimer's Disease by combining ontology inference with network analysis.

Alzheimer's disease (AD) is one of the leading causes of death in elderly people. Its pathogenesis is greatly associated with the abnormality of immune system. However, only a few immune-relevant AD drug target genes have been discovered up to now, and it is speculated that there are still many potential drug target genes of AD (at least immune-relevant genes) to be discovered. Thus, this study was designed to identify novel AD drug target genes and explore their biological properties. A combinatorial approach was adopted for the first time to discover AD drug targets by collectively considering ontology inference and network analysis. Moreover, a novel strategy limiting the distance of reasoning and in turn reducing noise interference was further proposed to improve inference performance. Potential AD drug target genes were discovered by integrating information of multiple popular databases (TTD, DrugBank, PharmGKB, AlzGene, and BioGRID). Then, the enrichment analyses of the identified drug targets genes based on nine well-known pathway-related databases were conducted to explore the function of the identified potential drug target genes. Eighteen potential drug target genes were finally identified, and 13 of them had been reported to be closely associated with AD. Enrichment analyses of these identified drug target genes, based on nine pathway-related databases, revealed that the enriched terms were primarily focus on immune-relevant biological processes. Four of those identified drug target genes are involved in the classical complement pathway and process of antigen presenting. The well-reproducible results showed the good performance of the combinatorial approach, and the remaining five new targets could be a good starting point for our understanding of the pathogenesis and drug discovery of AD. Moreover, this study supported validity of the combinatorial approach integrating ontology inference with network analysis in the discovery of novel drug target for neurological diseases.

Antidepressant-Resistant Depression in Patients With Comorbid Subclinical Hypothyroidism or High-Normal TSH Levels.

Antidepressant-Resistant Depression in Patients With Comorbid Subclinical Hypothyroidism or High-Normal TSH Levels.

The neurobiology of central sensitization

AbstractCentral sensitization refers to the amplification of pain by central nervous system mechanisms. Classically described as a consequence of ongoing nociceptive input, it is increasingly recognized that central sensitization also occurs independent of peripheral injury or inflammation. Features of central sensitization have been identified in nearly all chronic pain conditions, and it is considered the primary underlying cause of pain in conditions such as fibromyalgia. Central sensitization is characterized in these conditions by widespread pain and multisite hyperalgesia/allodynia. Co‐occurring symptoms include fatigue, mood and cognitive problems, sleep disturbances, and multisensory hypersensitivity. Individuals with central sensitization often report previous exposure to psychosocial or physical stressors, and a higher personal lifetime and family history of pain, with the latter findings supported by genetic studies. Neuroimaging studies of central sensitization show evidence of: changes in brain gray matter in pain processing regions; neurochemical imbalances; and altered resting brain‐network connectivity between pronociceptive and antinociceptive brain areas. Immune system abnormalities have also been demonstrated in individuals with central sensitization. The recognition of central sensitization, and whether it is being driven by ongoing nociceptive input or it is occurring in the absence of a peripheral driver, is critical for effective pain management.

Bacterial colonization, overgrowth, and superinfection in atopic dermatitis

Staphylococcus aureus infection is a major burden for individuals with moderate-to-severe atopic dermatitis and a known inducer of disease exacerbation. This increased susceptibility to staphylococcal infections has been attributed to abnormalities in the innate immune system of atopic dermatitis (AD) skin, including deficits in barrier proteins and lipids, and a muted response in generating antimicrobial peptides, all of which is further impaired by the activation of Th2 and Th22 immune pathways, which characterizes AD. Skewing of the immune response with a reduced Th1:Th2 ratio and increased adherence of bacteria to AD skin are also thought to contribute. Bacterial species diversity is reduced with flares, concomitant with increases in S. aureus and sometimes clinical infection, which has recently been linked to the finding that commensal bacteria produce anti–S. aureus factors that contribute to the endogenous response. S. aureus produces several virulence factors affecting the skin barrier and immune system, including promoting Th2 cell activation. Best practices for the management of staphylococcal infections include systemic antibiotics, initiation of antiseptics (particularly dilute bleach baths), and sometimes periodic intranasal mupirocin. Newer evidence suggests the possibility that treatment of the skin with commensal bacterial species could also reduce S. aureus growth and increase diversity.

Pulmonary epithelial barrier and immunological functions at birth and in early life - key determinants of the development of asthma? A description of the protocol for the Breathing Together study.

Background. Childhood asthma is a common complex condition whose aetiology is thought to involve gene-environment interactions in early life occurring at the airway epithelium, associated with immune dysmaturation. It is not clear if abnormal airway epithelium cell (AEC) and cellular immune system functions associated with asthma are primary or secondary. To explore this, we will (i) recruit a birth cohort and observe the evolution of respiratory symptoms; (ii) recruit children with and without asthma symptoms; and (iii) use existing data from children in established STELAR birth cohorts. Novel pathways identified in the birth cohort will be sought in the children with established disease. Our over-arching hypothesis is that epithelium function is abnormal at birth in babies who subsequently develop asthma and progression is driven by abnormal interactions between the epithelium, genetic factors, the developing immune system, and the microbiome in the first years of life. Methods. One thousand babies will be recruited and nasal AEC collected at 5-10 days after birth for culture. Transcriptomes in AEC and blood leukocytes and the upper airway microbiome will be determined in babies and again at one and three years of age. In a subset of 100 individuals, AEC transcriptomes and microbiomes will also be assessed at three and six months. Individuals will be assigned a wheeze category at age three years. In a cross sectional study, 300 asthmatic and healthy children aged 1 to 16 years will have nasal and bronchial AEC collected for culture and transcriptome analysis, leukocyte transcriptome analysis, and upper and lower airway microbiomes ascertained. Genetic variants associated with asthma symptoms will be confirmed in the STELAR cohorts. Conclusions. This study is the first to comprehensively study the temporal relationship between aberrant AEC and immune cell function and asthma symptoms in the context of early gene-microbiome interactions.

Tu1822 - The Gut Microbiota of Pregnant Women with Crohn's Disease and their Babies is Associated with Abnormalities in the Adaptive Immune System - Results from the Meconium Study

Tu1822 - The Gut Microbiota of Pregnant Women with Crohn's Disease and their Babies is Associated with Abnormalities in the Adaptive Immune System - Results from the Meconium Study