Humoral Immune Response and Safety of SARS-CoV-2 Vaccination in Pediatric Inflammatory Bowel Disease

INTRODUCTION:Children with inflammatory bowel disease (IBD) may respond differently to COVID-19 immunization as compared with healthy children or adults with IBD. Those younger than 12 years receive a lower vaccine dose than adults. We sought to describe the safety and humoral immune response to COVID-19 vaccine in children with IBD.METHODS:We recruited children with IBD, ages 5-17 years, who received ≥ 2 doses of the BNT162b2 vaccine by a direct-to-patient outreach and at select sites. Patient demographics, IBD characteristics, medication use, and vaccine adverse events were collected. A subset of participants had quantitative measurement of anti-receptor binding domain IgG antibodies after 2-part immunization.RESULTS:Our study population included 280 participants. Only 1 participant required an ED visit or hospitalization because of an adverse event. Of 99 participants who underwent anti-receptor binding domain IgG antibody measurement, 98 had a detectable antibody, with a mean antibody level of 43.0 g/mL (SD 67) and a median of 22 g/mL (interquartile range 12-38). In adjusted analyses, older age (P = 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone (P = 0.005) were associated with a decreased antibody level. Antibody response in patients treated with antitumor necrosis factor combination vs monotherapy was numerically lower but not significant.DISCUSSION:Humoral immune response to COVID-19 immunization in children with IBD was robust, despite a high proportion of this pediatric cohort being treated with immunosuppressive agents. Severe vaccine-related AEs were rare. Overall, these findings provide a high level of reassurance that pediatric patients with IBD respond well and safely to SARS-CoV-2 vaccination

IBD Serology and Disease Outcomes in African Americans with Crohn's Disease

Backgrounds: Recent studies have identified the role of serologic markers in characterizing disease phenotype, location, complications, and severity among Northern Europeans (NE) with Crohn's disease (CD). However, very little is known about the role of serology in CD among African Americans (AA). Our study explored the relationship between serology and disease phenotype in AA with CD, while controlling for genetic ancestry. Methods: AAs with CD were enrolled as participants through multicenter collaborative efforts. Serological levels of IgA anti-Saccharomyces cervisiae antibody (ASCA), IgG ASCA, E. coli outermembrane porin C, anti-CBir1, and ANCA were measured using enzyme-linked immunosorbent assays. Genotyping was performed using Illumina immunochip technology; an admixture rate was calculated for each subject. Multiple imputation by chained equations was performed to account for data missing at random. Logistic regression was used to calculate adjusted odds ratio (OR) for associations between serological markers and both complicated disease and disease requiring surgery. Results: A total of 358 patients were included in the analysis. The majority of our patients had inflammatory, noncomplicated disease (58.4%), perianal disease (55.7%), and documented colonic inflammation (86.8%). On multivariable analysis, both IgG ASCA and OmpC were associated with complicated disease (OR, 2.67; 95% CI, 1.67-4.28; OR, 2.23; 95% CI, 1.41-3.53, respectively) and disease requiring surgery (OR, 2.51; 95% CI, 1.49-4.22; OR, 3.57; 95% CI, 2.12-6.00). NE admixture to the African genome did not have any associations or interactions in relation to clinical outcome. Conclusions: Our study comprises the largest cohort of AAs with CD. The utility of serological markers for the prognosis of CD in NE applies equally to AA populations

Desenvolvimento de um roteiro conceitual para a gestão da biodiversidade e dos serviços ecossistêmicos no Caribe mexicano

Coral reefs and mangroves support rich biodiversity and provide ecosystem services that range from food, recreational benefits and coastal protection services, among others. They are one of the most threatened ecosystems by urbanization processes. In this context, we developed a conceptual framework for the management of biodiversity and ecosystem services for these coastal environments. We based our workflow on two sections: “Information base” and “Governance” and use the Puerto Morelos Coastal region as a case study for coastal protection. Puerto Morelos is between two of the most touristic destinations of Mexico (Playa del Carmen and Cancun) that has experienced an increase of population in the past four decades resulting in an intensification of multiple threats to its ecosystems. We characterized the two ecosystems with a “Management Units” strategy. An expert-based ecosystem services matrix was also described in order to connect mangroves and coral reef ecosystems with the multiple beneficiaries. Then an ecosystem model (conceptual model and Global Biodiversity model) was developed. The conceptual model was useful in understanding the interplay processes between systems regarding the ecosystem service of “Coastal Protection”. The Global Biodiversity model evidenced the human-induced shifts in the biodiversity for mangrove and coral reefs ecosystems. Also, a projection for 2035 of “best” and “worst” scenarios was applied using GLOBIO3. A DPSIR conceptual framework was used to analyze environmental problems regarding ecosystem services maintenance. Finally, we evaluated a set of policies associated with these ecosystems that favor coastal protection integrity. This framework facilitates the identification of the most relevant processes and controls about the provision of coastal protection service. It can also be useful to better target management actions and as a tool to identify future management needs to tackle the challenges preventing more effective conservation of coastal environments.Recifes de coral e manguezais possuem rica biodiversidade e fornecem serviços ecossistêmicos, tais como, alimento, recreação, proteção costeira, entre outros. Esses ecossistemas encontram-se entre os mais ameaçados pelos processos de urbanização. Nesse contexto, desenvolvemos um roteiro conceitual para a gestão da biodiversidade e dos serviços ecossistêmicos desses ambientes costeiros. Organizamos nossa sequência de passos de trabalho em duas seções: “Base de informações” e “Governança” e usamos a região costeira da cidade de Puerto Morelos (México) como um estudo de caso para analisar o serviço de proteção de costa. Puerto Morelos encontra-se entre dois dos destinos mais turísticos do México (Playa del Carmen e Cancún), e portanto sua população vem aumentando nas últimas quatro décadas, resultando na intensificação de múltiplas ameaças para os ecossistemas. Primeiramente, caracterizamos os dois ecossistemas identificando-os como “Unidades de Gestão”, detalhando seus principais componentes e processos. Através de uma “Matriz de serviços ecossistêmicos”, construída com base na opinião de especialistas, foram sistematizados os principais serviços ecossistêmicos prestados pelos manguezais e recifes de corais aos múltiplos beneficiários. Em seguida, foi desenvolvida uma modelagem do sistema (e ecossistemas) através de sua representação na forma de um modelo conceitual e um modelo numérico de Biodiversidade Global. O modelo conceitual facilitou a compreensão dos processos de interação entre sistemas em relação ao serviço “Proteção Costeira”. O modelo numérico evidenciou as mudanças induzidas pelo homem na biodiversidade dos ecossistemas de manguezal e recifes de coral. Além disso, uma projeção dos cenários “melhor” e “pior” foi desenvolvida para 2035 usando GLOBIO3. A Estrutura conceitual DPSIR foi aplicada para analisar problemas ambientais relacionados à manutenção dos serviços ecossistêmicos. Finalmente, avaliamos um conjunto de políticas públicas associadas a esses ecossistemas e que favorecem a integridade da proteção costeira. Portanto, o roteiro facilitou a identificação dos principais processos e controles para a provisão de um serviço ecossistêmico. Além disso, pode ser útil para direcionar melhor as ações de gerenciamento, bem como, uma ferramenta para identificar necessidades futuras de planejamento e gestão para enfrentar desafios que permitam uma conservação mais eficaz dos ambientes costeiros.Fil: Sánchez Quinto, Andrés. Universidad Nacional Autónoma de México; MéxicoFil: Costa, Julliet Correa da. Universidade Federal de Santa Catarina; BrasilFil: Zamboni, Nadia Selene. Universidade Federal do Rio Grande do Norte; BrasilFil: Sanches, Fábio H. C.. Universidade Federal de Sao Paulo; BrasilFil: Principe, Silas C.. Universidade de Sao Paulo; BrasilFil: Viotto, Evangelina del Valle. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; ArgentinaFil: Casagranda, Maria Elvira. Universidad Nacional de Tucumán. Instituto de Ecología Regional. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Ecología Regional; ArgentinaFil: Lima, Francisco A. da Veiga. Universidade Federal de Santa Catarina; BrasilFil: Possamai, Bianca. Universidade Federal Do Rio Grande.; BrasilFil: Faroni Perez, Larisse. Universidade Federal de Juiz de Fora; Brasi

Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children

Background In contrast to pediatric Crohn's disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. Aim The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Methods Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Results Sixty-five percent of the patients had positive serology for pANCA, with 62% less than 12 years old and 66% 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ò100, found in 19%, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19% and more common in younger children with 32% less than 12 years old as compared with 14% 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). Conclusions The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age

Variation in care in the management of children with Crohn's disease: Data from a multicenter inception cohort study

Background: Variation in care is common in medical practice. Reducing variation in care is shown to improve quality and increase favorable outcomes in chronic diseases. We sought to identify factors associated with variation in care in children with newly diagnosed Crohn's disease (CD). Methods: Prospectively collected data from a 28-site multicenter inception CD cohort were analyzed for variations in diagnostic modalities, treatment, and follow-up monitoring practices, along with complicated disease outcomes over 3 years in 1046 children. Generalized linear mixed effects models were used to investigate the intercenter variations in each outcome variable. Results: The mean age at diagnosis was 12 years, and 25.9% were nonwhite. The number of participants ranged from 5 to 112 per site. No variation existed in the initial diagnostic approach. When medication exposure was analyzed, steroid exposure varied from 28.6% to 96.9% (P 0.99). Use of immunomodulators (IMs) varied among centers both within 90 days (P < 0.01) and during 3 years of follow-up (P < 0.01). A significant variation was seen at the geographic level with follow-up small bowel imaging and colonoscopy surveillance after initial therapy. Conclusions: Intercenter variation in care was seen with the initial use of steroids and anti-TNF, but there was no difference in total 3-year exposure to these drugs. Variation in the initiation and long-term use of IMs was significant among sites, but further research with objective measures is needed to explain this variation of care. Small bowel imaging or repeat colonoscopy in CD patients was not uniformly performed across sites. As our data show the widespread existence of variation in care and disease monitoring at geographic levels among pediatric CD patients, future implementation of various practice strategies may help reduce the variation in care

Management of Patients With Crohn's Disease and Ulcerative Colitis During the Coronavirus Disease-2019 Pandemic: Results of an International Meeting

The International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) is the only global organization devoted to the study of and management of the inflammatory bowel diseases (IBDs), namely, Crohn?s disease and ulcerative colitis. Membership is composed of physician-scientists who have established expertise in these diseases. The organization hosts an annual meeting and a number of working groups addressing issues of the epidemiology of IBD, diet and nutrition, and the development and use of treatments for IBD. There are currently 89 members of IOIBD representing 26 different countries. The organization has taken particular interest in the coronavirus disease-2019 (COVID-19) pandemic and how it may affect the IBD patient population. This document summarizes the results of 2 recent virtual meetings of the group and subsequent expert guidance for patients and providers

IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes.

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach