Depression symptoms increase the risk for initiation or switching to biologic therapy in pediatric inflammatory bowel disease patients in remission.

BACKGROUND AND AIMS: Anxiety and depression symptoms are common in IBD population, both adult and pediatric patients. Increased psychological distress might contribute to initiation and switching to biologic therapy in adult patients with IBD or other chronic inflammatory diseases. Aim of the present study are to evaluate anxiety and depression symptoms in IBD pediatric patients with disease remission and investigate their role in initiation or switching to biologic therapy. METHODS: We performed a retrospective analysis on IBD pediatric patients, assessing for anxiety (GAD-7) and depression (PHQ-9) symptoms. Demographic and disease characteristics were obtained from medical records. RESULTS: Eighty-six patients [31 (36%) females - mean age = 15.6 (SD = 2.8) years] were included. Patients scored above cut-off (> 10) on PHQ-9 and GAD-7 were 17 (19.7%) and 18 (20.9%), respectively. No differences were found between UC and CD patients. Baseline clinically relevant depression symptoms were significantly associated with the odds of initiating or switching to biologic therapy within 2 years [OR = 4.5 (1.4-14.3)], even after confounders adjustment [4.2 (1.2-14.9)]. Relationship was not significant with anxiety symptoms. CONCLUSION: Anxiety and depression symptoms is relatively common in pediatric IBD population, even with disease remission. Pediatric IBD patients with high depression symptoms are at increased risk of initiating or switching to biologic therapy. Mental health screening programs should be incorporated in routine clinical practice, especially for depression, regardless of disease activity and disease type. Early diagnosis and proper intervention for mental illness should be part of routine IBD management.

Potential mechanisms for the hypothesized link between sunshine, vitamin D, and food allergy in children.

Epidemiologic data suggest that the incidence of food allergy (FA) is increasing among children, yet a satisfactory model of its pathogenesis remains elusive. FA is the consequence of maladaptive immune responses to common and otherwise innocuous food antigens. Concurrent with the increase in FA is an epidemic of vitamin D deficiency (VDD) caused by several factors, especially decreased sunlight/UVB exposure. There is growing appreciation of the importance of the pleiotropic hormone vitamin D in the development of tolerance, immune system defenses, and epithelial barrier integrity. We propose a "multiple-hit" model in which VDD in a developmentally critical period increases susceptibility to colonization with abnormal intestinal microbial flora and gastrointestinal infections, contributing to abnormal intestinal barrier permeability and excess and inappropriate exposure of the immune system to dietary allergens. A compounding effect (and additional "hit") of VDD is the promotion of a pro-sensitization immune imbalance that might compromise immunologic tolerance and contribute to FA. We propose that early correction of VDD might promote mucosal immunity, healthy microbial ecology, and allergen tolerance and thereby blunt the FA epidemic in children.

Season of birth and food allergy in children.

BACKGROUND: The prevalence of food allergy is rising, and etiologic factors remain uncertain. Evidence implicates a role for vitamin D in the development of atopic diseases. Based on seasonal patterns of UV-B exposure (and consequent vitamin D status), we hypothesized that patients with food allergy are more often born in fall or winter. OBJECTIVE: To investigate whether season of birth is associated with food allergy. METHODS: We performed a multicenter medical record review of all patients presenting to 3 Boston emergency departments (EDs) for food-related acute allergic reactions between January 1, 2001, and December 31, 2006. Months of birth in patients with food allergy were compared with that of patients visiting the ED for reasons other than food allergy. RESULTS: We studied 1002 patients with food allergy. Of younger children with food allergy (age < 5 years), but not older children or adults, 41% were born in spring or summer compared with 59% in fall or winter (P = .002). This approximately 40:60 ratio differed from birth season in children treated in the ED for non-food allergy reasons (P = .002). Children younger than 5 years born in fall or winter had a 53% higher odds of food allergy compared with controls. This finding was independent of the suspected triggering food and allergic comorbidities. CONCLUSIONS: Food allergy is more common in Boston children born in the fall and winter seasons. We propose that these findings are mediated by seasonal differences in UV-B exposure. These results add support to the hypothesis that seasonal fluctuations in sunlight and perhaps vitamin D may be involved in the pathogenesis of food allergy.

Neonatal microbial flora and disease outcome.

The now outdated perception of microorganisms of the gastrointestinal tract as pathogens or at best commensals continues to undergo remodeling. It is now clear that the microbiome of the gut participates in many activities including: digestion, ecologic protection from pathogens, and an increasingly appreciated immunoregulatory role in vertebrates. Studies of the complex interactions of microbes and hosts point to a convergence of two well-supported (though imperfect) hypotheses: the 'hygiene hypothesis' and the 'fetal programming hypothesis' proposed by Strachan and Barker, respectively. Our current understanding is one in which factors that exist before conception, during gestation, or occur perinatally in the infant milieu, in addition to exposures to nutrients and microbes, have the potential for long-term effects in the development of healthy offsprings and adults. Epidemiology, basic science and clinical research in such previously diverse areas of study such as microbiology, allergy, gastroenterology, endocrinology, immunology, rheumatology, infectious disease, perinatology, and nutrition are providing evidence that appropriate development and tendency towards the development of certain diseases are directly affected by intestinal microbe-host interactions. It appears likely that perinatal colonization of the gastrointestinal tract is a particularly pivotal process in which microbe-host programming occurs. Intestinal microbes and hosts have co-evolved that, when in appropriate balance, they produce and propagate a life-long mutualism.

Isoform-specific interaction of HP1 with human TAFII130.

The general transcription factor TFIID facilitates recruitment of the transcription machinery to gene promoters and regulates initiation of transcription by RNA polymerase II. hTAF(II)130, a component of TFIID, interacts with and serves as a coactivator for multiple transcriptional regulatory proteins, including Sp1 and CREB. A yeast two-hybrid screen has identified an interaction between hTAF(II)130 and heterochromatin protein 1 (HP1), a chromatin-associated protein whose function has been implicated in gene silencing. We find that hTAF(II)130 associates with HP1 in an isoform-specific manner: HP1alpha and HP1gamma bind to hTAF(II)130, but not HP1beta. In addition, we show that endogenous hTAF(II)130 and components of TFIID in HeLa nuclear extracts associate with glutathione S-transferase-HP1alpha and -HP1gamma. hTAF(II)130 possesses a pentapeptide HP1-binding motif, and mutation of the hTAF(II)130 HP1 box compromises the interaction of hTAF(II)130 with HP1. We demonstrate that Gal4-HP1 proteins interfere with hTAF(II)130-mediated activation of transcription. Our results suggest that HP1alpha and HP1gamma associate with hTAF(II)130 to mediate repression of transcription, supporting a new model of transcriptional repression involving a specific interaction between a component of TFIID and chromatin.