BACKGROUND: In 1998 secretin, a gastrointestinal hormone, was suggested as an effective treatment for autism spectrum disorders (ASD) based on anecdotal evidence. OBJECTIVES: To assess whether intravenous secretin improves the core features of ASD, other aspects of behaviour or function such as self-injurious behaviour, and the quality of life of affected individuals and their carers. We also assessed whether secretin causes harm. This is an updated version of our review of this topic originally published in 2005. SEARCH METHODS: We searched CENTRAL (2010 Issue 1), MEDLINE (1950 to January 2010) , EMBASE (1980 to 2010 Week 2), PsycINFO (1806 to 2010 Week 2), CINAHL (1938 to January 2010), ERIC (1966 to January 2010), Sociological Abstracts (1952 to January 2010). Sociofile and HealthStar were searched in March 2005 when this review was first published, but were not available for this update. Records were limited to studies published since 1998 as this is when secretin was first proposed as a possible treatment for ASD. We searched reference lists of trials and reviews; we also contacted experts and trialists to find unpublished studies. SELECTION CRITERIA: Randomised controlled trials of intravenous secretin compared to a placebo treatment in children or adults diagnosed with ASD, where at least one standardised outcome measure was reported. DATA COLLECTION AND ANALYSIS: Sixteen studies met the inclusion criteria but for two of these, conducted by Repligen, the only available multisite data were reported in press releases. All outcome data from the other 14 trials were continuous. Where trials used cross-over designs, we conducted analysis on results from the first treatment phase. Where mean change from baseline was reported, we used this in preference to post-treatment scores for meta-analyses or forest plots. Meta-analysis was able to be attempted for only one outcome (Childhood Autism Rating Scale). Insufficient data were available to conduct sensitivity or subgroup analyses to assess the impact of study quality, clinical differences in the intervention or clinically relevant differences between groups, such as age or presence of gastrointestinal symptoms. MAIN RESULTS: Over 900 children were recruited for the secretin trials. Twenty-five established standardised outcome measures were reported to assess core features of ASD, communication, behaviour, visuospatial skills, affect and adverse events. One standardised measure of global impression was also used. No more than four studies used any one outcome measure similarly. When duration from the start of the intervention to outcome assessment was known, outcomes were reported at between three and six weeks. Meta-analysis of data was not possible but there is now consistency of findings, with RCTs of the efficacy of secretin in autism not showing improvements for core features of ASD. AUTHORS' CONCLUSIONS: There is no evidence that single or multiple dose intravenous secretin is effective and as such currently it should not be recommended or administered as a treatment for ASD. Further experimental assessment of secretin's effectiveness for ASD can only be justified if there is new high-quality and replicated scientific evidence that either finds that secretin has a role in neurotransmission in a way that could benefit all children with ASD or identifies important subgroups of children with ASD who could benefit from secretin because of a proven link between the action of secretin and the known cause of their ASD, or the type of problems they are experiencing.

/pdf/intravenous-secretin-for-autism-spectrum-disorders-asd-2f1rdtzdqe.pdf

Intravenous secretin for autism spectrum disorders (ASD).

Structural and functional properties of membrane and secreted IgD.

https://www.gastrojournal.org/article/0016-5085(87)90251-4/pdf

Effect of cholecystokinin and of its antagonist, of atropine, and of food on the release of immunoglobulin A and immunoglobulin G specific antibodies in the rat intestine

The intestinal mucosa is densely packed with antibody-secreting B cells, the majority of which produce IgA. Mucosal antibodies have traditionally been thought of as neutralizing antibodies that exclude antigens, but they also function in antigen sampling, allowing for selective transcytosis of antigens from the intestinal lumen. IgE-mediated antigen uptake can facilitate the development of allergic reactions to foods, but emerging evidence indicates that IgG-mediated antigen uptake may also play an important role in the development of immune tolerance to foods, particularly in the neonate. This review will focus on the role of intestinal immunoglobulins in the development of clinical tolerance and allergy to food antigens.

Mucosal antibodies in the regulation of tolerance and allergy to foods

Immunoglobulin (Ig) E is the principal Ig involved in immediate hypersensitivities and chronic allergic diseases such as asthma Helminths are the most potent infectious agents known for their capacity to stimulate IgE production during the course of infection In rats, the nematode Trichinella spiralis typically elicits a strong parasite-specific IgE response during infection, and this IgE antibody has been shown to be protective against the parasite in passive transfer experiments The study reported here analyzed the fate of 125I-labeled myeloma IgE (1R162) in normal and T spiralis-infected rats after intravenous injection T spiralis infection induced a capacity for specific binding to the gut wall of 125I-IgE rather than 125I-IgG1, as well as the transport of IgE, but not IgG1, into the gut lumen Peak intestinal uptake and transport of 125I-IgE occurred during the first and second weeks after injection but was not elevated in the fourth week, that is, after intestinal adult worms had been expelled Neither 125I-IgE uptake in the gut wall nor transport to the lumen could be ascribed to tissue damage or vascular leakage Luminal transport occurred in the small intestine and not the liver, which only transports low molecular weight degraded 125I-IgE Calculations based on the amount of intact IgE in the lumen suggest that, in a 24-h period, up to 20% of injected 125I-IgE can be transported to the gut lumen during the peak transport period, between 6 and 14 d after infection The intestinal IgE binding and transport response can be adoptively transferred with T spiralis immune CD4+ OX22- (CD45RC-) lymphocytes, which are protective, but not the nonprotective sister population CD4+ OX22+ (CD45RC+) of lymphocytes isolated simultaneously from thoracic duct lymph of infected rats The intravenous infusion of recombinant rat interleukin 4 also elicited significant intestinal uptake of 125I-IgE We also present evidence for the presence of CD23 on rat intraepithelial lymphocytes These data provide evidence for a novel, inducible, intestine-specific IgE uptake and transport mechanism

/pdf/evidence-for-an-interleukin-4-inducible-immunoglobulin-e-4ohyj5dudg.pdf

Evidence for an interleukin 4-inducible immunoglobulin E uptake and transport mechanism in the intestine.

Duodenal fluid IgE was reported to be increased in food allergy and in inflammatory conditions of the bowel. We studied the presence and specificity of IgE and IgD antibodies against alpha-casein, beta-lactoglobulin A, alpha-lactalbumin, bovine serum albumin and soy bean agglutinin using an enzyme-linked immunoassay (ELISA). Thirteen children with various intestinal diseases and thirteen normal adult volunteers were examined. In resting duodenal fluids, 8/13 of the children had IgE and 5/13 had IgD, while only 1/13 of the adults showed detectable IgE and IgD. After pancreozymin, 4/6 of the children and 4/8 of the adults showed detectable IgE and IgD in their duodenal fluids. After secretin, the duodenal fluids from 1/8 of the children and 2/8 of the adults had detectable IgE, while 6/13 children and 1/10 of the adults had IgD. The results indicate an increase in duodenal contents of IgE and IgD antibodies specific to cow's milk and soy protein after pancreozymin. Since this mediator is normally released during digestion, it is suggested that IgE and IgD antibodies specific for food proteins, may be involved in the physiological processing of foods in the intestine. In infants and children with gastrointestinal disease, the incidence of IgE and IgD antibodies specific for milk and soy proteins is higher in basal and pancreozymin-stimulated duodenal fluid when compared with control adults.

P C Shah

Papers

IgE and IgD antibodies to cow milk and soy protein in duodenal fluid: effects of pancreozymin and secretin.