Sage Journals: Discover world-class research

Abstract

Objectives

The aetiology of autism spectrum disorder (ASD) is multifactorial, sometimes genetic, and may be associated with abnormal immunological responses to peptides from proteins such as gluten. These peptides may cross the blood-brain barrier and affect neurotransmission, resulting in behavioural symptoms consistent with ASD. The aim of this study was to screen for markers of gluten-related immune reactivity in the absence of overt gastrointestinal symptoms in patients with ASD in the United Arab Emirates, a country associated with a high prevalence of ASD but lacking this type of research.

Methods

Patients diagnosed with ASD (using Diagnostic and Statistical Manual of Mental Disorders-IV-based criteria and Autism Diagnostic Observational Schedules) were compared with controls, regarding anti-tissue transglutaminase (tTG) immunoglobulin (Ig) A and anti-deamidated gliadin peptide (DGP) IgA levels.

Results

Sixty-six patients with ASD and 101 controls were included. Patients with ASD showed statistically significant lower anti-DGP IgA levels, but no significant difference in anti-tTG IgA levels, versus healthy controls. Correlations between immunological data and clinical symptoms were synergistic, but not statistically significant.

Conclusion

ASD may be associated with reduced levels of anti-DGP IgA.

Keywords

Autism spectrum disorders opioid excess theory gluten immunoglobulins neurotransmission anti-tissue transglutaminase antibody anti-gliadin antibody

Introduction

Autism spectrum disorder (ASD) is a group of conditions with an estimated prevalence up to around 1.5% in developed countries.^1–3 In children under 5 years of age, ASD is considered the leading cause of disability among all mental disorders, and the fourth in children aged 5–14 years.¹ The United Arab Emirates has been reported to have the highest estimated disability-adjusted-life-years rates for ASD compared with Western Europe (137/100 000 versus 99/100 000).¹ One of the challenges in ASD research is to identify plausible aetiological causes, particularly in view of the phenotypical heterogeneity of the disorder and the high rates of comorbidity.⁴

One theory postulates the contribution of the gut-brain axis to ASD, based on the observation that patients with ASD often experience a range of gastrointestinal disorders, including coeliac disease, food allergies, and other malabsorptions.^5,6 A proportion of biologically active peptides might cross the blood-brain barrier and interfere with the gut-brain axis.^6,7 In 1979, Panksepp suggested that peptides mimicking endogenous opiates may explain some ASD symptoms, such as decreased pain sensitivity, reduced desire for social contact and repetitive behaviours (e.g. self-injurious behaviour),⁸ which are ameliorated by naltrexone in a subgroup of patients.^9–11 More recently, gluten proteins originating from wheat have been implicated as main agents, passing through the intestine and the blood-brain barrier into the brain. Elevated levels of gluten exorphins have been found in the urine samples of patients with autism,¹² and may be an expression of increased gut permeability to these peptides. The theory implies a state of gluten immune response, defined as an enhanced immunologic reaction to gluten proteins.¹³ A 5-fold increased risk of altered serological tests specific for gluten related disorders, such as coeliac disease, has been reported in the early diagnosis of autism, even in the absence of inflammatory changes in the small intestine.¹⁴ Measurement of anti-tissue transglutaminase (tTG) and anti-deamidated gliadin peptide (DGP) immunoglobulins can provide a first line serological approach to identify coeliac disease,¹⁵ and individuals affected by non-coeliac gluten sensitivity may also test positive to raised levels of these immunoglobulins.¹⁶ To date, some studies have shown elevated anti-tTG and anti-DGP immunoglobulins in children with autistic disorders, while others have not.^17–20

The aim of the present study was to investigate gluten-related immune reactivity in a group of children diagnosed with ASD in the absence of gastrointestinal symptoms, in a part of the world where this type of research has not yet been conducted. This is of interest because epidemiological differences in ASD may also translate to gut-brain-axis activity.^21,22 Levels of anti-tTG and anti-DGP immunoglobulin (Ig) A were measured in children with ASD and compared with healthy children. To the best of the authors’ knowledge, this is the first study from the United Arab Emirates to investigate levels of markers of gluten-related immune reactivity in children with ASD. Higher levels of anti-tTG and anti-DGP IgAs in children with ASD, in the absence of gastrointestinal symptoms, was predicted to be suggestive of gluten sensitivity, and supportive of gut-brain-axis abnormalities in the aetiology of ASD.

Patients and methods

Study population and procedures

This case–control study was conducted at Al Ain Hospital, a major regional hospital in the Abu Dhabi region linked with the United Arab Emirates University (UAEU), College of Medicine and Health Sciences, Department of Psychiatry. The study followed ‘Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)’ guidelines (https: //www.equator-network.org/reporting-guidelines/strobe/). All male and female patients aged ≤16 years, referred to the Child Psychiatry Clinic at Al-Ain Hospital (Emirate of Abu Dhabi, UAE) with a confirmed diagnosis of ASD, were consecutively recruited between January 2013 and January 2016. Control subjects were recruited from randomly selected healthy siblings of children visiting the outpatient clinic for conditions other than ASD. To confirm diagnosis, children with suspected ASD were administered the Autism Diagnostic Observational Schedules (ADOS), a semi-structured tool for assessing individuals with suspected autism or other pervasive developmental disorders.²³ Patients were included if they met the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for ASD, and if they were free from any co-morbid DSM-IV Axis I condition and did not experience any gastrointestinal tract disorder according to their medical records. Participants were excluded from the study if they were aged >16 years, and/or if they were diagnosed with any physical conditions, or received any treatment that may affect the response of the immune system, or if they were receiving any special diet. Ethics approval for the study was obtained from the institutional review board at Al Ain Hospital, Al Ain City, Abu Dhabi, United Arab Emirates, in accordance with the Declaration of Helsinki (2000) (REC number: AAHEC-12-15-034, 27/01/2016). Written informed consent was obtained from the parents of all study participants.

All participants underwent a clinical assessment, conducted between 08.00 h and 11.00 h. Venous blood samples (5 ml) were collected and allowed to clot at room temperature for 30 min for serum preparation. Immediately following clinical assessment, serum samples were assessed for IgAs against tTG and DGP using relevant commercial enzyme-linked immunosorbent assays (Orgentec Diagnostica, Mainz, Germany) as per the manufacturer’s instructions. Absorbances of resultant colour reactions were determined at 450 nm (with a reference reading at 620 nm), and converted to IgA values in U/ml. Values greater than 15 U/ml (tTG) and 12 U/ml (DGP) were considered positive, as established by the manufacturer.

Statistical Analyses

Data are presented as mean ± SD, and were analysed using IBM SPSS software for Windows, version 25.0 (IBM, Armonk, NY, USA). Between-group differences in demographic and clinical data were analysed using χ²-test and independent-samples t-test. Biochemical and clinical data were assessed for normality and Log transformed as necessary. Multivariate analysis of covariance within the General Linear Model in SPSS was used to compare case versus control serum antibodies, and to account for confounding variables. Pairwise differences (post-hoc analyses) were Bonferroni corrected for multiple comparisons. Relationships between ADOS scores and serum antibodies were explored using Pearson’s correlation coefficient. Statistical significance was set to ensure 95% confidence intervals, conferring 0.80 power and an alpha error of 0.05 (two-tailed P value ≤0.05).

Results

Demographic and clinical characteristics

A total of 167 participants were included in the study, comprising 66 paediatric patients with ASD, and 101 healthy controls. The sample of patients with ASD represented 100% of the children diagnosed with ASD for the duration of the study. Demographic and clinical variables are presented in Table 1. Age and sex differed between the two groups and were accounted for as confounders in the general linear model analyses.

Table 1.

Demographic and clinical characteristics of paediatric patients with autism spectrum disorder (ASD) and healthy controls (HC).

Characteristic	ASDn = 66	HCn = 101	Statistical significance
Age, years	3.8 ± 1.3	4.1 ± 1.6	P < 0.001
Sex, male/female	53/13	60/41	P < 0.005
UAE native/non-native	35/31	60/41	P = 0.4
Anti-tTG IgA, U/ml	1.22 ± 2.15	0.95 ± 0.88	P = 0.32^a
Anti-DGP IgA, U/ml	2.79 ± 3.1	3.85 ± 4.43	P = 0.006^a

Data presented as mean ± SD or n prevalence.

UAE, United Arab Emirates; IgA, immunoglobulin A; tTG, tissue transglutaminase; DGP, deamidated gliadin peptide.

^aBetween-group effects with Bonferroni correction following multivariate analyses (P = 0.011) controlling for age and sex.

Anti-tissue transglutaminase IgA and anti-deamidated gliadin peptide IgA

Assays of serum IgA levels (U/ml) showed higher mean levels of anti-tTG and lower mean levels of anti-DGP in patients with ASD versus healthy controls (Table 1 and Figure 1). Multivariate analyses, after controlling for age and sex, indicated a statistically significant difference at group level (F = [2, 162] = 4.68, P = 0.011). Between-group analyses with Bonferroni correction indicated that this difference was driven by anti-DGP IgA levels reaching statistical significance (P = 0.006), whilst differences in anti-tTG IgA levels did not reach statistical significance (P = 0.32). No participant from either group showed clinically abnormal anti-tTG IgA levels (>15 U/ml). Two patients with ASD (3.0%) and five heathy control participants (5.0%) displayed anti-DGP IgA levels above the cut-off value (>12 U/ml).

Figure 1.

Levels of serum anti-tissue transglutaminase (tTG) immunoglobulin (Ig)A and anti-deamidated gliadin peptide (DGP) IgA in patients aged ≤ 16 years with autism spectrum disorder (ASD) and healthy controls (HC). Data presented as mean ± SE; *statistically significant difference (P = 0.006).

Correlation analyses

No statistically significant correlation was found between ADOS scores and levels of anti-DGP IgA (r = –0.065, P = 0.62) or levels of anti-tTG IgA (r = 0.014, P = 0.91). In addition, there was no statistically significant correlation between levels of anti-DGP and anti-tTG IgA (r = 0.093, P = 0.23).

Discussion

The aim of the present study was to screen for serological markers of gluten-related immune reactivity in a group of children with ASD in the absence of overt gastrointestinal symptoms compared with healthy individuals. To the best of the authors’ knowledge, this is the first such investigation carried out in the United Arab Emirates. The analyses indicated statistically significant lower anti-DGP IgA in children with ASD versus healthy children. Differences in anti-tTG IgA levels were not statistically significant between the two groups. In addition, there were no statistically significant correlations between ant-tTG and anti-DGP IgA levels, or between IgA levels and ADOS scores, although the direction of signal was inverse for anti-DGP IgA and positive for anti-tTG IgA in relation to ADOS scores.

Published evidence supports the role of the brain-gut axis in ASD, based on the frequent occurrence of gastrointestinal symptoms in children with autism (up to 70%) compared with children on a typical developmental trajectory (28%).^24–26 A number of case reports from the late sixties onwards introduced the possibility that a heightened immune response to gluten might contribute to ASD presentations.^27–32 In the general population, coeliac disease has a prevalence of approximately 1%,¹⁵ and is associated with genes coding for human leukocyte antigens (HLA) DQ2 and DQ8,^33,34 and immune responses to deamidated epitopes of gliadin and tTG.³⁵ In the presence of gastrointestinal symptoms and in the absence of criteria for coeliac disease or evidence of allergy, the condition is termed nonceliac gluten sensitivity,³⁶ which lacks objective diagnostic tests.^36–38 People with nonceliac gluten sensitivity can, however, test positive for anti-DGP IgG.¹⁶ The prevalence of nonceliac gluten sensitivity in the general population is known to range between 0.5% and 13%, which on average, is around 6 times higher than coeliac disease.³⁹

Findings from the present study do not support immunological hyperactivity in children with ASD compared with healthy children. Although various studies report positive results, some investigations have not found a significant association between ASD and elevated IgA levels. For example, Pavone et al (1997),¹⁹ found no elevated anti-gliadin levels in 11 patients with ASD. Out of 147 patients with ASD reported in another study, only one (0.68%) had abnormal anti-transglutaminase IgA levels and five (3.4%) had abnormal anti-gliadin IgA levels.¹⁷ Furthermore, anti-transglutaminase IgA levels in a sample of 162 children with ASD and 44 healthy controls were not found to reach the threshold for clinical abnormality in either group.¹⁸ The study also demonstrated that the prevalence of abnormal anti-DGP IgA was similar between children with ASD and healthy children, with only three children with ASD (2.3%) having clinically abnormal anti-DGP IgA.¹⁸ Finally, Lau et al (2013),¹³ found no significant difference in anti-DGP IgA in patients with ASD and their unaffected siblings versus healthy controls.

There are also inconsistencies in the literature investigating the relationship between coeliac disease and autism.⁴⁰ For example, one study demonstrated that the prevalence of coeliac disease in patients with autism was similar to 2 034 local healthy children.¹⁷ Among the 147 patients with ASD, only six tested positive for anti-DGP IgA or transglutaminase antibodies, whilst all participants tested negative for endomysium antibodies. Additionally, in this sample, the prevalence of ASD was not significantly greater than the general population when coeliac disease was confirmed by biopsy.¹⁷ Another study demonstrated no strict correlation between coeliac serology and ultrastructural changes in pathology.¹⁹ Out of 120 patients with coeliac disease, the prevalence of ASD was not greater than expected in patients with coeliac disease, whereas patients positive for anti-DGP and endomysium antibodies had normal intestinal mucosa.¹⁹ Interestingly, a very large epidemiological study from Sweden established that, although there was no association between coeliac disease or inflammation and ASD, the risk of ASD was significantly higher in the case of normal mucosa in combination with a positive coeliac disease serology.¹⁴

Although the cross-sectional nature of the present work precludes any comment regarding the nature of the association between ASD and anti-DGP IgA, the study does not support nonceliac gluten sensitivity in the present sample of children with ASD, based on the serology utilized. It is possible that the slightly lower anti-DGP IgA measured in the present study may be driven by a gluten-free diet,⁴¹ as diet was not evaluated. However, the role of gluten and a gluten-free diet in individuals with ASD remains unclear,⁴² and some studies evaluating diets have methodological failings.⁴³ Nevertheless, children on these diets may potentially have less immune reactivity to gluten-containing food products, which might result in underrepresentation of patients with elevated gluten-related immunological markers, or favour lower than expected measurements.⁴⁴ Salivary IgA has been proposed as an alternative biomarker for research on the mucosal immune system, as it appears independent from diet, although the authors of this proposal did not specifically test for anti-DGP or anti-tTG IgAs.⁴⁵ It is possible that there may be subgroups of patients with ASD who have different phenotypical manifestations of immune system dysregulation. Children with ASD and enhanced immunological activation may be those with either overt gastrointestinal symptoms (excluded from the present study) or those not yet symptomatic but at risk of developing coeliac disease or nonceliac gluten sensitivity. In view of the frequent occurrence of gastrointestinal symptoms in children with ASD, it might be valuable to screen their HLA status as early as possible to help identify individuals who are non-symptomatic at the time of ASD diagnosis (as in the present clinical sample) but who are at risk of developing symptoms later in life. Other explanations for the immune system being involved in the aetiology of ASD include the possibility that immunological dysfunction may be genetically driven, resulting in antibodies against self (e.g. central nervous system proteins), may follow maternal immune activation, or may be the result of potentially inefficient immunological responses to external pathogens.^46,47

The results of the present study may be limited by several factors, including the lack of HLA genotyping of participants, and lack of dietary intake control, which might have influenced the results. Furthermore, as the analyses did not correct for potential differences in total IgA levels, and secretory IgAs were not measured, it is not possible to comment on this parameter. It would have been preferable to match the present sample for sex and age at baseline, and to have access to detailed information regarding ethnicity, however, the analyses controlled for age and sex, and an overly conservative approach was adopted, utilizing Bonferroni correction when setting the threshold for statistical significance. A power calculation could not be performed in the absence of clear epidemiological data on the occurrence of nonceliac gluten sensitivity in children with ASD. The present data do allow a power calculation to be performed in further studies, which should be useful to generate new hypotheses. Strengths of the present study include the relatively large study population, and the inclusion of a medication free, homogenous group of individuals with no psychiatric or physical comorbidity.

In conclusion, this is the first study from the United Arab Emirates to compare anti-tTG and anti-DGP IgAs in paediatric patients with ASD versus healthy controls. Statistically significantly lower anti-DGP IgA levels were shown in patients with ASD. Future studies investigating the coeliac status of individuals with ASD with or without gastrointestinal symptoms, using a preferentially longitudinal approach, might help clarify the relationship between the gut-brain axis and ASD in relation to gluten.

Footnotes

Acknowledgement

The authors would like to thank staff at Al Ain Hospital and at the United Arab Emirates University for their help and dedication. We are particularly indebted to the participants and their families for their trust in taking part in the study.

Declaration of conflict of interest

DA has received travel grants from Janssen-Cilag and Servier Laboratories, and sponsorship from Lundbeck. The other authors declare that there is no conflict of interest.

Funding

Intramural funds were available to support this research.

ORCID iD

Danilo Arnone

References

Baxter

Brugha

Erskine

, et al. The epidemiology and global burden of autism spectrum disorders. Psychol Med 2015; 45: 601–613.

Christensen

Baio

Van Naarden Braun

, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States 2012. MMWR Surveill Summ 2016; 65: 1–23.

Wingate

Mulvihill

Kirby

, et al. Prevalence of autism spectrum disorders-Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ 2012; 61: 1–19.

Comi

Zimmerman

Frye

, et al. Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. J Child Neurol 1999; 14: 388–394.

Lázaro

Pondé

Rodrigues

LEA.

Opioid peptides and gastrointestinal symptoms in autism spectrum disorders.

Braz J Psychiatry 2016; 38: 243–246.

Van Sadelhoff

JHJ

Perez Pardo

, et al. The gut-immune-brain axis in autism spectrum disorders; a focus on amino acids. Front Endocrinol (Lausanne) 2019; 10: 247.

Liu

Udenigwe

CC.

Role of food-derived opioid peptides in the central nervous and gastrointestinal systems.

J Food Biochem 2019; 43: e12629.

Panksepp

A neurochemical theory of autism. Trends Neurosci 1979; 2: 174–177.

Bouvard

Leboyer

Launay

, et al. Low-dose naltrexone effects on plasma chemistries and clinical symptoms in autism: a double-blind, placebo-controlled study. Psychiatry Res 1995; 58: 191–201.

10.

Kolmen

Feldman

Handen

, et al. Naltrexone in young autistic children: replication study and learning measures. J Am Acad Child Adolesc Psychiatry 1997; 36: 1570–1578.

11.

Panksepp

Lensing

Brief report: a synopsis of an open-trial of naltrexone treatment of autism with four children.

J Autism Dev Disord 1991; 21: 243–249.

12.

Bojović

Stanković

Kotur

, et al. Genetic predictors of celiac disease, lactose intolerance, and vitamin D function and presence of peptide morphins in urine of children with neurodevelopmental disorders. Nutr Neurosci 2019; 22: 40–50.

13.

Lau

Green

PHR

Taylor

, et al. Markers of celiac disease and gluten sensitivity in children with autism. PLoS One 2013; 8: e66155.

14.

Ludvigsson

Reichenberg

Hultman

, et al. A nationwide study of the association between celiac disease and the risk of autistic spectrum disorders. JAMA Psychiatry 2013; 70: 1224–1230.

15.

Caio

Volta

Sapone

, et al. Celiac disease: a comprehensive current review. BMC Med 2019; 17: 142.

16.

Hadjivassiliou

Williamson

Woodroofe

The immunology of gluten sensitivity: beyond the gut.

Trends Immunol 2004; 25: 578–582.

17.

Batista

Gandolfi

Nobrega

YKM

, et al. Autism spectrum disorder and celiac disease: no evidence for a link. Arq Neuropsiquiatr 2012; 70: 28–33.

18.

De Magistris

Picardi

Siniscalco

, et al. Antibodies against food antigens in patients with autistic spectrum disorders. Biomed Res Int 2013; 2013: 729349.

19.

Pavone

Fiumara

Bottaro

, et al. Autism and celiac disease: failure to validate the hypothesis that a link might exist. Biol Psychiatry 1997; 42: 72–75.

20.

Szaflarska-Popławska

The relationship of autism spectrum disorders and celiac disease and gluten-free diet. International Journal of Celiac Disease 2015; 3: 132–135.

21.

Keen

Reid

Arnone

Autism, ethnicity and maternal immigration.

Br J Psychiatry 2010; 196: 274–281.

22.

Leonard

Sapone

Catassi

, et al. Celiac disease and nonceliac gluten sensitivity: a review. JAMA 2017; 318: 647–656.

23.

Lord

Rutter

DiLavore

, et al. Autism diagnostic observation schedule (ADOS). Los Angeles: Western Psychological Services, 1999.

24.

Buie

Campbell

Fuchs

3rd , et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 2010; 125: S1–S18.

25.

Valicenti-McDermott

McVicar

Rapin

, et al. Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease. J Dev Behav Pediatr 2006; 27: S128–S136.

26.

Bushara

KO.

Neurologic presentation of celiac disease.

Gastroenterology 2005; 128: S92–S97.

27.

Braffet

No milk, no bread please. Autism Society of Indiana Quarterly 1994; 1: 7–9.

28.

Goodwin

TC.

In a dark mirror.

Ment Hyg 1969; 53: 550–563.

29.

Goodwin

Cowen

Goodwin

TC.

Malabsorption and cerebral dysfunction: a multivariate and comparative study of autistic children.

J Autism Child Schizophr 1971; 1: 48–62.

30.

Reichelt

Saelid

Lindback

, et al. Childhood autism: a complex disorder. Biol Psychiatry 1986; 21: 1279–1290.

31.

Rimland

Progress in research. In: 4th annual meeting of the National Society for Autistic Children, Flint, Michigan, USA, 22 June–24 June 1972, p21. Washington, DC: US Department of Health, Education and Welfare, Public Health Service, National Institute of Mental Health, 1973.

32.

Vojdani

Perlmutter

Differentiation between celiac disease, nonceliac gluten sensitivity, and their overlapping with Crohn's disease: a case series. Case Reports Immunol 2013; 2013: 248482.

33.

Qiao

Iversen

Ráki

, et al. The adaptive immune response in celiac disease. Semin Immunopathol 2012; 34: 523–540.

34.

Husby

Koletzko

Korponay-Szabó

, et al. European society for pediatric gastroenterology, hepatology, and nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012; 54: 136–160.

35.

Briani

Samaroo

Alaedini

Celiac disease: from gluten to autoimmunity.

Autoimmun Rev 2008; 7: 644–650.

36.

Buie

The relationship of autism and gluten.

Clin Ther 2013; 35: 578–583.

37.

Ludvigsson

Leffler

Bai

, et al. The Oslo definitions for coeliac disease and related terms. Gut 2013; 62: 43–52.

38.

Fasano

Sapone

Zevallos

, et al. Nonceliac gluten sensitivity. Gastroenterology 2015; 148: 1195–1204.

39.

Barbaro

Cremon

Stanghellini

, et al. Recent advances in understanding non-celiac gluten sensitivity. F1000Res 2018; 7: F1000 Faculty Rev-1631.

40.

Cascella

Kryszak

Bhatti

, et al. Prevalence of celiac disease and gluten sensitivity in the United States clinical antipsychotic trials of intervention effectiveness study population. Schizophr Bull 2011; 37: 94–100.

41.

Trudeau

Madden

Parnell

, et al. Dietary and supplement-based complementary and alternative medicine use in pediatric autism spectrum disorder. Nutrients 2019; 11: 1783.

42.

Whiteley

Shattock

Knivsberg

, et al. Gluten- and casein-free dietary intervention for autism spectrum conditions. Front Hum Neurosci 2013; 6: 344.

43.

Reissmann

Hauser

Makulska-Gertruda

, et al. Gluten-free and casein-free diets in the treatment of Autism. Functional Foods in Health and Disease 2014; 4: 349–361.

44.

Hopper

Hadjivassiliou

Hurlstone

, et al. What is the role of serologic testing in celiac disease? A prospective, biopsy-confirmed study with economic analysis. Clin Gastroenterol Hepatol 2008; 6: 314–320.

45.

Lim

Nambiar

Muhardi

, et al. Young children display diurnal patterns of salivary IgA and alpha-amylase expression which are independent of food intake and demographic factors. Biomed Res Int 2019; 2019: 3687416.

46.

Meltzer

Van De Water

The role of the immune system in autism spectrum disorder.

Neuropsychopharmacology 2017; 42: 284–298.

47.

Ashwood

Van De Water

A review of autism and the immune response.

Clin Dev Immunol 2004; 11: 165–174.

Measures of gluten-related reactivity in children with autism spectrum disorders in the absence of overt gastrointestinal symptoms: a pilot study from the United Arab Emirates

Abstract

Objectives

Methods

Results

Conclusion

Keywords

Introduction

Patients and methods

Study population and procedures

Statistical Analyses

Results

Demographic and clinical characteristics

Anti-tissue transglutaminase IgA and anti-deamidated gliadin peptide IgA

Correlation analyses

Discussion

Footnotes

Acknowledgement

Declaration of conflict of interest

Funding

ORCID iD

References