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Dietary antibodies and gluten related seromarkers in children and young adults with cerebral palsy
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background & Aims: Cerebral palsy (CP), the most common physical disorder in children that affect motor function, is associated with a low weight and height. Celiac disease (CD), an autoimmune disorder precipitated by ingestion of gluten, is another common chronic disease in children that has a negative impact on growth. Based on our findings in a small pilot study, antibodies against gluten, dietary antigens and antibodies against transglutaminase 6(TG6) a new possible gluten related neurological marker have been investigated in an extended group of children with CP. The main aim of this thesis was to find out if the children with elevated gluten related antibodies have enteropathy consistent with CD and if they have antibodies to other dietary antigens as well. We further wanted to study if elevated levels of antibodies were associated to their weight, subtypes of CP and also to investigate if there were an association between the brain damage seen in CP and antibodies against TG6.

Methods: Ninety nine children with CP and matched (study4) controls (study3) were analysed for antibodies against gluten, TG6, egg white, lacto-globulin, casein and wheat. Small bowel biopsies were analysed in the majority of the children with antibody positivity, both by routine procedures and by extended analyse (study 2).

Results: Significantly elevated levels of gluten related seromarkers and antibodies against casein, lacto globulin and egg white were found in the CP-group compared to matched controls. The overall elevated levels of antibodies were more frequent in the tetraplegic (TP) and dyskinetic (DK) CP -subtypes having the most severe neurologic handicap and undernourishment. Routine and extended small bowel biopsies analysis did not indicate an increased prevalence of CD. Elevated antibodies against TG6 were found in the CP-group and significantly in the tetraplegic CP-subgroup.

Conclusion: Children with CP do not have increased prevalence of celiac disease but have elevated levels of gluten related seromarkers as well as antibodies against other dietary proteins compared to matched controls. There was a correlation between underweight, CP-subtypes (TP/DK) and occurrence of the tested antibodies suggesting disturbed intestinal permeability related to underweight. Compared to controls TG6 autoantibodies were found in the TP-subtype of CP that could be a result due to the brain damage.

Place, publisher, year, edition, pages
Örebro: Örebro universitet , 2012. , 97 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 72
Keyword [en]
Cerebral palsy, children, celiac disease, glutensensitivity, brain, transglutaminase 2 and 6, malnutrition, casein, eggwhite laktoglobulin
National Category
Medical and Health Sciences Pediatrics
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-24175ISBN: 978-91-7668-884-7 (print)OAI: oai:DiVA.org:oru-24175DiVA: diva2:542276
Public defence
2012-09-28, Wilandersalen, Universitetssjukhuset (USÖ), Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2012-07-31 Created: 2012-07-31 Last updated: 2016-04-25Bibliographically approved
List of papers
1. Increased prevalence of anti-gliadin antibodies and anti-tissue transglutaminase antibodies in children with cerebral palsy
Open this publication in new window or tab >>Increased prevalence of anti-gliadin antibodies and anti-tissue transglutaminase antibodies in children with cerebral palsy
2009 (English)In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 49, no 4, 424-429 p.Article in journal (Refereed) Published
Abstract [en]

AIM AND OBJECTIVE:: The aim of the study was to investigate whether there is any association between cerebral palsy (CP) and celiac disease (CD) in children.

PATIENTS AND METHODS:: Ninety children between 18 months and 18 years of age (median 9 years) with CP were included. Antibodies (IgA and IgG) against gliadin (AGA), endomysium (EMA), and tissue transglutaminase (tTG) were measured. Children with elevated levels of these antibodies were offered a small-bowel biopsy. RESULTS:: Thirty-nine children showed an elevated level of 1 or more of the tested antibodies (43%). None had raised EMA antibodies. Presence of tetraplegia or dyskinesia was associated with increased antibody levels (P = 0.045), as was a more severe functional type of CP (P = 0.008). Children with elevated antibodies had a lower body weight (P = 0.049), height (P = 0.041), and body mass index (BMI) (P = 0.014). Small-bowel biopsies were performed in 27 out of 39 children; 1 had CD and 2 had intraepithelial lymphocytosis.

CONCLUSIONS:: A large number of children with CP had elevated AGA and/or anti-tTG. Because these elevations were associated with lower weight, height, and BMI, it seemed of interest to speculate on how these findings correlated to CP and CD. However, we found no correlation between CP and CD.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2009
National Category
Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-8042 (URN)10.1097/MPG.0b013e31819a4e52 (DOI)000270473200009 ()19590452 (PubMedID)2-s2.0-70349731943 (Scopus ID)
Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2017-02-20Bibliographically approved
2. Early developing celiac disease in children with cerebral palsy
Open this publication in new window or tab >>Early developing celiac disease in children with cerebral palsy
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2011 (English)In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 53, no 6, 674-678 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: We have reported on increased levels of antibodies against gliadin and/or transglutaminase 2 (TG2) in children with cerebral palsy (CP) but without having increased prevalence of celiac disease (CD). The aim of the present study was to evaluate whether these children have mucosal signs of early developing CD, human leukocyte antigen (HLA)-DQ2/DQ8, and antibodies against deamidated gliadin peptides (DGP).

PATIENTS AND METHODS: Stored blood samples from 16 children with CP were analyzed regarding HLA-DQ2/DQ8 and anti-DGP antibodies. HLA-DQ2/DQ8 were analyzed by polymerase chain reaction sequence-specific oligonucleotide probes. Anti-DGP antibodies were analyzed with enzyme-linked immunosorbent assay. Small-bowel biopsies from 15 of these children were available for immunohistochemistry regarding IgA colocalized with TG2, densities of α/β+ and γ/δ+ intraepithelial lymphocytes.

RESULTS: Mucosal immunoglobulin A (IgA) deposits colocalized with TG2 were found in the small-bowel biopsy from 1 patient with serum IgA-class anti-TG2 antibodies, HLA-DQ2, and gastrointestinal complaints. Another 2 children had slightly increased numbers of mucosal α/β+ and/or γ/δ+ intraepithelial lymphocytes. In total, 10 of 16 children were HLA-DQ2 and/or DQ8-positive. Anti-DGP antibodies were detected in sera from 4 of 16 children.

CONCLUSIONS: In the present study, 1 child with CP had IgA colocalizing with TG2 in the small-bowel mucosa, suggesting CD at an early stage. Although the majority of children with CP and elevated levels of CD-related seromarkers are HLA-DQ2 and/or DQ8-positive, they have neither classical nor early developing CD.

National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-26570 (URN)10.1097/MPG.0b013e318229889d (DOI)21697743 (PubMedID)
Available from: 2012-12-03 Created: 2012-12-03 Last updated: 2012-12-03Bibliographically approved
3. Transglutaminase 6 antibodies in children and young adults with cerebral palsy
Open this publication in new window or tab >>Transglutaminase 6 antibodies in children and young adults with cerebral palsy
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(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-26571 (URN)
Available from: 2012-12-03 Created: 2012-12-03 Last updated: 2016-12-12Bibliographically approved
4. Increased prevalence of antibodies against dietary proteins in children and young adults with cerebral palsy
Open this publication in new window or tab >>Increased prevalence of antibodies against dietary proteins in children and young adults with cerebral palsy
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-26572 (URN)
Available from: 2012-12-03 Created: 2012-12-03 Last updated: 2016-12-12Bibliographically approved

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