Elevated levels of Celiac disease related antibodies in children with cerebral palsy

Background

We have previously reported increased occurrence of antibodies related to celiac disease (CD) in 39/90(43%) of children with cerebral palsy (CP) (ref.1). The children that were seropositive had a statistically significant lower weight, height and BMI and they were more severely handicapped. Small bowel routine biopsy showed that only one patient had flattened mucosa indicating CD and two had intraephitelial lymfocytosis. In this study we did a further investigation of the seropositive and biopsied children with CP to see if they have signs of early developing CD in small bowel mucosa

Purpose

To study immunomorphology in small bowel biopsies from children with Cerebral Palsy (CP) and elevated levels of celiac disease (CD) related antibodies despite normal routine mucosal histology. Genetic susceptibility for CD (HLA-DQ2 and 8) were analyzed.

Method

Immunomorphology including IgA colocalizations with tTG2 were analyzed in small bowel biopsies from 16 children with CP. HLA - typing was performed with PCR-SSOP.

Results

10/16 children (62%) were HLA-DQ2 and/or HLA-DQ8 positive.
15/16 biopsies were available for analyze. Elevated numbers of α/β+ and γ/d+ lymphocytes, positive staining for CD3 and DR3 as well as IgA co-localized with tTg2 was found in the mucosa from one child with elevated serum levels of IgA-antibodies against tissue transglutaminase. Slightly elevated numbers of mucosal α/β+ or gd+ lymphocytes and positive DR-staining without IgA-deposits were found in the biopsies from another two children. These three children were HLA DQ2 and/or HLA DQ8 positive and are diagnosed   “early developing CD”.
The biopsies from the 12 remaining children showed normal numbers of intraepithelial lymphocytes and no IgA-deposits were found. However, 7 of these showed slightly positive DR staining indicating an unspecific mucosal inflammation.
Routine histological analyses of small bowel biopsies may not be sufficient to identify CD at an early stage and analysis of immunomorphology including IgA colocalizations with tTG2 co-localization may prove useful when CD is suspected despite normal villous morphology.

Conclusion

Elevated levels of Celiac disease related antibodies in children with cerebral palsy(CD at an early stage and analysis of immunomorphology including IgA colocalizations with tTG2 co-localization may prove useful when CD is suspected despite normal villous morphology)
The majority of children with CP and elevated levels of CD-related seromarkers do not have classical CD, but rather an increased immune reactivity to gliadin.
Further studies are needed to evaluate if this ’gluten sensitivity’ has any impact on their nutritional problems or other clinical symptoms and if this reaction can be due to some extra intestinal manifestation from other organs in the body for example the brain?

Ref 1
Stenberg R, Dahle C, Lindberg E, Schollin J. Increased Prevalence of Anti-gliadin Antibodies and Anti-tissue Transglutaminase Antibodies in Children With Cerebral Palsy. J Pediatr Gastroenterol Nutr 2009.