To Örebro University

OBJECTIVE: Gastrointestinal problems are often seen in children with cerebral palsy, although the etiology and underlying mechanisms are not fully understood. Recent data point to significantly elevated levels of IgG antibody to dietary gluten in cerebral palsy independent of celiac disease, a gluten-mediated autoimmune enteropathy. We aimed to further characterize this antibody response by examining its subclass distribution and target reactivity in the context of relevant patient symptom profile.

METHODS: Study participants included children with cerebral palsy (n = 70) and celiac disease (n = 85), as well as unaffected controls (n = 30). Serum IgG antibody to gluten was investigated for subclass distribution, pattern of reactivity towards target proteins, and relationship with gastrointestinal symptoms and motor function.

RESULTS: The anti-gluten IgG antibody response in the cerebral palsy cohort was comprised of all four subclasses. However, in comparison with celiac disease, IgG1, IgG2, and IgG3 subclasses were significantly lower, whereas the IgG4 response was significantly higher in cerebral palsy. Within the cohort of cerebral palsy patients, levels of anti-gluten IgG1, IgG3, and IgG4 were greater in those with gastrointestinal symptoms, and the IgG3 subclass antibody correlated inversely with gross motor function. The anti-gluten IgG antibodies targeted a broad range of gliadin and glutenin proteins.

CONCLUSION: These findings reveal an anti-gluten IgG subclass distribution in cerebral palsy that is significantly different from that in celiac disease. Furthermore, the observed association between IgG subclass and symptom profile is suggestive of a relationship between the immune response and disease pathophysiology that may indicate a role for defects in gut immune and barrier function in cerebral palsy.

Objectives: We have previously reported a high prevalence of gluten-related serological markers (GRSM) in children and young adults with cerebral palsy (CP). The majority had no enteropathy to suggest coeliac disease (CD). Antibodies against transglutaminase 6 (anti-TG6) represent a new marker associated with gluten-related neurological dysfunction. The aim of this study was to investigate the prevalence of anti-TG6 antibodies in this group of individuals with an early neurological injury resulting in CP.

Materials and Methods: Sera from 96 patients with CP and 36 controls were analysed for IgA/IgG class anti-TG6 by ELISA.

Results: Anti-TG6 antibodies were found in 12/96 (13%) of patients with CP compared to 2/36 (6%) in controls. The tetraplegic subgroup of CP had a significantly higher prevalence of anti-TG6 antibodies 6/17 (35%) compared to the other subgroups and controls. There was no correlation of anti-TG6 autoantibodies with seropositivity to food proteins including gliadin.

Conclusions: An early brain insult and associated inflammation may predispose to future development of TG6 autoimmunity.

OBJECTIVES: Undernourishment is common in children with cerebral palsy (CP), but the reasons are unknown. We previously reported elevated levels of immunoglobulin (Ig) A and IgG antibodies against gliadin (AGA) and tissue transglutaminase (tTG) in 99 children and young adults with CP without characteristic findings of gluten enteropathy in small bowel biopsies. Our aim was to perform a case-control study of IgG antibodies against other dietary antigens, AGA, anti-tTG, and IgE antibodies against wheat and gluten.

METHODS: Sera from 99 cases with CP and 99 healthy, age- and sex-matched controls were analysed with fluorescence enzyme-linked immunosorbent assay for detection of IgG antibodies against β-lactoglobulin, casein, egg white, IgG- and IgA-AGA, IgA-anti-tTG, and IgE antibodies against gluten and wheat.

RESULTS: Compared with controls, the odds ratio in cases with CP for having elevated levels of IgG antibodies against β-lactoglobulin was 17.0 (95% confidence interval [CI] 2.3-128), against casein 11.0 (95% CI 2.6-46.8), and against egg white 7.0 (95% CI 1.6-30.8). The IgE responses for wheat/gluten were generally low. The tetraplegic and dyskinetic CP subtypes had significantly higher frequencies of elevated levels for all of the tested antibodies except IgG against egg white, and IgA-anti-tTG. A significantly lower weight was seen in cases with CP with positive versus negative serology.

CONCLUSIONS: Elevated levels of IgG against dietary antigens were more frequent in the CP group compared with controls, and particularly in the tetraplegic and dyskinetic CP subtypes with the most severe neurologic handicap and undernourishment. Hypothetically, malnourishment may cause increased intestinal permeability and thus immunization against dietary antigens.

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.

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.

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.

In nine children with severe cerebral palsy (CP), feeding difficulties and poor development of weight and height, laboratory markers for metabolic and enteral dysfunction were studied. CONCLUSION: Four of the nine patients with CP had increased levels of antigliadin antibodies AGA (IgA), a finding which calls for further studies concerning the possible connection between increased celiac markers and CP.