Prevalence of antigliadin antibodies in ataxia patients

Methods.

Between January 2001 and December 2002, 95 patients and 73 healthy controls who were matched for age and gender to the patient group (table) were recruited at the Departments of Neurology at the University of Bonn and St. Josef Hospital in Bochum.

Thirty-two patients met diagnostic criteria of sporadic adult-onset ataxia of unknown etiology: (1) progressive ataxia; (2) disease onset after the age of 20 years; (3) informative and negative family history (no similar disorders in first- and second-degree relatives; parents older than 50 years, or, if not alive, age at death of more than 50 years); (4) negative molecular genetic tests for Friedreich’s ataxia (FRDA), spinocerebellar ataxia type 1 (SCA-1), SCA2, SCA3, SCA6, SCA7, SCA8, and SCA-17; (5) no established symptomatic cause (no onset of ataxia in association with encephalitis, sepsis, hyperthermia or heat stroke; no subacute onset; no ischemia, hemorrhage, or tumor of the posterior fossa; no alcohol abuse; no chronic intake of anticonvulsant drugs; no other toxic causes; no malignancies; anti-Hu, -Ri, and -Yo negative; normal levels of vitamin B12 and E; normal thyroid function; VDRL negative; normal CSF studies); and (6) diagnostic criteria for possible or probable multiple system atrophy not fulfilled.6,7⇓ In addition, we included 63 patients suffering from inherited ataxia. These patients had a family history suggestive of autosomal recessive or autosomal dominant inheritance or were tested positive for FRDA, SCA-1, SCA2, SCA3, and SCA6.

All subjects gave informed consent. The study was approved by the Ethical Committee of the Medical Faculty at the University of Bonn.

Detection of antigliadin IgG and IgA antibodies in serum samples was performed using a cap’s enzyme immunometric assay (UniCap Gliadin IgG/IgA ImmunoCAP; Pharmacia Diagnostics, Freiburg, Germany) following the manufacturer’s instructions. Serum levels above 18 mg/l (IgG) and 3 mg/l (IgA) were considered positive. The lower detection limit was 2 mg/l (IgG) and 1 mg/l (IgA). Antiendomysium antibodies were detected using indirect immunofluorescence (Viro-Immun Labor Diagnostika, Oberursel, Germany).

Results.

Antigliadin or antiendomysium antibodies were detected in 12% of the entire study population. Antigliadin IgA antibodies were most frequent (8%) followed by antigliadin IgG antibodies (4%), whereas antiendomysium antibodies were found in only two probands, one control, and one patient with sporadic ataxia. Distal duodenal biopsy samples showed mucosal changes in keeping with celiac disease in both.

Positive antibody findings were more frequent in sporadic adult-onset ataxia of unknown etiology (19%) than in recessive ataxia (8%), dominant ataxia (15%), and controls (8%) (table). However, statistical comparison did not reveal significant differences between the groups (p > 0.05; df = 3; χ² test). Age at examination (52 ± 14 versus 50 ± 16 years) and disease duration (11 ± 11 versus 11 ± 8 years) was almost identical in antigliadin-positive and –negative subjects.

To see whether the study groups differed with respect to antibody subtypes we separately analyzed the frequency of antigliadin IgA and IgG antibodies. IgA antibodies were found in 13% of patients with sporadic ataxia and with dominant ataxia and were less frequent in controls (5%) and recessive ataxia (4%). Antigliadin IgG antibodies were most frequent in recessive ataxia (8%) followed by sporadic ataxia (6%), dominant ataxia (5%), and controls (1%) (table). Statistical comparison of the prevalence of IgA and IgG antibodies between the study groups did not show significant differences (p > 0.05; df = 3; χ² test).

Since we were unable to detect statistically significant differences of the prevalence of positive antibody findings between controls and patient groups, we defined four levels of antigliadin IgA antibody concentrations (<1 mg/l, 1–2 mg/l, 2–3 mg/l, > 3 mg/l). IgA antibodies were selected because they had the highest prevalence in the study population. The median level was identical in all groups (<1 mg/l), and statistical comparison did not reveal differences (p > 0.05; Kruskal-Wallis test).

To see whether there was an association of a genetically defined subtype of ataxia with antigliadin antibodies, we determined the frequency of positive antibody findings in FRDA, recessive ataxia other than FRDA, in the various SCA disorders, and in dominant ataxia unlinked to one of the tested SCA loci. We found antigliadin antibodies in all groups except SCA2, which included only two patients. The frequency ranged from 7 to 33% (table), and statistical comparison did not reveal significant differences (p > 0.05; df = 7; χ² test). Similarly, there were no significant differences of the frequency of antigliadin IgA and antigliadin IgG antibodies between these groups (p > 0.05; df = 7; χ² test).

Discussion.

Our prospective study determined and compared the frequency of antigliadin antibodies in patients with sporadic adult-onset ataxia of unknown etiology, autosomal recessive, and autosomal dominant ataxia. In contrast to earlier studies, this study included a large group of matched healthy controls.

Although we found a trend toward a higher prevalence of antigliadin antibodies in patients with sporadic adult-onset ataxia of unknown etiology and with dominant ataxia, the differences were not significant. Because it was recently suggested that antigliadin antibodies of IgG type are the best markers for neurologic manifestations of gluten sensitivity,8 we additionally looked at antigliadin antibody subtypes. Again, we were unable to find significant differences between the study groups. Further, the frequency of antibody-positive probands did not significantly differ between controls and genetically defined patient groups. We do not believe that our negative findings are due to an invalid or unreliable detection system because the frequency of antigliadin antibodies in the present group of sporadic ataxia patients (19%) was close to the prevalence that we previously found in a distinct group of sporadic ataxia patients using another immunometric assay (15%).6 In addition, the prevalence of antigliadin antibodies in our group of healthy controls (8%) was in the same range as that of a number of large population-based studies (4 to 10%).

Although we were unable to find a statistical association between antigliadin antibodies and ataxia disorders, we cannot rule out that the presence of antibodies nevertheless represents a weak risk factor for the development of ataxia and that even larger study populations would be required to demonstrate a significant association. On the basis of the present data, however, we do not feel that it is justified to recommend a gluten-free diet to ataxia patients with positive antigliadin antibody findings.