Serum antigliadin antibodies in cerebellar ataxias: a systematic review and meta-analysis

Abstract

Background: Gluten sensitivity refers to prominent immunological responses to gluten, usually in conjunction with elevated levels of serum antigliadin antibody (AGA). The association between AGA and cerebellar ataxias has been inconsistently reported.

Methods: We performed a systematic literature search and a meta-analysis to study the weighted pooled OR of idiopathic cerebellar ataxia (IDCA) cases to controls or to hereditary ataxia (HA) for AGA seropositivity using fixed effect model.

Results: Eleven studies were included, with a total of 847 IDCA cases, 1654 controls and 445 HA cases. IDCA cases had fourfold higher odds than controls (OR 4.28, 95% CI 3.10 to 5.90) and twofold higher odds than HA cases (OR 2.23, 95% CI 1.45 to 3.44) of having AGA seropositivity. Sensitivity analysis excluding the most weighted study, which accounted for 69% of the total weight, still showed similar associations (IDCA vs controls, OR 3.18, 95% CI 1.79 to 5.67 and IDCA vs HA, OR 1.72, 95% CI 1.03 to 2.86, respectively). The subgroup analysis showed that, when compared with controls, IDCA cases of both East Asian and Western countries had approximately threefold to fourfold higher odds to have AGA seropositivity (OR 3.41, 95% CI 1.67 to 6.97 and OR 4.53, 95% CI 3.16 to 6.49, respectively), suggesting the lack of ethnic heterogeneity. The odds of AGA seropositivity for HA cases was not significantly higher than controls (OR 1.41, 95% CI 0.82 to 2.44).

Conclusion: Our study indicates the association between AGA and IDCA, across different geographic regions.

Figure 1

Study selection flow diagram. ^aMEDLINE and Embase were searched via Ovid. Scopus was searched via Scopus.com. ^bHand search of citation lists from Google Scholar, selected studies and investigators further identified five additional published articles for review. Abstracts marked as yes or maybe on COVIDENCE by one or two reviewers were included in the full-text review. Different opinions between the two reviewers (C-YL and S-HK) in screening and eligibility were resolved by discussion and adjudication by a third, independent reviewer (WT). AGA, antigliadin antibody; CD, coeliac disease; DGP, deamidated gliadin peptide; TTG, tissue transglutaminase.

Figure 2

Pooled OR for antigliadin antibody seropositivity in idiopathic cerebellar ataxias vs controls (A) and idiopathic cerebellar ataxias vs hereditary ataxias (B) are represented by the diamonds. The grey solid squares indicate the OR of the individual study result. The size of the squares refers to the weight that each study contributes to the overall meta-analysis. The 95% CI for the individual and the pooled OR is specified.

Figure 3

Region-specific pooled OR for antigliadin antibody seropositivity in idiopathic cerebellar ataxias vs controls (A) and idiopathic cerebellar ataxias vs hereditary ataxias (B) are represented by the diamonds. The grey solid squares indicate the OR in individual study result. The size of the squares refers to the weight that each study contributes to the overall meta-analysis. The 95% CI for the individual and the pooled OR is specified.