Autoimmune diseases and celiac disease which came first: genotype or gluten?

Abstract

Celiac disease (CD) is associated with several autoimmune diseases (ADs) and, in particular, thyroid autoimmunity (TA) and Type 1 diabetes (T1D). TA and T1D are defined as ‘associated conditions’ to CD (conditions at increased prevalence in CD but not directly related to gluten ingestion). The diagnosis of CD may precede or follow that of TA/T1D. To date, the available evidence suggests that the common genetic background is the main factor determining the high prevalence of the association. Conversely, no conclusive findings clarify whether extrinsic gluten-related factors (age at the first introduction, concomitant breastfeeding, length of gluten exposure and gluten-free diet) may link CD to the ADs. The aim of this review is to evaluate whether genetic background alone could explain the association between CD and ADs or if gluten-related factors ought to be considered. The pathophysiological links clarifying how the gluten-related factors could predispose to ADs will also be discussed.

Keywords:

• adolescent
• autoimmune diseases
• celiac disease
• child
• thyroid autoimmunity
• type 1 diabetes

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• About 30% of all the patients with CD have one or more ADs, while in the general population, ADs have a prevalence ranging from 3 to 9.4%. The nature of the link between CD and ADs has not been completely identified yet. A higher prevalence of ADs in relatives of CD subjects suggests genetic background as the main factor.

• Gluten is involved in changes of gut permeability and intestinal microbiota, in molecular mimicry between wheat and human proteins and in activation of T-cell mediated. All these mechanisms make it a potential trigger for ADs.

• T1D and TA can be considered as a model of ADs due to their high co-occurrence in CD.

• Weak evidence supports the assumption that the first introduction of gluten between 4 and 6 months could be advantageous to reduce the risk of ADs development.

• Breastfeeding length does not prevent the risk of developing ADs, while the first gluten introduction during breastfeeding may be considered a protective measure.

• The length of gluten exposure before CD diagnosis in several surveys does not impact the future development of T1D and TA.

• The recent clinical advances highlight that GFD does not prevent the occurrence of ADs.

• Anecdotal cases showed that GFD may impact the outcome of ADs clinical course, but it needs to be confirmed by future clinical trials.

• The compliance with GFD may probably have no impact on the risk of developing ADs, as we can argue based on previous findings, although this aspect has not been specifically addressed in this review.