Abstract
Hashimoto's thyroiditis (HT) may occur associated with celiac disease (CD). Regulatory B cells (Breg) subsets have been shown to play a significant role in autoimmune processes. Therefore, we have characterized their distribution in the peripheral blood obtained from 10 patients with isolated HT, 10 patients with HT + CD, 9 patients with isolated CD, and 9 healthy donors (HD). Th17 cells were significantly increased in patients with HT and in patients bearing both HT and CD, while patients with isolated CD exhibited a lower percentage of Th17, as compared with healthy donors. CD24hiCD38hi Breg cells were significantly higher in patients with HT + CD and in patients with isolated CD as compared to both HD patients and patients with isolated HT (p = 0.0010). On the contrary, Breg memory phenotypes (CD24hiCD38− and CD24hiCD27+) significantly decreased in patients with HT + CD as compared with the isolated disorders. Following CpG oligodeoxynucleotide stimulation, IL-10+ CD24hiCD38hi Breg cells were similar in all groups of patients, despite these cells would have been higher in CD patients. In conclusion, celiac disease, isolated and even more when associated with HT, determines a peculiar behavior of Breg cells which are increased in number but possibly functionally defective. Furthermore, the association CD + HT was characterized by a reduction of Breg memory subsets as compared with the isolated disorders. The behavior of Th17 subset in patients with celiac disease associated with HT might have been sensitive to the effect of long-lasting GFD, and it is essentially determined by the presence of thyroid autoimmunity.
Highlights
Recent evidence has stressed that regulatory B (Breg) cells represent novel actors in maintaining the immune tolerance along with Th17 and regulatory T (Treg) cells [1, 2]
There was a significant increase of TH17 cells in patients with Hashimoto’s thyroiditis (HT) [12] even when it coexists with celiac disease (CD)
The percentage of nonstimulated CD24hiCD38hi Breg cells was increased in patients with CD even when associated with HT but not in patients with isolated HT, indicating that CD may enhance this regulatory response, as described for chronic intestinal inflammatory conditions by Mizoguchi et al [27]
Summary
Recent evidence has stressed that regulatory B (Breg) cells represent novel actors in maintaining the immune tolerance along with Th17 and regulatory T (Treg) cells [1, 2]. One of the most relevant is represented by celiac disease (CD) which has been described in a significant number of patients with Hashimoto’s thyroiditis (HT) [9, 10] as well as with other common autoimmune endocrine disorders [5, 10, 11]. The role of cellular immune response in the pathogenesis of these autoimmune disorders has been partially clarified [6,7,8]. As a matter of fact, in HT, a prevailing CD4+ Th1 polarization has been at first described [6, 7], but recently, it has been described an involvement of Th17 cells in its pathogenesis [12, 13]. Cellular immune response is relevant in CD pathogenesis: circulating Th17 cell levels were increased in adult patients, and they seemed to normalize upon appropriate gluten-free diet
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