Responses of peripheral blood mononucleated cells from non-celiac gluten sensitive patients to various cereal sources
Valerii et al. 2015
Over the last 60 years the prevalence of celiac disease (CD) has increased. Moreover, the increasing number of patients worldwide who are sensitive to dietary gluten but lack evidence of CD or wheat allergy has contributed to the identification of a new gluten-related syndrome known as non-celiac gluten sensitivity (NCGS). The molecular mechanisms of NCGS remain for the most part unknown, even if it is widely accepted that the innate immune system plays a major role in the onset of NCGS. Valerii et al. (2015) evaluated the in vitro chemokine response of peripheral blood mononucleated cells (PMBC) from NCGS patients to the wheat proteins of different cereals (including modern and ancient wheat genotypes) aiming to identify a possible marker for NCGS.
Results demonstrated that wheat protein induced an overactivation of the proinflammatory chemokine CXCL10 in PBMC from NCGS patients, and that the overactivation level depends on the cereal source from which proteins are obtained. The responses of PBMC from NCGS patients stimulated with protein extracts from flour containing gluten compared to stimulation with gluten-free flours (rice) showed a significantly higher level of secreted CXCL10 (P < 0.01) for all grains tested. This means that the secretion of CXCL10 is somehow stimulated by protein extracts of cereals containing gluten. Furthermore, CXCL10 is able to decrease the transepithelial resistance of monolayers of normal colonocytes (NCM 460) by diminishing the mRNA expression of cadherin-1 (CDH1) and tight junction protein 2 (TJP2), two primary components of the tight junction strands. When analysing separately the effect of the modern grains from that of the ancient grains, the authors found that modern dwarf varieties (Manitoba and Claudio) behave differently from the old varieties (SenatoreCappelli and Khorasan).
In conclusion, the results stress that wheat proteins trigger pro-inflammatory mechanisms in a manner dependent on the wheat variety, but independent of both gluten content and gluten allergenic epitopes, as they are currently known. In other words, it is reasonable to assume that other hitherto unknown pro-inflammatory characteristics of wheat proteins exist and are much more prominent in the protein extracts of modern dwarf varieties, if compared to ancient wheat genotypes. The results of this study show that CXCL10 overactivation is one of the mechanisms triggered by wheat proteins in PBMC obtained from NCGS patients.