We have identified a clinical association between self-reported non-celiac wheat sensitivity (NCWS) and Familial Mediterranean Fever (FMF). Objectives: A) To determine whether a 2-week double-blind placebo-controlled (DBPC) cross-over wheat vs. rice challenge exacerbates the clinical manifestations of FMF; B) to evaluate innate immune responses in NCWS/FMF patients challenged with wheat vs. rice. The study was conducted at the Department of Internal Medicine of the University Hospital of Palermo and the Hospital of Sciacca, Italy. Six female volunteers with FMF/NCWS (mean age 36 ± 6 years) were enrolled, 12 age-matched non-FMF, NCWS females, and 8 sex- and age-matched healthy subjects served as controls. We evaluated: 1. clinical symptoms by the FMF-specific AIDAI (Auto-Inflammatory Diseases Activity Index) score; 2. serum soluble CD14 (sCD14), C-reactive protein (CRP), and serum amyloid A (SSA); 3. circulating CD14⁺ monocytes expressing interleukin (IL)-1β and tumor necrosis factor (TNF)-α. The AIDAI score significantly increased in FMF patients during DBPC with wheat, but not with rice (19 ± 6.3 vs. 7 ± 1.6; p = 0.028). sCD14 values did not differ in FMF patients before and after the challenge, but were higher in FMF patients than in healthy controls (median values 11357 vs. 8710 pg/ml; p = 0.002). The percentage of circulating CD14⁺/IL-1β⁺ and of CD14⁺/TNF-α⁺ monocytes increased significantly after DBPC with wheat vs. baseline or rice challenge. Self-reported NCWS can hide an FMF diagnosis. Wheat ingestion exacerbated clinical and immunological features of FMF. Future studies performed on consecutive FMF patients recruited in centers for auto-inflammatory diseases will determine the real frequency and relevance of this association.

Primary Sjogren syndrome (pSS) is a complex autoimmune disease mainly affecting salivary and lacrimal glands. Several factors contribute to pSS pathogenesis; in particular, innate immunity seems to play a key role in disease etiology. Invariant natural killer (NK) T cells (iNKT) are a T-cell subset able to recognize glycolipid antigens. Their function remains unclear, but studies have pointed out their ability to modulate the immune system through the promotion of specific cytokine milieu. In this review, we discussed the possible role of iNKT in pSS development, as well as their implications as future markers of disease activity.

Fibromyalgia (FM) is a clinical syndrome characterized by chronic pain. FM patients complain hyperalgesia and allodynia and they are frequently affected by Non Celiac Wheat Sensitivity (NCWS), a condition where gastrointestinal and extraintestinal symptoms are triggered by gluten and/or wheat ingestion. The gluten-free diet (GFD) impact was evaluated on fibromyalgia-related and gastrointestinal symptoms, health-related quality of life and immune response of patients with both FM and NCWS in order to detect a possible pathogenetic role of wheat/gluten in the triggering of the inflammatory process. Peripheral blood from 8 FM patients, 10 FM and NCWS patients (FM+NCWS patients), 13 NCWS patients and 14 healthy subjects (HS) was taken before and after 8 weeks of GFD and used for cytofluorimetric analysis. In all FM+NCWS patients after GFD almost all the clinical parameters used to evaluate musculoskeletal and systemic symptoms related to FM were reduced as well as intestinal symptoms present before GFD. Moreover, pro-inflammatory cytokines production (IFN-γ, TNF- α, IL-17 and IL-22) by T helper (Th) cells of FM+NCWS patients was reduced after GFD. Our findings suggest that gluten/wheat could represent one of the triggering factors of the inflammatory condition playing an important role in the etiopathogenesis of both FM and NCWS.