Identification of a single nucleotide deletion in the novel HLA-DQB1*06:379N allele, detected by Polymerase Chain Reaction-Sequence Based Typing but not by Next Generation Sequencing.

In this report we describe the characterization of a novel null HLA-DQB1 allele, detected by polymerase chain reaction-sequence-based typing but not by next-generation sequencing (NGS). The new allele, HLA-DQB1*06:379N, was discovered in an Italian patient with acute myeloid leukemia and also in one of her healthy siblings. The new allele is largely homologous to DQB1*06:02:01:01 with a T deletion in exon 2, in codon 11, which causes a frameshift and the formation of an unusual and premature TGA STOP in codon 27. This case report underlines the importance of not removing Sanger method sequencing from routine use for high-resolution HLA typing, but to maintain it together with NGS technology.

Wheat Consumption Leads to Immune Activation and Symptom Worsening in Patients with Familial Mediterranean Fever: A Pilot Randomized Trial.

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)-1ß 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-1ß+ 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.