HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy.

BACKGROUND: Food allergy is a growing health problem worldwide because of its increasing prevalence, life-threatening potential, and shortage of effective preventive treatments. In an outbreak of wheat allergy in Japan, thousands of patients had allergic reactions to wheat after using soap containing hydrolyzed wheat protein (HWP). OBJECTIVES: The aim of the present study was to investigate genetic variation that can contribute to susceptibility to HWP allergy. METHODS: We conducted a genome-wide association study of HWP allergy in 452 cases and 2700 control subjects using 6.6 million genotyped or imputed single nucleotide polymorphisms. Replication was assessed by genotyping single nucleotide polymorphisms in independent samples comprising 45 patients with HWP allergy and 326 control subjects. RESULTS: Through the genome-wide association study, we identified significant associations with the class II HLA region on 6p21 (P = 2.16 × 10-24 for rs9271588 and P = 2.96 × 10-24 for HLA-DQα1 amino acid position 34) and with the RBFOX1 locus at 16p13 (rs74575857, P = 8.4 × 10-9). The associations were also confirmed in the replication data set. Both amino acid polymorphisms (HLA-DQß1 amino acid positions 13 and 26) located in the P4 binding pockets on the HLA-DQ molecule achieved the genome-wide significance level (P < 5.0 × 10-8). CONCLUSIONS: Our data provide the first demonstration of genetic risk for HWP allergy and show that this genetic risk is mainly represented by multiple combinations of HLA variants.

Successful Treatment with Crushed Sofosbuvir/Velpatasvir of a Patient with Decompensated Cirrhosis C and Thrombocytopenia.

A 36-year-old woman with decompensated liver cirrhosis type C was referred to our hospital to receive antiviral treatment for hepatitis C virus (HCV). She had been diagnosed with intractable epilepsy and cerebral palsy at birth and was managed by central venous nutrition and nasal gastric feeding. At age 34 years, she was diagnosed with thrombocytopenia, probably associated with HCV infection. She showed refractory ascites for several months and was therefore administered crushed sofosbuvir/velpatasvir tablets via a nasal gastric tube. Her HCV infection was successfully eradicated, her ascites disappeared, and thrombocytopenia improved with a marked decrease in platelet-associated IgG.

Expansion of activated eosinophils in infants with severe atopic dermatitis.

BACKGROUND: There is increasing concern in Japan over infants with atopic dermatitis (AD) who present with severe systemic complications, such as hypoproteinemia, electrolyte disturbances, and delayed growth and development. They are often associated with extremely increased numbers of circulating eosinophils. However, the clinical significance of eosinophil expansion has not been thoroughly investigated. METHODS: This study attempted to determine the significance of eosinophilia and eosinophil activation in infant cases of AD by comparing multiple clinical parameters, indexes of eosinophil activation, and levels of serum cytokines. CD69 expression was determined by flow cytometry. The clinical severity of AD was graded by the severity SCORing of atopic dermatitis (SCORAD) method. Patients were classified into two groups, with and without CD69 on eosinophils. Nuclear lobes were evaluated under a microscopy. Serum levels of eosinophil-derived neurotoxin (EDN), interleukin (IL)-12, IL-18, IL-4, IL-5 and interferon (IFN)-gamma were determined by enzyme-linked immunosorbent assay. RESULTS: Patients with CD69-positive eosinophils had significantly higher numbers of eosinophils and platelets, total IgE, and eosinophil nuclear lobes. They also showed growth failure, developmental delay, low serum albumin, and electrolyte disturbances. EDN and IL-18 levels were significantly increased in this group, but the levels of IL-4, IL-5 and IL-12 were not significantly different between the two groups. IFN-gamma was not detectable in all patients with AD. Surface expression of CD69 indicates intense systemic allergic inflammation induced in severe cases of AD. CONCLUSIONS: Evaluation of eosinophil activation and early therapeutic intervention is mandatory for the treatment of severe AD during infancy.

Diagnostic value of serum EBV-DNA quantification and antibody to viral capsid antigen in nasopharyngeal carcinoma patients.

We compared the amount of serum Epstein-Barr virus DNA (EBV-DNA) detected in patients with nasopharyngeal carcinoma (NPC) in a high-incidence area, represented by Taiwan, and a low-incidence area, represented by Japan, using real-time quantitative PCR. The median serum EBV-DNA value in 41 Japanese NPC cases was 5450 copies/ml, and that in in 23 Taiwanese cases was 2125 copies/ml. The median serum EBV-DNA value in all 64 NPC cases was significantly higher than in control groups. Using receiver-operating-characteristic (ROC) curves, the sensitivity and specificity of EBV-DNA quantification were determined (cut-off point, 6.87 copies/ml; sensitivity, 0.855; specificity, 0.885) and compared with those of EBV-viral-capsid-antigen (VCA) titers; the results showed that EBV-DNA was a more sensitive and specific parameter than EBV-VCA titer. Then, we analyzed 19 NPC patients in whom recurrence developed (11 Japanese and 8 Taiwanese), and 26 NPC patients in continuous remission. Although there was no significant difference in EBV-DNA values between Japanese and Taiwanese patients, the value was significantly higher in the 19 patients with recurrence than in those in remission. ROC analysis again revealed a higher diagnostic value of EBV-DNA than EBV-VCA. These results suggest EBV-DNA is a more reliable tumor marker than EBV-VCA in both high-incidence and low-incidence areas of NPC.