Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature

Background Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs. Case presentation A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone. Conclusions Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods

Identification of effector candidate genes of Rhizoctonia solani AG-1 IA expressed during infection in Brachypodium distachyon

Rhizoctonia solani is a necrotrophic phytopathogen belonging to basidiomycetes. It causes rice sheath blight which inflicts serious damage in rice production. The infection strategy of this pathogen remains unclear. We previously demonstrated that salicylic acid-induced immunity could block R. solani AG-1 IA infection in both rice and Brachypodium distachyon. R. solani may undergo biotrophic process using effector proteins to suppress host immunity before necrotrophic stage. To identify pathogen genes expressed at the early infection process, here we developed an inoculation method using B. distachyon which enables to sample an increased amount of semi-synchronous infection hyphae. Sixty-one R. solani secretory effector-like protein genes (RsSEPGs) were identified using in silico approach with the publicly available gene annotation of R. solani AG-1 IA genome and our RNA-sequencing results obtained from hyphae grown on agar medium. Expression of RsSEPGs was analyzed at 6, 10, 16, 24, and 32 h after inoculation by a quantitative reverse transcription-polymerase chain reaction and 52 genes could be detected at least on a single time point tested. Their expressions showed phase-specific patterns which were classified into 6 clusters. The 23 RsSEPGs in the cluster 1-3 and 29 RsSEPGs in the cluster 4-6 are expected to be involved in biotrophic and necrotrophic interactions, respectively

Genome sequence and rapid evolution of the rice pathogen Xanthomonas oryzae pv. oryzae PXO99A

Background: Xanthomonas oryzae pv. oryzae causes bacterial blight of rice (Oryza sativa L.), a major disease that constrains production of this staple crop in many parts of the world. We report here on the complete genome sequence of strain PXO99A and its comparison to two previously sequenced strains, KACC10331 and MAFF311018, which are highly similar to one another. Results: The PXO99 A genome is a single circular chromosome of 5,240,075 bp, considerably longer than the genomes of the other strains (4,941,439 bp and 4,940,217 bp, respectively), and it contains 5083 protein-coding genes, including 87 not found in KACC10331 or MAFF311018. PXO99A contains a greater number of virulence-associated transcription activator-like effector genes and has at least ten major chromosomal rearrangements relative to KACC10331 and MAFF311018. PXO99 A contains numerous copies of diverse insertion sequence elements, members of which are associated with 7 out of 10 of the major rearrangements. A rapidly-evolving CRISPR (clustered regularly interspersed short palindromic repeats) region contains evidence of dozens of phage infections unique to the PXO99A lineage. PXO99A also contains a unique, near-perfect tandem repeat of 212 kilobases close to the replication terminus. Conclusion: Our results provide striking evidence of genome plasticity and rapid evolution within Xanthomonas oryzae pv. oryzae. The comparisons point to sources of genomic variation and candidates for strain-specific adaptations of this pathogen that help to explain the extraordinary diversity of Xanthomonas oryzae pv. oryzae genotypes and races that have been isolated from around the world. © 2008 Salzberg et al; licensee BioMed Central Ltd

Effects on Promoter Activity of Base Substitutions in the cis-Acting Regulatory Element of HrpXo Regulons in Xanthomonas oryzae pv. oryzae

In Xanthomonas oryzae pv. oryzae, the causal agent of bacterial leaf blight of rice, HrpXo is known to be a transcriptional regulator for the hypersensitive response and pathogenicity (hrp) genes. Several HrpXo regulons are preceded by a consensus sequence (TTCGC-N(15)-TTCGC), called the plant-inducible promoter (PIP) box, which is required for expression of the gene that follows. Thus, the PIP box can be an effective marker for screening HrpXo regulons from the genome database. It is not known, however, whether mutations in the PIP box cause a complete loss of promoter activity. In this study, we introduced base substitutions at each of the consensus nucleotides in the PIP box of the hrpC operon in X. oryzae pv. oryzae, and the promoter activity was examined by using a β-glucuronidase (GUS) reporter gene. Although the GUS activity was generally reduced by base substitutions, several mutated PIP boxes conferred considerable promoter activity. In several cases, even imperfect PIP boxes with two base substitutions retained 20% of the promoter activity found in the nonsubstituted PIP box. We screened HrpXo regulon candidates with an imperfect PIP box obtained from the genome database of X. oryzae pv. oryzae and found that at least two genes preceded by an imperfect PIP box with two base substitutions were actually expressed in an HrpXo-dependent manner. These results indicate that a base substitution in the PIP box is quite permissible for HrpXo-dependent expression and suggest that X. oryzae pv. oryzae may possess more HrpXo regulons than expected