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<title>Abstract</title> Systemic juvenile idiopathic arthritis (sJIA) is an autoinflammatory disease caused by high production of inflammatory cytokines. Conventional biomarkers, such as IL-18 are reportedly not always associated with frequent relapses or complication with macrophage activation syndrome (MAS). As few specific biomarkers that can indicate and evaluate the sJIA disease activity have been identified, the discovery of biomarkers is very important. We performed a deep proteomic analysis of serum samples from nine patients with sJIA using highly sensitive mass spectrometry, and identified differentially expressed proteins in various disease phases. We selected 68 proteins (URPs) that were highly expressed in the active phase from total of 2,727 proteins. Pathway analysis revealed that the URPs included proteins related to many immune process and proteasome proteins, which might be associated with the pathogenesis of sJIA. Based on these results, four proteins (leucine aminopeptidase 3; LAP3, guanylate-binding protein 1; GBP1, Heme oxygenase 1; HMOX1, and bone morphogenetic protein 10; BMP10), which exhibit high fold changes during the active phase or which might be core proteins in the functional network were selected as candidate biomarkers. These proteins may be clinically useful for diagnostic and therapeutic purposes and might help determine the pathogenesis of the disease.

[This corrects the article DOI: 10.1016/j.waojou.2019.100065.].

【背景・目的】牛乳アレルギー児に対する免疫療法や栄養食事指導では、しばしば嗜好の問題から継続摂取困難となる。対策として、本研究では嗜好調査とレシピ開発を行った。【方法】牛乳アレルギーの既往があり、現在は牛乳200mL程度を摂取可能となった児と保護者を対象とした。牛乳の摂取状況や嗜好を調査し、嗜好を考慮した乳成分含有メニューを考案し試食会にて評価した。非アレルギー児を対照群とし、一般小児における牛乳の嗜好も調査した。【結果】対象児49名(年齢中央値:10歳8ヵ月)中、46名は牛乳の免疫療法を経験していた。乳製品は牛乳より好まれ、牛乳が「嫌い」な児の牛乳摂取開始年齢は「好き」な児よりも有意に高かった(中央値:各8歳、5歳、p<0.05)。試食会では、児はかすかな牛乳・乳製品の味やにおいも敏感に感じ取り、摂取の妨げとなっていた。【まとめ】牛乳の摂取開始年齢は嗜好に影響し、早期の摂取開始が牛乳嫌いの回避に役立つ可能性が示唆された。調理の際は、牛乳・乳製品の味やにおいを低減する工夫等が重要である。(著者抄録)

Individuals with immunosuppressive condition have a high risk of invasive Haemophilus influenzae type b (Hib) infection. In Japan, routine Hib vaccination program for children under 5 years old was introduced in December 2008. However, the national policy does not make provision for individuals aged ≥5 years who have medical conditions associated with a high risk of invasive Hib disease to receive Hib vaccine. We measured serum anti-polyribosylribitol phosphate specific (anti-PRP) antibodies to Hib in patients aged ≥5 years with hematological malignancies and asplenia and evaluated their levels of anti-PRP antibodies in post administration of Hib vaccine era. A total of 65 patients (48 with hematological malignancies, and 17 with asplenia) were included in this study, of which 84% had not received Hib vaccine. In addition, 95.4% had short-term protective levels of anti-PRP antibodies (defined as ≥0.15 μg/mL) and 41.5% had long-term protective levels of anti-PRP antibodies (defined as ≥1.0 μg/mL). Five patients had low anti-PRP antibody levels despite a history of Hib vaccination. Our results suggest that young patients with underlying diseases such as hematological malignancies and asplenia may be at risk of invasive Hib disease. Hence, we recommend they should receive Hib vaccines even if they are over the age limit for routine Hib vaccination program.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is a neurocutaneous disease, characterized by tumorigenesis and developmental anomalies due to aberrant sonic hedgehog (Shh) signaling. Patients with NBCCS typically appear calm and carefree, suggesting that the specific personality in these patients may be associated with an enhanced hedgehog pathway. Our study aimed to determine the personality type in these patients. METHODS: We enrolled 14 mentally normal patients with genetically-confirmed NBCCS (7 males and 7 females; mean age = 25.2 years) and 20 controls (10 males and 10 females; mean age = 27.9 years). The patients were assessed with the Japanese version of the Temperament and Character Inventory, based on the seven-dimensional model of temperament and character, and their clinical symptoms were evaluated. The amygdala volumes of 6 patients with NBCCS were measured using magnetic resonance imaging with an image processing software. RESULTS: Patients with NBCCS scored significantly lower on harm avoidance (0.89) than controls (1.00; p = 0.0084). Moreover, patients with NBCCS having developmental malformations such as rib anomalies, who may have experienced Shh signaling enhancement from the prenatal period, scored significantly lower on harm avoidance (0.80 [p = 0.0031]). The left amygdala volume was also significantly reduced in patients with NBCCS (p = 0.0426). CONCLUSIONS: Patients with NBCCS who experienced increased Shh signaling from the prenatal period showed significantly lower harm avoidance relate to serotonin. The left amygdala volume was significantly reduced in these patients. Our results indicate that Shh signaling may influence the human personality.

Atopic dermatitis (AD) is commonly associated with colonization by <italic>Staphylococcus aureus</italic> in the affected skin. To understand the role of <italic>S. aureus</italic> in the development of AD, we performed whole-genome sequencing of <italic>S. aureus</italic> strains isolated from the cheek skin of 268 Japanese infants 1 and 6 months after birth. About 45% of infants were colonized with <italic>S. aureus</italic> at 1 month regardless of AD outcome. In contrast, skin colonization by <italic>S. aureus</italic> at 6 months of age increased the risk of developing AD. Acquisition of dysfunctional mutations in the <italic>S. aureus</italic> Agr quorum-sensing (QS) system was primarily observed in strains from 6-month-old infants who did not develop AD. Expression of a functional Agr system in <italic>S. aureus</italic> was required for epidermal colonization and the induction of AD-like inflammation in mice. Thus, retention of functional <italic>S. aureus agr</italic> virulence during infancy is associated with pathogen skin colonization and the development of AD.

Although some probiotic bacteria have been reported to prevent infections in children, there are few well-designed double-blind studies. Here we evaluated the effects of a probiotic strain of lactic acid bacteria (LAB), Pediococcus acidilactici K15, on viral respiratory tract infections in preschool children. A four-month, randomized, double-blind, placebo-controlled study was performed in 172 healthy children aged 3 to 6 years. Subjects were administered dextrin alone or dextrin including heat-killed K15 (5 × 1010 bacteria). The number of febrile days was the primary outcome. The number of absent days from preschools and the influenza incidence were secondary outcomes. Secretory IgA (sIgA) concentrations in saliva were measured as an exploratory outcome. The primary and secondary outcomes were not significantly different between both groups. Analyses in children with little intake of fermented foods including LAB showed that the duration of a fever significantly decreased by K15 intake. The salivary sIgA level in the K15 group was maintained significantly higher than it was in the placebo group. The effects of K15 on preventing viral respiratory tract infections were not observed without the restriction of fermented foods intake. However, K15 supported anti-infectious immune systems in children who took less fermented foods and the maintenance of salivary sIgA levels in all subjects.

Pathogenic germline variants in the gap junction protein alpha 1 (GJA1) gene have been identified in several congenital disorders affecting cutaneous, skeletal, and cardiac tissues. Here, we describe a 12-year-old patient with a GJA1 c.113G>A, p.(Gly38Glu) variant, who presented with fulminant myocarditis following recurrent generalized erythrokeratoderma. His mother and younger sister had the same clinical manifestations with the same GJA1 variant, but did not have cardiac dysfunction. GJA1 variants have been reported in patients with congenital cardiac malformations, while acute myocarditis in GJA1-related disorders has not been reported so far.

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.