Language：Japanese   Publisher：(一社)日本小児栄養消化器肝臓学会  

Language：English   Publisher：(一社)日本小児血液・がん学会  

Language：Japanese   Publisher：Pediatrics International  

DOI： 10.1111/ped.70206

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PubMed

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：Japanese   Publisher：Frontiers in Immunology  

Background: GATA2 deficiency, a syndrome caused by heterozygous loss-of-function variants in the GATA2 gene, is characterized by immunodeficiency, bone marrow failure, and predisposition to myeloid neoplasms. Its clinical presentation is highly variable, making early diagnosis challenging. Although GATA2 deficiency has been linked to systemic inflammation, gastrointestinal involvement mimicking inflammatory bowel disease (IBD) is extremely rare. Case presentation: This report presented the case of two adolescent boys with no family history of novel heterozygous frameshift GATA2 variants. Notably, Patient 1 initially presented with clinical and endoscopic features strongly suggestive of Crohn’s disease, including weight loss, perianal abscess, and characteristic intestinal ulcers, before developing acute myeloid leukemia with monosomy 7. This is a rare presentation of GATA2 deficiency manifesting initially with Crohn’s disease-like symptoms. Patient 2 presented with intractable cutaneous warts and pancytopenia, later diagnosed as myelodysplastic syndrome with der(1;7)(q10;p10). Both patients harbored novel GATA2 frameshift variants predicted to eliminate the DNA-binding domain, suggesting a loss-of-function mechanism. Conclusion: These cases expand the phenotypic spectrum of GATA2 deficiency and highlight that atypical IBD-like symptoms, including Crohn’s disease-like presentations, may cause an initial manifestation. GATA2 deficiency should be considered in patients with IBD-like symptoms, refractory skin disorders, and hematological abnormalities. Early genetic testing and family screening are essential to ensuring timely diagnosis and curative hematopoietic stem cell transplantation before progression to advanced myeloid disease.

DOI： 10.3389/fimmu.2025.1644552

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PubMed

Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

Language：Japanese   Publisher：(公社)日本小児科学会  

Language：Japanese   Publisher：(公社)日本小児科学会  

Language：Japanese   Publisher：(一社)日本リウマチ学会  

Language：Japanese   Publisher：(公社)日本小児科学会  

Language：Japanese   Publisher：(一社)日本小児栄養消化器肝臓学会  

Language：Japanese   Publisher：(一社)日本小児栄養消化器肝臓学会  

Language：Japanese   Publisher：Frontiers in Immunology  

Background: Newborn screening (NBS) for severe combined immunodeficiency (SCID) has improved the prognosis of SCID. In Japan, NBS testing (measurement of the T-cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC)) was launched in 2017 and has expanded nationwide in recent years. In this study, we report a Japanese patient with X-linked SCID with a novel IL2RG variant identified through NBS. The patient underwent cord blood transplantation (CBT). Case: The patient had no siblings or family history of inborn errors of immunity. He was born at 38 weeks of gestation and weighed 3,072 g. His NBS results revealed TREC 0 copies/10⁵ cells (normal value: >565 copies/10⁵ cells), which was considered suggestive of SCID. The patient was referred to our hospital. Although his lymphocyte count was 1,402/μL, naïve T cells and CD56⁺ natural killer (NK) cells were decreased to 0% and 0.05% of the total lymphocytes, respectively. Flow cytometric measurement testing revealed a decrease in γc protein expression in the B lymphocytes and NK lymphocytes. We identified a hemizygous novel missense variant (c.256A>C, p.Thr86Pro) of IL2RG. Both in silico and structural analyses revealed that this variant is likely pathogenic. At 3 months of age, he underwent CBT from a human leukocyte antigen-full-matched unrelated donor. The conditioning regimen included fludarabine (180 mg/m²) and targeted busulfan (35 mg×h/L). The patient achieved high-level donor chimerism and immune reconstitution, including B-cell function, at 13 months. Conclusion: Using NBS, the patient was diagnosed as having X-linked SCID with a novel missense variant of IL2RG. Early diagnosis using NBS tests enables safe hematopoietic stem cell transplantation without complications such as infection. We also found that even SCID with novel variants can be accurately diagnosed using the NBS program. In Japan, the test uptake rate is approximately 80% due to the high number of self-funded screening tests, and it is hoped that the uptake rate will increase in the future.

DOI： 10.3389/fimmu.2024.1478411

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PubMed

Language：Japanese   Publisher：Modern Rheumatology  

Objectives: Currently, no indicators on which biologic disease-modifying anti-rheumatic drugs (bDMARDs) should be used first for juvenile idiopathic arthritis (JIA) have been established. Thus, this study aimed to determine the useful biomarkers in JIA to enable the best selection of the first bDMARDs without primary failure. Methods: This retrospective study used data of patients examined for JIA between 2015 and 2021 at Kagoshima University Hospital in Japan. Results: Altogether, 67 cases of non-systemic JIA were analyzed, excluding cases that had been treated for <6 months. Of the 67 cases, 52 were treated with bDMARDs and all rheumatoid factor (RF)+ types (32 cases) were treated with bDMARDs. Eleven cases (31.4&) (all were RF+ types and used anti-tumor necrosis factor (TNF)α agents) switched to other bDMARDs because of primary failure, and nine cases had secondary failure (6;anti-TNF, 3;anti-Interleukin-6). A significant difference in pre-treatment RF values (177.9 vs 25.7 IU/ml, p = 0.002) and presence (Odds Ratio 1.952,p = 0.004) were observed between the primary failure group and effective group. Conclusions: RF+ JIA required bDMARDs with high probability. JIA with high titre of RF tends to be refractory to anti-TNFα agents. Tocilizumab or abatacept could be a first-choice bDMARD in such cases.

DOI： 10.1093/mr/roac125

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PubMed

Language：English   Publisher：Oxford University Press  

若年性特発性関節炎(JIA)において初回導入する生物学的疾患修飾抗リウマチ薬(bDMARD)を選択する際の指標となるバイオマーカーについて検討した。2015年4月～2021年10月に受診した非全身型JIA患者のうち、治療期間6ヵ月未満の患者を除外した67例(女性80.6%、発症時年齢中央値7歳)のデータを後ろ向きに検討した。52例にbDMARDを使用し、リウマトイド因子(RF)陽性例(32例)に対しては全例にbDMARDを使用した。11例がprimary failureをきたして他のbDMARDへの切り替えを行った。それらの患者はいずれもRF陽性で、抗腫瘍壊死因子(TNF)α製剤を使用していた。また9例がsecondary failureに至り、このうち6例は抗TNFα製剤、3例は抗インターロイキン-6製剤を使用していた。Primary failure群と非primary failure群を比較すると、治療前のRF抗体価(177.9 vs 25.7IU/mL、p=0.002)およびRF陽性(オッズ比1.952、p=0.004)に関して有意差が認められた。

Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

Language：Japanese   Publisher：(公社)日本小児科学会  

Language：Japanese   Publisher：(公社)日本小児科学会  

Language：Japanese   Publisher：(公社)日本小児科学会  

症例は11歳女児で、両下肢の紫斑と足関節痛を主訴とした。腹痛も認め症状・経過からIgA血管炎と判断したが、入院時検査で低補体血症と尿潜血および尿蛋白を認め、抗核抗体および抗dsDNA抗体が陽性であったことから、全身性エリテマトーデス(SLE)と診断した。紫斑部位の皮膚生検で血管壁にIgA沈着を認めたため標記の判断となり、ステロイドパルス療法(MPT)後に腎生検を行い、ループス腎炎class IV+Vの診断に至った。下腿の紫斑と腹痛、関節痛はMPT 1クール終了後に消失し再燃しなかった。経過中に帯状疱疹を発症したためアシクロビル経静脈投与を行ったが、SLEの活動性は安定し治療開始9週目に退院した。外来でプレドニゾロン漸減を行っているが、SLE、IgA血管炎ともに再燃なく経過している。

Language：Japanese   Publisher：(一社)日本小児栄養消化器肝臓学会  

Language：Japanese   Publisher：(公社)日本小児科学会  

Language：Japanese   Publisher：Frontiers in Immunology  

Background: Chronic granulomatous disease (CGD) is an inborn immune disorder in which the phagocytic system cannot eradicate pathogens, and autoinflammation occurs. Approximately half of the patients have associated gastrointestinal symptoms. Although most cases with CGD-associated colitis present nonspecific histology, colonoscopy in some cases shows brownish dots over a yellowish oedematous mucosa, which is termed a “leopard sign”. However, the significance of these signs remains unclear. Methods: We collected data from patients with CGD whose colonoscopic findings showed the leopard sign. Results: Three patients with CGD and leopard signs were enrolled in this study. One patient underwent colonoscopy for frequent diarrhoea and weight gain failure, and another for anal fistula. The third patient was without gastrointestinal symptoms and underwent colonoscopy as a screening test before allogeneic haematopoietic cell transplantation (HCT). Endoscopic findings showed a mild leopard sign in the first case; however, non-contiguous and diffuse aphthae were observed throughout the colon. The other two cases were unremarkable except for the leopard sign. All the patients achieved remission with oral prednisolone or HCT. One patient underwent colonoscopy after HCT; results revealed improvements in endoscopy (including the leopard sign) and histological findings. However, another patient underwent colonoscopy after prednisolone treatment; this revealed no change in the leopard sign. Conclusion: The leopard sign in the colon may be a characteristic endoscopic finding of CGD, even in patients who do not develop severe gastrointestinal symptoms; however, it does not reflect the severity of CGD-associated colitis.

DOI： 10.3389/fimmu.2023.1208590

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PubMed

Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese