Immunological Medicine

Immune thrombocytopenia (ITP) is a thrombocytopenic condition induced by autoimmune mechanisms and includes secondary ITP with underlying diseases such as connective tissue diseases (CTD). In recent years, it has been elucidated that the subsets of the ITP are associated with complement abnormalities but much remains unclear. To perform a literature review and identify the characteristics of complement abnormalities in ITP. PUBMED was used to collect the literature published up to June 2022 related to ITP and complement abnormalities. Primary and secondary ITP (CTD-related) were examined. Out of the collected articles, 17 were extracted. Eight articles were related to primary ITP (pITP) and 9 to CTD-related ITP. Analysis of the literature revealed that the ITP severity was inversely correlated with serum C3, C4 levels in both ITP subgroups. In pITP, a wide range of complement abnormalities was reported, including abnormalities of initial proteins, complement regulatory proteins, or the end products. In CTD-related ITP, reported complement abnormalities were limited to the initial proteins. Activation of the early complement system, mainly through activation of C3 and its precursor protein C4, was reported for both ITPs. On the other hand, more extensive complement activation has been reported in pITP.

Risa Shindo

Ryohei Abe

Kenji Oku

Tomoki Tanaka

Yu Matsueda

Tatsuhiko Wada

Yoshiyuki Arinuma

Sumiaki Tanaka

Tatsuyoshi Ikenoue

Yoshitaka Miyakawa

Kunihiro Yamaoka

Involvement of the complement system in immune thrombocytopenia: review of the literature

补体系统在免疫性血小板减少症中的作用：文献综述

Trained immunity (TI) is functional memory displayed by innate immune cells (IICs). TI facilitates rapid, non-specific responses to pathogens upon secondary challenge. It is driven by immunological signaling and metabolic rewriting via epigenetic alteration, triggered by recognition of certain stimuli. Recently, immune checkpoint inhibitors have come into common use in clinical oncology settings, and genetically engineered cytotoxic T cells comprise a potent cancer treatment strategy. However, the contributions of TI in the tumor microenvironment (TME) are only beginning to be uncovered. Accumulating evidence that various microorganisms and vaccines convey tumoricidal ability suggest that TI may become a useful anti-cancer tool. The expected roles of TI in tumor therapy are the 1) promotion of proinflammatory cytokine section, 2) enhancement of phagocytosis, 3) quick expansion and recruitment of cancer-specific cytotoxic T cells to the TME through neoantigen presentation, 4) reversal of immunosuppression in the TME, and 5) removal of pathogens associated with carcinogenesis or tumor development. Medium- to long-term TI durability may reduce the risk of tumor development. Recent findings on TI usher in new aspirations for cancer treatment.

Hiroyuki Takahashi

Daibo Kojima

Masato Watanabe

Therapeutic potential of trained immunity for malignant disease

恶性疾病的训练免疫治疗潜力

X-linked NF-κB essential modulator (NEMO) deficiency is a primary immunodeficiency characterized by combined immunodeficiency and ectodermal dysplasia. Monocytes from the patients demonstrate a severely impaired response to tissue necrosis factor or lipopolysaccharide, whereas hyper-inflammation is found in some patients. Juvenile myelomonocytic leukemia (JMML) is a pediatric malignancy caused by hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) and aberrant RAS signaling activation. Patients with JMML demonstrate characteristic manifestations such as splenomegaly, monocytosis and the presence of myeloid or erythroid precursors in the peripheral blood. Here, we present the case of a male infant with ectodermal dysplasia, bacterial septicemia, Pneumocystis pneumonia, severe inflammation and transient manifestations mimicking JMML. Genetic analysis revealed a deep intronic germline variant of IKBKG. Full-length IKBKG cDNA and NEMO protein expression were almost inexistent. Peripheral mononuclear cells (PBMCs) from the patient showed increased RAS signaling activation with GM-CSF or Phorbol 12-myristate 13-acetate without the RAS-associated gene variant, although the increased RAS signaling activation in induced-pluripotent stem cell-derived myeloid lineage and bone marrow-derived mesenchymal cells was not evident. The patient with NEMO deficiency demonstrated JMML-like manifestation and severe inflammation. PBMCs of the patient demonstrated increased RAS signaling activation with unknown pathophysiology.

Masahiro Ueki

Shinsuke Hirabayashi

Yoshitaka Honda

Shunichiro Takezaki

Hiroki Ohata

Shimaa Said Mohamed Ali Abdrabou

Saori Sawai

Yukayo Terashita

Yuko Cho

Hideki Muramatsu

Kazushi Izawa

Takahiro Yasumi

Yoshiyuki Takahashi

Masafumi Yamada

Atsushi Manabe

Increased response to granulocyte-macrophage colony-stimulating factor in peripheral blood cells and transient manifestations mimicking juvenile myelomonocytic leukemia in a male patient with NEMO deficiency caused by a deep intronic pathogenic variant of IKBKG

NEMO缺陷症男性患者外周血细胞对粒细胞-巨噬细胞集落刺激因子反应增强及短暂性幼年型粒单核细胞白血病样表现，由IKBKG基因深内含子致病变异引起

We sought to clarify the musculoskeletal ultrasound (MSUS) findings and serum concentrations of cytokines/growth factors in glucocorticoid-resistant polymyalgia rheumatica (GC-R PMR). Patients with PMR admitted to Nagasaki University Hospital (n = 41) were enrolled. MSUS of both shoulder joints was performed in 36 patients. Patients' sera were analyzed for cytokines/growth factors using multiplex assay kits. We examined the cases of 17 males and 24 females (median age 70 years). There were 27 GC-R patients and 14 non-GC-R patients. PD signals were detected in significantly more GC-R patients (65.2%) than non-GC-R patients (23.1%) (p = 0.035). The median serum level of vascular endothelial growth factor (VEGF) was significantly higher in the GC-R group at 871.4 pg/mL than the non-GC-R group (422.8 pg/mL) (p = 0.03) and significantly higher in the PD-positive versus PD-negative patients (p = 0.04). A multivariate analysis revealed that a high serum VEGF level was an independent variable contributing to GC resistance (p = 0.017, odds ratio: 10.34). These results suggest that a high serum VEGF level is a biomarker of GC resistance in PMR, which might be explained by PD-positive neovascularization in inflamed joints of PMR.

Tomoki Origuchi

Masataka Umeda

Shoichi Fukui

Kaori Furukawa

Toshimasa Shimizu

Remi Sumiyoshi

Tomohiro Koga

Shin-ya Kawashiri

Naoki Iwamoto

Mami Tamai

Kazuhiko Arima

Atsushi Kawakami

Analysis of musculoskeletal ultrasound findings and cytokines/growth factors in glucocorticoid-resistant polymyalgia rheumatica

糖皮质激素抵抗性风湿性多肌痛中肌肉骨骼超声表现与细胞因子/生长因子的分析

Interleukin-1, a pro-inflammatory cytokine, plays a crucial role in inflammatory disease pathogenesis. Interleukin-1 receptor antagonist knockout (IL-1Ra KO) mice spontaneously develop aortitis, arthritis and dermatitis, and are employed as a model for human inflammatory diseases. Previous studies have shown that transferring total T cells from IL-1Ra KO mice into nude mice induces aortitis and arthritis; however, the roles of specific T cell subsets in these inflammatory responses remain unclear. In this study, we aimed to investigate the T cell subsets in IL-1Ra KO mice. We found that the proportion of PD-1+CD44+CD62L-CD4+ T cells in the spleen and lymph nodes of IL-1Ra KO mice was significantly higher than that of wild type mice. RNA sequencing revealed elevated expression of basic helix-loop-helix family member e40 and granulocyte macrophage colony stimulating factor (GM-CSF) in splenic CD44+CD62L-CD4+ T cells from IL-1Ra KO mice. In addition, GM-CSF production from splenic CD4+ T cells of IL-1Ra KO mice was significantly higher than that of wild type mice when stimulated with PMA and ionomycin in vitro. Notably, immunohistochemical staining showed infiltration of GM-CSF+CD4+ T cells at inflammatory sites in IL-1Ra KO mice. Our results suggest that a subset of GM-CSF+CD4 + T cells emerges under IL-1 signal-enhanced inflammatory conditions.

Sho Ishigaki

Keiko Yoshimoto

Mitsuhiro Akiyama

Kotaro Matsumoto

Katsuya Suzuki

Kazuhiro Yamanoi

Yoichiro Iwakura

Tsutomu Takeuchi

Yuko Kaneko

Expansion of granulocyte-macrophage colony-stimulating factor producing CD4+ T cells in an animal model with enhanced interleukin-1 signal

增强白细胞介素-1信号的动物模型中粒细胞-巨噬细胞集落刺激因子产生CD4+ T细胞的扩增

We started a registry for cases of immunoglobulin (Ig)G4-related disease (IgG4-RD) in December 2019 to clarify the clinical profile of IgG4-RD. In this study, clinical information from 854 cases registered by February 16, 2024 was analyzed from multiple perspectives. Diagnosis of IgG4-RD was made in 808 cases, comprising 638 definite, 38 probable, and 132 possible. The mean ± SD age at time of enrollment of the 808 cases was 67.9 ± 11.3 years, with 68.8% being male. The pancreas was the most frequently affected organ (49.8%), followed by the submandibular glands (46.2%) and lacrimal glands (30.6%). This study reconfirmed the pancreas and head-and-neck region as major affected areas in IgG4-RD. Clinically, submandibular adenitis and autoimmune pancreatitis often occur together in the same patient, but no association between the two organs was observed in our analysis. Regarding diagnosis, the comprehensive diagnostic criteria were most commonly used (63.6%). Storiform fibrosis and phlebitis obliterans were detected at different frequencies in different organs. In summary, this registry study identified clinical, imaging, hematologic, and pathologic findings in 808 Japanese patients with IgG4-RD. The frequency of affected organs and their characteristic pathological findings will be particularly useful for future practice.

Motohisa Yamamoto

Masatoshi Kanda

Ichiro Mizushima

Atsushi Kanno

Takeji Umemura

Tsukasa Ikeura

Yuzo Kodama

Hiroaki Dobashi

Yoshiya Tanaka

Atsushi Masamune

Masafumi Moriyama

Takako Saeki

Shoko Matsui

Yasufumi Masaki

Masanori Asada

Hisanori Umehara

Hiroshi Seno

Itaru Naitoh

Satoshi Yamamoto

Eisuke Iwasaki

Kensuke Kubota

Shiroh Tanoue

Takayoshi Nishino

Hiroto Tsuboi

Yasushi Matsumoto

Hiroyuki Isayama

Hiroshi Goto

Kenji Notohara

Kazushige Uchida

Ken Kawabe

Kazunori Yamada

Satomi Kasashima

Masayuki Takahira

Yasuharu Sato

Izumi Kawachi

Izumi Yamaguchi

Kazuichi Okazaki

Seiji Nakamura

Fumihiko Matsuda

Hideki Ishikawa

Mitsuhiro Kawano

Masanari Sugawara

Shunsuke Tsuge

Kensuke Yokoyama

Eriko Ikeda

Kozue Ando

Akira Nakamura

Ayaka Takaori

Takeshi Ito

Koh Nakamaru

Noriko Juri

Hiromi Shimada

Shingo Nakayamada

Satoshi Kubo

Yuya Fujita

Yoshino Inoue

Takanori Sano

Tetsuya Takikawa

Yuka Miyahara

Hajime Yoshifuji

Tomohiro Handa

Masataka Yokode

Clinical profile of IgG4-related disease in Japan based on the rare disease data registry

基于罕见病数据登记的日本IgG4相关疾病临床特征

Abbreviation	Immunol. Med.
Journal Impact	2.62
Quartiles(Global)	RHEUMATOLOGY(Q2)

ISSN	2578-5826
h-index	22

Publication Information	Publisher: Taylor and Francis Ltd.，Publishing cycle: ，Journal Type: journal，Open Access Journals: Yes
Basic data	Year of publication: 2018，Proportion of original research papers: 60.00%，Self Citation Rate:3.70%， Gold OA Rate: 98.89%
Journal Fees	$1680Details
Average review cycle	网友分享经验：19 Weeks

Immunological Medicine

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Involvement of the complement system in immune thrombocytopenia: review of the literature

Therapeutic potential of trained immunity for malignant disease

Increased response to granulocyte-macrophage colony-stimulating factor in peripheral blood cells and transient manifestations mimicking juvenile myelomonocytic leukemia in a male patient with NEMO deficiency caused by a deep intronic pathogenic variant of IKBKG

Analysis of musculoskeletal ultrasound findings and cytokines/growth factors in glucocorticoid-resistant polymyalgia rheumatica

Expansion of granulocyte-macrophage colony-stimulating factor producing CD4+ T cells in an animal model with enhanced interleukin-1 signal

Therapeutic potential of trained immunity for malignant disease

Clinical profile of IgG4-related disease in Japan based on the rare disease data registry

Expansion of granulocyte-macrophage colony-stimulating factor producing CD4+ T cells in an animal model with enhanced interleukin-1 signal

Analysis of musculoskeletal ultrasound findings and cytokines/growth factors in glucocorticoid-resistant polymyalgia rheumatica

Increased response to granulocyte-macrophage colony-stimulating factor in peripheral blood cells and transient manifestations mimicking juvenile myelomonocytic leukemia in a male patient with NEMO deficiency caused by a deep intronic pathogenic variant of IKBKG