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Article: [New Complement Therapeutics in Complement-Related Diseases].

Wakamiya, Nobutaka / Ohtani, Katsuki / Hidaka, Yoshihiko / Inoue, Norimitsu

Brain and nerve = Shinkei kenkyu no shinpo

2019 Volume 71, Issue 6, Page(s) 555–564

Abstract: The complement was named after "a complement", a protein molecule that supports an antibody. It was considered previously that the complement mainly participates in protecting against microbial infections. But later, as research on biological functions ... ...

Abstract	The complement was named after "a complement", a protein molecule that supports an antibody. It was considered previously that the complement mainly participates in protecting against microbial infections. But later, as research on biological functions in complement activation advanced drastically, it was elucidated that the complement could be involved in the onset of various diseases. In 2007, eculizumab (ECZ), an anti-C5 (complement factor 5) monoclonal antibody, was approved as a drug for paroxysmal nocturnal hemoglobinuria (PNH) in the United States. In Japan, ECZ was approved for PNH and atypical hemolytic uremic syndrome (aHUS) in 2010 and 2013, respectively. The success of ECZ created an opportunity for drug companies to develop new therapeutics targeting the complement system; development of complement therapeutics is now a major venture of pharmaceutical companies worldwide. Here, I will provide an outline of the approved complement therapeutics and those that are in development and clinical trial phase currently.
MeSH term(s)	Antibodies, Monoclonal, Humanized/therapeutic use ; Atypical Hemolytic Uremic Syndrome/drug therapy ; Clinical Trials as Topic ; Complement C5/antagonists & inhibitors ; Complement Inactivating Agents/therapeutic use ; Complement System Proteins ; Hemoglobinuria, Paroxysmal/drug therapy ; Humans ; Japan
Chemical Substances	Antibodies, Monoclonal, Humanized ; Complement C5 ; Complement Inactivating Agents ; Complement System Proteins (9007-36-7) ; eculizumab (A3ULP0F556)
Language	Japanese
Publishing date	2019-06-06
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	390389-8
ISSN	1344-8129 ; 1881-6096 ; 0006-8969
ISSN (online)	1344-8129
ISSN	1881-6096 ; 0006-8969
DOI	10.11477/mf.1416201316
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Article ; Online: Case report: A family of atypical hemolytic uremic syndrome involving a

Tasaki, Yuko / Tsujimoto, Hiroshi / Yokoyama, Tadafumi / Sugimoto, Naotoshi / Kitajima, Shinji / Fujii, Hiroshi / Hidaka, Yoshihiko / Kato, Noritoshi / Maruyama, Shoichi / Inoue, Norimitsu / Wada, Taizo

Frontiers in immunology

2024 Volume 15, Page(s) 1360855

Abstract: Mutations in the complement factor H ( ...

Abstract	Mutations in the complement factor H (
MeSH term(s)	Humans ; Female ; Infant ; Complement Factor H/genetics ; Atypical Hemolytic Uremic Syndrome/diagnosis ; Atypical Hemolytic Uremic Syndrome/genetics ; Gene Duplication ; Complement System Proteins/genetics ; Mutation ; Blood Proteins/genetics ; Complement C3b Inactivator Proteins/genetics
Chemical Substances	Complement Factor H (80295-65-4) ; Complement System Proteins (9007-36-7) ; CFHR3 protein, human ; Blood Proteins ; CFHR1 protein, human ; Complement C3b Inactivator Proteins
Language	English
Publishing date	2024-03-08
Publishing country	Switzerland
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1360855
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Article ; Online: Assessment of kidney function using inulin-based and estimated glomerular filtration rates before and after allogeneic hematopoietic stem cell transplantation in pediatric patients.

Matsuoka, Daisuke / Hirabayashi, Koichi / Murase, Tsubasa / Saito, Shoji / Hidaka, Yoshihiko / Nakazawa, Yozo

Pediatric blood & cancer

2020 Volume 67, Issue 12, Page(s) e28733

Abstract: Background: Accurate evaluation of kidney function before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is important for both informed decision making and detection of chronic kidney disease. However, to the best of our ... ...

Abstract	Background: Accurate evaluation of kidney function before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is important for both informed decision making and detection of chronic kidney disease. However, to the best of our knowledge, no report has evaluated the glomerular filtration rate (GFR) in pediatric patients who underwent HSCT using the gold standard GFR measurement, as well as inulin-based GFR (iGFR). Methods: We assessed iGFR before and after allo-HSCT to evaluate the impact of allo-HSCT on GFR in a prospective cohort study of 17 pediatric patients. We also assessed the accuracy and bias of the values of estimated GFR (eGFR) calculated using serum creatinine (Cr), cystatin C (CysC), beta-2 microglobulin (β Results: There was no significant difference between the values before and after allo-HSCT. CKiD CysC-, 24hCcr-, and full CKiD-based values showed good within 30% (P30) accuracy (80.6%, 79.3%, and 80.6%, respectively), but only 24hCcr and full CKiD had good mean bias (8.5% and 8.9%, respectively) and narrow 95% limits of agreement (-32.2 to 52.7 mL/min/1.73 m Conclusion: There was no significant impact of allo-HSCT on GFR in our cohort. The most reliable equations for pediatric patients with allo-HSCT were eGFR-24hCcr and eGFR-full CKiD.
MeSH term(s)	Adolescent ; Biomarkers/analysis ; Child ; Child, Preschool ; Creatinine/blood ; Cystatin C/blood ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Hematologic Neoplasms/pathology ; Hematologic Neoplasms/therapy ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Inulin/analysis ; Kidney/physiopathology ; Kidney Function Tests ; Male ; Prognosis ; Prospective Studies
Chemical Substances	Biomarkers ; CST3 protein, human ; Cystatin C ; Inulin (9005-80-5) ; Creatinine (AYI8EX34EU)
Language	English
Publishing date	2020-10-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.28733
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Zs.A 1131: Show issues

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Article ; Online: Childhood asymptomatic renal arteriovenous fistula 5 years after renal biopsy.

Matsuoka, Daisuke / Hidaka, Yoshihiko / Kurozumi, Masahiro / Tsukahara, Yoshinori / Nakazawa, Yozo

Pediatrics international : official journal of the Japan Pediatric Society

2018 Volume 60, Issue 6, Page(s) 601–602

MeSH term(s)	Adolescent ; Arteriovenous Fistula/diagnostic imaging ; Arteriovenous Fistula/etiology ; Asymptomatic Diseases ; Biopsy/adverse effects ; Child ; Female ; Humans ; Incidental Findings ; Kidney/pathology ; Renal Artery/diagnostic imaging ; Renal Artery/pathology ; Renal Veins/diagnostic imaging ; Renal Veins/pathology ; Ultrasonography, Doppler
Language	English
Publishing date	2018-05-16
Publishing country	Australia
Document type	Case Reports ; Journal Article
ZDB-ID	1470376-2
ISSN	1442-200X ; 1328-8067
ISSN (online)	1442-200X
ISSN	1328-8067
DOI	10.1111/ped.13571
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Zs.A 848: Show issues

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Article ; Online: Anti-complement factor H (CFH) antibodies and a novel

Minato, Sonoko / Iijima, Hiroyuki / Nakao, Hiro / Nishi, Kentaro / Hidaka, Yoshihiko / Inoue, Norimitsu / Kubota, Mitsuru / Ishiguro, Akira

Immunological medicine

2021 Volume 44, Issue 4, Page(s) 274–277

Abstract: Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by overactivation of the complement alternative pathway. aHUS involves the presence of antibodies against complement factor H and its mutations in the complement genes. A 2-month-old boy ... ...

Abstract	Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by overactivation of the complement alternative pathway. aHUS involves the presence of antibodies against complement factor H and its mutations in the complement genes. A 2-month-old boy presented with discoid rash, hemolytic anemia, thrombocytopenia, multiple antibodies, and hypocomplementemia with a very low level of C4 (< 3 mg/dL), indicating activation of the complement pathway, together fulfilling the systemic lupus erythematosus (SLE) criteria of the American College of Rheumatology at 5 months of age. However, most of these findings normalized spontaneously without any intervention. Further investigations revealed a high level of anti-complement factor H antibodies and a novel heterozygous missense mutation (p.Glu1172Ala, located in exon 22) in a complement gene,
MeSH term(s)	Atypical Hemolytic Uremic Syndrome/genetics ; Complement Activation ; Complement Factor H/genetics ; Complement System Proteins ; Humans ; Infant ; Male ; Mutation
Chemical Substances	Complement Factor H (80295-65-4) ; Complement System Proteins (9007-36-7)
Language	English
Publishing date	2021-03-30
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	2578-5826
ISSN (online)	2578-5826
DOI	10.1080/25785826.2021.1905303
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Article ; Online: Immune-complex glomerulonephritis with a membranoproliferative pattern in Frasier syndrome: a case report and review of the literature.

Matsuoka, Daisuke / Noda, Shunsuke / Kamiya, Motoko / Hidaka, Yoshihiko / Shimojo, Hisashi / Yamada, Yasushi / Miyamoto, Tsutomu / Nozu, Kandai / Iijima, Kazumoto / Tsukaguchi, Hiroyasu

BMC nephrology

2020 Volume 21, Issue 1, Page(s) 362

Abstract: Background: Mutations in the Wilms tumor 1 gene cause a spectrum of podocytopathy ranging from diffuse mesangial sclerosis to focal segmental glomerulosclerosis. In a considerable fraction of patients with Wilms tumor 1 mutations, the distinctive ... ...

Abstract	Background: Mutations in the Wilms tumor 1 gene cause a spectrum of podocytopathy ranging from diffuse mesangial sclerosis to focal segmental glomerulosclerosis. In a considerable fraction of patients with Wilms tumor 1 mutations, the distinctive histology of immune-complex-type glomerulonephritis has been reported. However, the clinical relevance and etiologic mechanisms remain unknown. Case presentation: A 5-year-old child presented with steroid-resistant nephrotic range proteinuria. Initial renal biopsy revealed predominant diffuse mesangial proliferation with a double-contour and coexisting milder changes of focal segmental glomerulosclerosis. Immunofluorescence and electron microscopy revealed a full-house-pattern deposition of immune complexes in the subendothelial and paramesangial areas. Serial biopsies at 6 and 8 years of age revealed that more remarkable changes of focal segmental glomerulosclerosis had developed on top of the initial proliferative glomerulonephritis. Identification of a de novo Wilms tumor 1 splice donor-site mutation in intron 9 (NM_024426.6:c.1447 + 4C > T) and 46,XY-gonadal dysgenesis led to the diagnosis of Frasier syndrome. Conclusions: Our findings, together with those of others, point to the importance of heterogeneity in clinicopathological phenotypes caused by Wilms tumor 1 mutations and suggest that immune-complex-mediated membranoproliferative glomerulopathy should be considered as a histological variant.
MeSH term(s)	Antigen-Antibody Complex ; Child ; Child, Preschool ; Disease Progression ; Frasier Syndrome/genetics ; Frasier Syndrome/pathology ; Glomerulonephritis, Membranoproliferative/pathology ; Glomerulosclerosis, Focal Segmental/pathology ; Humans ; Kidney/pathology ; Male ; WT1 Proteins/genetics
Chemical Substances	Antigen-Antibody Complex ; WT1 Proteins ; WT1 protein, human
Language	English
Publishing date	2020-08-24
Publishing country	England
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	2041348-8
ISSN	1471-2369 ; 1471-2369
ISSN (online)	1471-2369
ISSN	1471-2369
DOI	10.1186/s12882-020-02007-0
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Article ; Online: Characterization of cytoskeletal and structural effects of INF2 variants causing glomerulopathy and neuropathy.

Scientific reports

2023 Volume 13, Issue 1, Page(s) 12003

Abstract: Focal segmental glomerulosclerosis (FSGS) is a common glomerular injury leading to end-stage renal disease. Monogenic FSGS is primarily ascribed to decreased podocyte integrity. Variants between residues 184 and 245 of INF2, an actin assembly factor, ... ...

Abstract	Focal segmental glomerulosclerosis (FSGS) is a common glomerular injury leading to end-stage renal disease. Monogenic FSGS is primarily ascribed to decreased podocyte integrity. Variants between residues 184 and 245 of INF2, an actin assembly factor, produce the monogenic FSGS phenotype. Meanwhile, variants between residues 57 and 184 cause a dual-faceted disease involving peripheral neurons and podocytes (Charcot-Marie-Tooth CMT/FSGS). To understand the molecular basis for INF2 disorders, we compared structural and cytoskeletal effects of INF2 variants classified into two subgroups: One (G73D, V108D) causes the CMT/FSGS phenotype, and the other (T161N, N202S) produces monogenic FSGS. Molecular dynamics analysis revealed that all INF2 variants show distinct flexibility compared to the wild-type INF2 and could affect stability of an intramolecular interaction between their N- and C-terminal segments. Immunocytochemistry of cells expressing INF2 variants showed fewer actin stress fibers, and disorganization of cytoplasmic microtubule arrays. Notably, CMT/FSGS variants caused more prominent changes in mitochondrial distribution and fragmentation than FSGS variants and these changes correlated with the severity of cytoskeletal disruption. Our results indicate that CMT/FSGS variants are associated with more severe global cellular defects caused by disrupted cytoskeleton-organelle interactions than are FSGS variants. Further study is needed to clarify tissue-specific pathways and/or cellular functions implicated in FSGS and CMT phenotypes.
MeSH term(s)	Humans ; Microfilament Proteins/metabolism ; Glomerulosclerosis, Focal Segmental/complications ; Formins/genetics ; Actins/genetics ; Mutation ; Cytoskeleton/metabolism ; Podocytes/metabolism
Chemical Substances	Microfilament Proteins ; Formins ; Actins ; INF2 protein, human
Language	English
Publishing date	2023-07-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-38588-7
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Article ; Online: Immunological risk and complement genetic evaluations in early onset de novo thrombotic microangiopathy after living donor kidney transplantation: A Japanese multicenter registry.

Clinical and experimental nephrology

2023 Volume 27, Issue 12, Page(s) 1010–1020

Abstract: Background: Thrombotic microangiopathy (TMA) after kidney transplantation (KTx), particularly early onset de novo (dn) TMA, requires immediate interventions to prevent irreversible organ damage. This multicenter study was performed to investigate the ... ...

Abstract	Background: Thrombotic microangiopathy (TMA) after kidney transplantation (KTx), particularly early onset de novo (dn) TMA, requires immediate interventions to prevent irreversible organ damage. This multicenter study was performed to investigate the allogeneic clinical factors and complement genetic background of dnTMA after KTx. Methods: Perioperative dnTMA after KTx within 1 week after KTx were diagnosed based on pathological or/and hematological criteria at each center, and their immunological backgrounds were researched. Twelve aHUS-related gene variants were examined in dnTMA cases. Results: Seventeen recipients (15 donors) were enrolled, and all dnTMA cases were onset within 72-h of KTx, and 16 of 17 cases were ABO incompatible. The implementation rate of pre-transplant plasmaphereses therapies were low, including cases with high titers of anti-A/anti-B antibodies. Examination of aHUS-related gene variants revealed some deletions and variants with minor allele frequency (MAF) in Japan or East Asian genome databases in genes encoding alternative pathways and complement regulatory factors. These variants was positive in 8 cases, 6 of which were positive in both recipient and donor, but only in one graft loss case. Conclusions: Although some immunological risks were found for dnTMA after KTx, only a few cases developed into TMA. The characteristic variations revealed in the present study may be novel candidates related to dnTMA in Japanese or Asian patients, but not pathogenic variants of aHUS. Future studies on genetic and antigenic factors are needed to identify factors contributing to dnTMA after KTx.
MeSH term(s)	Humans ; Kidney Transplantation/adverse effects ; Living Donors ; East Asian People ; Retrospective Studies ; Thrombotic Microangiopathies/etiology ; Thrombotic Microangiopathies/genetics ; Complement System Proteins/genetics
Chemical Substances	Complement System Proteins (9007-36-7)
Language	English
Publishing date	2023-08-27
Publishing country	Japan
Document type	Multicenter Study ; Journal Article
ZDB-ID	1338768-6
ISSN	1437-7799 ; 1342-1751
ISSN (online)	1437-7799
ISSN	1342-1751
DOI	10.1007/s10157-023-02391-5
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Zs.A 4922: Show issues

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Article ; Online: Correction to: Immunological risk and complement genetic evaluations in early onset de novo thrombotic microangiopathy after living donor kidney transplantation: A Japanese multicenter registry.

Clinical and experimental nephrology

2023 Volume 27, Issue 12, Page(s) 1021–1022

Language	English
Publishing date	2023-10-20
Publishing country	Japan
Document type	Published Erratum
ZDB-ID	1338768-6
ISSN	1437-7799 ; 1342-1751
ISSN (online)	1437-7799
ISSN	1342-1751
DOI	10.1007/s10157-023-02409-y
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Article ; Online: High vaccination coverage is associated with low epidemic level of seasonal influenza in elementary schools: an observational study in Matsumoto City, Japan.

Uchida, Mitsuo / Kaneko, Minoru / Hidaka, Yoshihiko / Yamamoto, Hiroshi / Honda, Takayuki / Takeuchi, Shouhei / Saito, Masaya / Kawa, Shigeyuki

BMC infectious diseases

2018 Volume 18, Issue 1, Page(s) 128

Abstract: Background: Influenza virus transmission may be prevented by infection control measures, including vaccination, wearing a mask, gargling with water, and hand washing. It is unclear, however, whether these measures affect influenza epidemics in school ... ...

Abstract	Background: Influenza virus transmission may be prevented by infection control measures, including vaccination, wearing a mask, gargling with water, and hand washing. It is unclear, however, whether these measures affect influenza epidemics in school settings. Methods: A prospective epidemiological survey in all public elementary schools in Matsumoto City, Japan, during the 2014/2015 season evaluated the number of diagnosed patients in each school and calculated the reproduction number of schoolchildren. At the end of the prospective survey, a cross-sectional survey evaluated the implementation of infection control measures in these schools. Both results were combined and associations among infection control measures including vaccination, mask wearing, hand washing, water gargling, and epidemic level were evaluated. Results: Of the 13,217 schoolchildren in 29 schools, 2548 were diagnosed with seasonal influenza. A significant negative association was observed between vaccination coverage and reproduction number at each school, but not between other infection control measures and the reproduction number. A regression curve with exponential function was most predictive. At 0% vaccination, the reproduction number was estimated to be 1.39. Conclusion: These findings provide evidence that high vaccination coverage was associated with reduced epidemic levels in schools and suggest the need for increased vaccination of schoolchildren.
MeSH term(s)	Child ; Cities ; Epidemics ; Female ; Humans ; Infection Control ; Influenza Vaccines/immunology ; Influenza, Human/diagnosis ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Japan/epidemiology ; Linear Models ; Male ; Prospective Studies ; Schools ; Seasons ; Surveys and Questionnaires ; Vaccination Coverage
Chemical Substances	Influenza Vaccines
Language	English
Publishing date	2018--13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1471-2334
ISSN (online)	1471-2334
DOI	10.1186/s12879-018-3025-9
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