Updated on 2026/03/06

写真a

 
FUKUI Sosuke
 
Organization
Graduate School of Medicine Department of Renal Replacement Therapy Endowed Chair Designated Assistant Professor
Title
Designated Assistant Professor

Degree 2

  1. 医学博士 ( 2024.4   名古屋大学 ) 

  2. 医学学士 ( 2010.3   岐阜大学 ) 

 

Papers 12

  1. Peritoneal Expression of Membrane Complement Regulators Is Decreased in Peritoneal Dialysis Patients with Infected Peritonitis Reviewed Open Access

    Fukui, S; Mizuno, M; Tawada, M; Suzuki, Y; Kojima, H; Matsukawa, Y; Imai, M; Kim, H; Kinashi, H; Mizutani, M; Minoshima, K; Maruyama, S; Ito, Y

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Vol. 24 ( 11 )   2023.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:International Journal of Molecular Sciences  

    In peritoneal dialysis (PD) patients, fungi and Pseudomonas aeruginosa are considered important causative microorganisms for peritonitis with poor prognosis. Our objective was to explore expressions of membrane complement (C) regulators (CRegs) and tissue injuries in the peritoneum of patients with PD-related peritonitis, including fungal and Pseudomonas aeruginosa peritonitis. In peritoneal biopsy tissues obtained at PD catheter removal, we investigated the severity of peritonitis-associated peritoneal injuries and the expression of CRegs, CD46, CD55, and CD59 against peritoneal tissues without any episode of peritonitis. In addition, we evaluated peritoneal injuries among fungal and Pseudomonas aeruginosa-peritonitis (P1) and Gram-positive bacterial peritonitis (P2). We also observed deposition of C activation products such as activated C and C5b-9 and measured sC5b-9 in the PD fluid of patients. As a result, the severity of peritoneal injuries correlated inversely with the expression of peritoneal CRegs. Peritoneal CReg expression in peritonitis was significantly reduced compared to no peritonitis. Peritoneal injuries were more severe in P1 than in P2. CReg expression was further decreased and C5b-9 further increased in P1 than in P2. In conclusion, severe peritoneal injuries due to fungal and Pseudomonas aeruginosa-peritonitis decreased CReg expression and increased deposition of activated C3 and C5b-9 in the peritoneum, suggesting that peritonitis, particularly fungal and Pseudomonas aeruginosa-peritonitis, might induce susceptibility to further peritoneal injuries due to excessive C activation.

    DOI: 10.3390/ijms24119146

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  2. Absence of complement terminal pathway activity in C6-deficient mice prolongs survival in a mouse model of severe malarial infection Open Access

    Kamiya, T; Miyasaka, Y; Kim, H; Fukui, S; Inoue, M; Ishigami, M; Suzuki, Y; Maruyama, S; Ohno, T; Hughes, TR; Morgan, BP; Mizuno, M

    IMMUNOBIOLOGY   Vol. 230 ( 6 ) page: 153140   2025.11

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    Language:English   Publisher:Immunobiology  

    Background: Malaria is an important and serious parasite-induced disease associated with severe anemia and multiple organ failure (MOF) that can be lethal in humans. We explored the contribution of the terminal pathway of complement in a mouse model of malaria-induced lethal MOF following infection with Plasmodium (P.) bergei. Methods: We compared organ damage and survival between C57BL/6 J mice deficient in the terminal pathway component C6 (C6def) and wild type C57BL/6 J mice (WT) after intraperitoneal injection of 10<sup>6</sup> P. bergei-parasitized erythrocytes. We measured survival, relevant blood parameters, assessed severity of injury and complement activation in relevant organs. Results: All WT mice died between 7 and 13 days after exposure to the parasite challenge; in contrast, C6def mice showed prolonged survival with 80 % alive at day 20, although all then died by day 26. Parasite load and anemia at day 7 were similar in C6def and WT mice. Liver and lung injuries, fibrosis and organ complement deposition assessed at day 7 post-infection were significantly milder in C6def mice compared to WT. Blood platelet count at day 7 post-infection was markedly reduced in WT but not in C6def mice; in contrast, white cell count was increased and hemoglobin levels decreased to similar degrees in WT and C6def mice post-infection. Albumin levels were reduced, significantly more in WT, while blood markers of liver injury were increased, significantly more in WT. Serum levels of complement activation product, C5a, and IL6 were increased in both groups, the latter significantly higher in WT versus C6def mice. Conclusion: We show that complement terminal pathway activation exacerbates organ injuries and thrombocytopenia associated with P. bergei infection, contributing to rapid progression to death in the model. Inhibition of terminal pathway activation in human malarial infections using available drugs might slow progression to organ failure, extending the window of opportunity for the effective use of anti-malarial medicines.

    DOI: 10.1016/j.imbio.2025.153140

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  3. 特集 透析療法の課題,展望 総論 腹膜透析の現状と残された課題

    水野 正司, 金 恒秀, 福井 聡介, 鈴木 康弘

    腎と透析   Vol. 98 ( 1 ) page: 13 - 17   2025.1

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    Publisher:東京医学社  

    DOI: 10.24479/kd.0000001734

    CiNii Research

  4. Delaying treatment for peritonitis could be related to longer hospitalization in patients on peritoneal dialysis Open Access

    Koshitori, Y; Takai, N; Isomura, Y; Hiramatsu, T; Suzuki, Y; Kim, H; Fukui, S; Mizuno, M

    RENAL REPLACEMENT THERAPY   Vol. 10 ( 1 )   2024.11

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    Publisher:Renal Replacement Therapy  

    Background: When peritoneal dialysis (PD)-related peritonitis occurs in PD patients, diagnostic and therapeutic approaches should be started as soon as possible. However, medical attention may be delayed in patients experiencing minimal symptoms with cloudy PD fluid (PDF). This study investigated differences between the first and later episodes of peritonitis and relationships between interval from peritonitis onset to attending hospital and both duration of hospitalization and medical expenses. Methods: We retrospectively investigated 36 patients with multiple episodes of PD-related peritonitis among 125 patients receiving PD therapy from January 2016 during a 6-year period at a single center. Results: In 50 episodes of PD-related peritonitis among outpatients, median interval from recognition of cloudy PDF to hospital visit was 4.0 h (interquartile range [IQR] 2.0–12.0 h). With the first episode of peritonitis, the median interval was 8.5 h (IQR 3.6–18.0 h), improving to 2.0 h (IQR2.0–3.3 h) with second and subsequent episodes of peritonitis after patients were provided with education in PD-related issues. Median duration of hospitalization associated with PD-related peritonitis was 16.0 days (IQR 14–22 days) when the interval to hospital visit was < 6 h, significantly shorter than the 20 days (IQR 16–39 days) when the interval from the patient recognizing peritonitis to hospital visit was ≥ 6 h. Conclusions: Our results suggest that delaying the hospital visit might lead to longer duration of hospitalization, suggesting that effective educational approaches might be warranted to change behaviors during initial peritonitis.

    DOI: 10.1186/s41100-024-00587-3

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  5. Urinary sC5b-9 levels predict residual renal function reservation in peritoneal dialysis patients

    Mizuno, M; Oshima, A; Higashide, K; Suzuki, M; Fukui, S; Suzuki, Y; Kim, H

    EUROPEAN JOURNAL OF IMMUNOLOGY   Vol. 54   page: 94 - 94   2024.9

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  6. Effectiveness of additional topical antibiotics for recurrent or refractory exit-site infection: a case series Reviewed Open Access

    Asai, N; Suzuki, Y; Asai, A; Kinashi, H; Kamiya, K; Hagita, J; Matsuoka, N; Kawamura, S; Fukui, S; Kim, H; Yamaguchi, M; Katsuno, T; Mizuno, M; Ishimoto, T; Ito, Y

    RENAL REPLACEMENT THERAPY   Vol. 10 ( 1 )   2024.6

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    Publisher:Renal Replacement Therapy  

    Background: Japanese peritoneal dialysis (PD) guidelines do not suggest applying mupirocin/gentamicin ointment to the exit sites of PD patients to prevent exit-site infection (ESI). The guidelines do not mention topical antimicrobials as a treatment for ESI. Methods: We retrospectively investigated the additional use of topical antibiotic ointments on patients receiving oral or intravenous antibiotics for recurrent and/or refractory ESI at Aichi Medical University and Nagoya University Hospitals between 2017 and 2022. Results: A total of 13 patients (11 men, 2 women) were included in this study. Median age was 69.0 years, median duration of PD was 26.0 months, two patients had diabetes as a complication, and ESI incidence was 2.7 episodes per patient-year. Systemic antibacterial treatment had been administered for a median of 27.0 days before application therapy. Mupirocin was used in eight cases and gentamicin in five cases, with complete resolution in all cases. No adverse effects such as skin symptoms, antibiotic resistance, or non-tuberculous mycobacterial infections were observed. Cases were divided into two groups based on the duration of topical antibiotic use: short-term group < 90 days and long-term group ≥ 90 days. All patients in both groups achieved complete resolution, with no significant differences in time to resolution, number of recurrent ESIs, or occurrence of ESIs after discontinuation of application therapy. Conclusion: Additional use of topical antibiotic for recurrent and/or refractory ESI appears safe and effective. This study suggests that future randomized controlled trials are warranted.

    DOI: 10.1186/s41100-024-00547-x

    Open Access

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  7. Complement terminal pathway inhibition reduces peritoneal injuries in a rat peritonitis model Reviewed Open Access

    Kamegai, N; Kim, H; Suzuki, Y; Fukui, S; Kojima, H; Maruyama, S; Morgan, BP; Zelek, WM; Mizuno, M

    CLINICAL AND EXPERIMENTAL IMMUNOLOGY   Vol. 214 ( 2 ) page: 209 - 218   2023.12

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    Language:English   Publisher:Clinical and Experimental Immunology  

    Peritonitis and the resulting peritoneal injuries are common problems that prevent long-term peritoneal dialysis (PD) therapy in patients with end-stage kidney diseases. Previously, we have analyzed the relationship between the complement system and progression of peritoneal injuries associated with PD, particularly focusing on the early activation pathways and effects of the anaphylatoxins. We here utilized a novel mAb 2H2 that blocks assembly of the membrane attack complex (MAC) to investigate roles of the complement terminal pathway in PD-associated peritoneal injury. We intraperitoneally injected mAb 2H2 anti-C5b-7 (2.5 or 5 mg/rat) once or twice over the five-day course of the experiment to investigate the effects of inhibiting formation of MAC in a fungal rat peritonitis model caused by repeated intraperitoneal administration of zymosan after methylglyoxal pretreatment (Zy/MGO model). Rats were sacrificed on day 5 and macroscopic changes in both parietal and visceral peritoneum evaluated. Peritoneal thickness, the abundance of fibrinogen and complement C3 and MAC deposition in tissue and accumulation of inflammatory cells were pathologically assessed. The results showed that mAb 2H2, but not isotype control mAb, reduced peritoneal thickness and accumulation of inflammatory cells in a dose and frequency-dependent manner in the Zy/MGO model. These effects were accompanied by decreased C3, MAC, and fibrinogen deposition in peritoneum. In conclusion, in the rat Zy/MGO model, complement terminal pathway activation and MAC formation substantially contributed to development of peritoneal injuries, suggesting that MAC-targeted therapies might be effective in preventing development of peritoneal injuries in humans.

    DOI: 10.1093/cei/uxad088

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  8. Prevention of terminal pathway activation improves survival in a lethal malarial infection mouse model associated with multiple organ failure Reviewed Open Access

    Mizuzo, M; Kamiya, T; Miyasaka, Y; Kim, H; Fukui, S; Ishigami, M; Suzuki, Y; Maruyama, S; Ohno, T; Hughes, T; Morgan, BP

    IMMUNOBIOLOGY   Vol. 228 ( 5 ) page: 3 - 3   2023.9

  9. IgA-dominant glomerulonephritis with DNAJB9-negative fibrillar polytypic immunoglobulin deposits in the subepithelium Open Access

    Muto, R; Maeda, K; Fukui, S; Saito, S; Kato, N; Kosugi, T; Shimizu, A; Maruyama, S

    CEN CASE REPORTS   Vol. 12 ( 3 ) page: 323 - 328   2023.8

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    Language:English   Publisher:Cen Case Reports  

    Fibrillary glomerulonephritis (FGN), a rare disease is pathologically characterized by glomerular fibril accumulation ranging from 12 to 24 nm in diameter with negative Congo red staining. Recently, the identification of DnaJ homolog subfamily B member 9 (DNAJB9) as a highly sensitive and specific marker for FGN has revolutionized diagnosis of this disease. However, few recent studies have reported DNAJB9-negative glomerulonephritis with fibrillar deposits. As such, it remains unclear whether DNAJB9-negative cases can be considered equivalent to FGN. Here, we report the case of a 70-year-old woman who developed renal impairment and nephrotic-range proteinuria. Renal biopsy and pathological examination revealed focal glomerulonephritis with fibrocellular crescents. Immunofluorescence microscopy showed IgA-dominant deposition of polytypic IgG in the glomerulus. Electron microscopy revealed hump-like subepithelial electron dense deposits with fibrils of 15–25 nm in diameter. These findings were consistent with FGN; thus, Congo red and direct fast scarlet (DFS) staining, and immunohistochemistry for DNAJB9 were performed. In addition to negative Congo red/DFS/DNAJB9 staining, laser microdissection (LMD) and liquid chromatography-tandem mass spectrometry (LC–MS/MS) resulted negative for DNAJB9, which is a highly sensitive and specific marker for FGN. The patient’s renal function further declined, prompting administration of rituximab weekly for 2 weeks, similar to the treatment for FGN. This is a unique case of IgA-dominant glomerulonephritis with DNAJB9-negative fibrillar polytypic immunoglobulin deposits in the subepithelium, unlike previous DNAJB9-negative cases. Thus, DNAJB9-negative cases diagnosed based on accurate electron microscopic evaluation must be gathered, and LMD and LC–MS/MS must be used to analyze the organized fibrillar deposits to reveal the disease entity.

    DOI: 10.1007/s13730-022-00759-2

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  10. Long-term peritoneal dialysate exposure modulates expression of membrane complement regulators in human peritoneal mesothelial cells Reviewed Open Access

    Kobayashi, K; Ozeki, T; Kim, H; Imai, M; Kojima, H; Iguchi, D; Fukui, S; Suzuki, M; Suzuki, Y; Maruyama, S; Ito, Y; Mizuno, M

    FRONTIERS IN MEDICINE   Vol. 9   page: 972592   2022.12

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    Language:English   Publisher:Frontiers in Medicine  

    The membrane complement regulators (CRegs) CD46, CD55, and CD59 are highly expressed on human peritoneal mesothelial cells. However, how mesothelial CRegs change according to the peritoneal dialysis (PD) history of patients has remained unclear. We therefore examined longitudinal changes in CRegs in primary cultured mesothelial cells from PD patients (human peritoneal mesothelial cells; HPMCs) and examined which components of PD fluid (PDF) affect CRegs in vitro. We measured levels of soluble C5b-9 in overnight-dwelling PDF in PD patients and also evaluated changes in CRegs expression on HPMCs collected from PDF using flow cytometry and polymerase chain reaction at a 1-year interval of PD therapy. We also evaluated changes in CReg expressions with stimulation by each component of PDF (glucose, lactic acid and pH) using the Met5A human mesothelial cell line. Levels of sC5b-9 in PDF decreased significantly during 1 year, while expressions of CD46 and CD59 proteins and mRNAs increased significantly in HPMCs during 1 year. Analyzing Met-5A cells, we observed that expressions of the three CRegs were increased by glucose and lactic acid in a concentration-dependent manner, but conversely that expressions of CRegs were decreased by lower pH stimulation. History of PD might influence expression of CRegs by HPMCs through properties of PDF such as glucose, lactic acid, and pH. These results suggest that mesothelial cells may alter expression of CRegs for the purpose of protecting the peritoneum and the presence of PDF might affect peritoneal homeostasis associated with the complement system.

    DOI: 10.3389/fmed.2022.972592

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  11. CD55 EXPRESSION CHANGES IN MESOTHELIAL CELLS OF PATIENTS ON PERITONEAL DIALYSIS (PD) THERAPY

    Ozeki, T; Mizuno, M; Kobayashi, K; Iguchi, D; Sei, Y; Suzuki, Y; Kojima, H; Fukui, S; Yamashita, R; Kinashi, H; Imai, M; Maruyama, S; Ito, Y

    MOLECULAR IMMUNOLOGY   Vol. 114   page: 422 - 422   2019.10

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    Language:Japanese  

    Web of Science

  12. Peritoneal expression of membrane complement regulators in peritoneal dialysis patients with fungal peritonitis

    Fukui, S; Suzuki, Y; Tawada, M; Matsukawa, Y; Imai, M; Maruyama, S; Ito, Y; Mizuno, M

    MOLECULAR IMMUNOLOGY   Vol. 102   page: 152 - 152   2018.10

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Books 1

  1. 腎疾患・透析最新の治療2017-2019

    ( Role: Contributor ,  Ⅲ.B.1ループス腎炎)

    南江堂  2017.1  ( ISBN:978-4-524-25421-7

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    Language:Japanese Book type:Textbook, survey, introduction

Presentations 3

  1. 当院CAPD患者における亜鉛欠乏と補充療法の検討

    福井聡介

    第66回日本透析医学会学術集会  2021.6.4  日本透析医学会

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    Event date: 2021.6

    Language:Japanese   Presentation type:Poster presentation  

    Venue:神奈川   Country:Japan  

  2. Complement regulator's expression in peritoneum of PD patients with fungal peritonitis. International conference

    Sosuke Fukui

    27th International Complement Workshop  2018.9.18  International Complement Society

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    Event date: 2018.9

    Language:English   Presentation type:Poster presentation  

    Venue:Santa Fe, New Mexico   Country:United States  

  3. 真菌性腹膜炎を発症したPD患者腹膜組織における補体制御因子の発現分布

    福井聡介

    第54回日本補体学会学術集会  2017.9.2  日本補体学会

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    Event date: 2017.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:福島県   Country:Japan  

KAKENHI (Grants-in-Aid for Scientific Research) 4

  1. 腹膜透析関連腹膜傷害に関与する補体系異常の解明、及び抗補体治療法の開発

    Grant number:25K11541  2025.4 - 2028.3

    科学研究費助成事業  基盤研究(C)

    福井 聡介, 水野 正司, 金 恒秀, 伊藤 恭彦

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    Authorship:Principal investigator 

    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

    腹膜透析(PD)診療において、長期PD液曝露および腹膜炎による腹膜組織傷害、それに続く腹膜機能不全、致死的な合併症である被嚢性腹膜硬化症(EPS)は、依然として最重要課題である。
    本研究では、免疫系統の一部である補体活性化第二経路の活性と制御が、上記病態の進展過程にどのように関与するか、新たに腹膜線維芽細胞の補体制御蛋白の役割にも着目し、動物モデルおよびヒト病理組織を用いて検証する。また抗補体療法の候補薬の有用性を検証する。PD合併症と補体の関与、その全体像の網羅的な解析、そして抗補体療法の臨床応用を最終目的とする。

  2. 補体H因子遺伝子改変マウスを用いた組織局所産生・細胞内補体の機能解明と治療応用

    Grant number:24K11408  2024.4 - 2027.3

    科学研究費助成事業  基盤研究(C)

    金 恒秀, 水野 正司, 福井 聡介

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    Authorship:Coinvestigator(s) 

    補体と様々な疾患の関わりが明らかになり、抗補体薬による治療により希少難治性疾患の予後が大きく改善してきたが、病態における補体の機能解明は不十分である。本研究では、2系統の補体H因子遺伝子改変マウスの①各臓器・組織局所での補体産生、②ネフロンを構成する細胞の細胞内補体を網羅的に解析しその機能を明らかにすることで、病態のより深い理解を進める。
    補体と様々な疾患の関わりが明らかになり、抗補体薬による治療により希少難治性疾患の予後が大きく改善してきたが、病態における補体の機能解明は不十分である。本研究は、組織の局所で産生される補体、そして細胞内補体(complosome)の機能に着目し、各種病態における役割を解明することが目的で、2系統の補体H因子遺伝子改変マウスの①各臓器・組織局所での補体産生、②ネフロンを構成する細胞のcomplosomeを網羅的に解析しその機能を明らかにする。
    ①については、対象をaHUSマウスの腎臓および白血球とすることとした。②はC3Gマウスのポドサイトおよび尿細管上皮細胞に限定することとした。
    マウスの繁殖の問題や研究協力者の異動などによってやや進捗が遅れている。
    推進可能な研究に絞り込んで、研究を進める。
    in vitroの実験および遺伝子解析を優先的に進める

  3. Analysis of pathogenesis associated with mutation of complement associated gene and autoantibodies in development/progression of C3 nephropathy.

    Grant number:22K08309  2022.4 - 2025.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Masashi Mizuno

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    Authorship:Coinvestigator(s) 

    To investigate pathogenesis of C3 nephropathy (C3G) and develop the treatments, we tried to generate and analyze experimental animals associated with ① genetic mutations of complement regulatory proteins or ② autoantibody production that promotes complement activation.
    ①Complement factor H (FH) mutant mice (FHm/mMo) and factor H/properdin (P) double gene-modified mice (FHm/mPKO Mo) were compared to search the pathogenesis of C3G,and severe complement deposition was observed in the glomeruli of FHm/mPKO Mo under immunofluorescence and electron microscopy, proving the importance of P.
    ②We attempted to create antibodies against C3 convertase to construct a new C3G model mouse with an autoantibody type that sustains C3 convertase (C3bBb) activity, and partly succeeded in obtaining transient proteinuria.

  4. Role of complement alternative pathway in lupus nephritis and its therapeutic application

    Grant number:21K08274  2021.4 - 2024.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Kim Hangsoo

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    Authorship:Coinvestigator(s) 

    Complement system is deeply involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis, that is expected to become a new therapeutic target.
    In this study, we investigated how each factor is involved in the pathogenesis of SLE/ lupus nephritis in spontaneous and drug-induced lupus nephritis mouse models using drugs that are long-term inhibitors of factor B, an activator of the complement alternative pathway, and loss-of-function genetically engineered mice for factor H, a regulator of the same pathway. The results to date have shown that the inhibition of factor B and the inhibition of factor B are related to the pathogenesis of lupus nephritis. Results to date show a trend toward worsening of SLE/ lupus nephritis with factor B inhibition and loss of factor H function. These results suggest that targeted complement factors and timing of treatment are important for intervention of the complement alternative pathway in SLE/ lupus nephritis.