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International journal of molecular sciences
Nov 06, 2023;24 (21):

Study on the Treatment of ITP Mice with IVIG Sourced from Distinct Sex-Special Plasma (DSP-IVIG).

Wei Zhang, Xin Yuan, Zongkui Wang, Jixuan Xu, Shengliang Ye, Peng Jiang, Xi Du, Fengjuan Liu, Fangzhao Lin, Rong Zhang, Li Ma, Changqing Li
Author Information
  1. Wei Zhang: Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China.
  2. Xin Yuan: Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China.
  3. Zongkui Wang: Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China. ORCID
  4. Jixuan Xu: Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China.
  5. Shengliang Ye: Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China. ORCID
  6. Peng Jiang: Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China.
  7. Xi Du: Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China.
  8. Fengjuan Liu: Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China.
  9. Fangzhao Lin: Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China.
  10. Rong Zhang: Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China. ORCID
  11. Li Ma: Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China.
  12. Changqing Li: Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China.
PMID: 37958975 DOI: 10.3390/ijms242115993

Abstract

Intravenous immunoglobulin (IVIG) is a first-line drug prepared from human plasma for the treatment of autoimmune diseases (AIDs), especially immune thrombocytopenia (ITP). Significant differences exist in protein types and expression levels between male and female plasma, and the prevalence of autoimmune diseases varies between sexes. The present study seeks to explore potential variations in IVIG sourced from distinct sex-specific plasma (DSP-IVIG), including IVIG sourced from female plasma (F-IVIG), IVIG sourced from male plasma (M-IVIG), and IVIG sourced from a blend of male and female plasma (Mix-IVIG). To address this question, we used an ITP mouse model and a monocyte-macrophage inflammation model treated with DSP IVIG. The analysis of proteomics in mice suggested that the pathogenesis and treatment of ITP may involve FcγRs mediated phagocytosis, apoptosis, Th17, cytokines, chemokines, and more. Key indicators, including the mouse spleen index, CD16 macrophages, M1, M2, IL-6, IL-27, and IL-13, all indicated that the efficacy in improving ITP was highest for M-IVIG. Subsequent cell experiments revealed that M-IVIG exhibited a more potent ability to inhibit monocyte phagocytosis. It induced more necrotic M2 cells and fewer viable M2, resulting in weaker M2 phagocytosis. M-IVIG also demonstrated superiority in the downregulation of surface makers CD36, CD68, and CD16 on M1 macrophages, a weaker capacity to activate complement, and a stronger binding ability to FcγRs on the THP-1 surface. In summary, DSP-IVIG effectively mitigated inflammation in ITP mice and monocytes and macrophages. However, M-IVIG exhibited advantages in improving the spleen index, regulating the number and typing of M1 and M2 macrophages, and inhibiting macrophage-mediated inflammation compared to F-IVIG and Mix-IVIG.

Keywords

IVIG sourced from distinct sex-specific plasma (DSP-IVIG) immune thrombocytopenia intravenous immunoglobulin macrophages proteomics

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Grants

  1. 2023NSFSC0714, 2023ZHCG0066 and 2022YFS0010/Department of Science and Technology of Sichuan Province
  2. CIFMS, 2021-I2M-1-042/CAMS Innovation Fund for Medical Sciences
  3. Q22009/Scientific Research Project of Sichuan Medical Association

MeSH Term

Male
Female
Humans
Animals
Mice
Immunoglobulins, Intravenous
Purpura, Thrombocytopenic, Idiopathic
Thrombocytopenia
Cytokines
Inflammation

Chemicals

Immunoglobulins, Intravenous
Cytokines
Journal Article

Word Cloud

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