Cells collected on D4
Cells collected on D4. and IVIG sourced from a blend of male and female plasma (Mix-IVIG). To address RO462005 this question, we used an ITP mouse model and a monocyteCmacrophage inflammation model treated with DSP IVIG. The analysis of proteomics in mice suggested that the pathogenesis and treatment of ITP may involve FcRs mediated phagocytosis, RO462005 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 FcRs 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: intravenous immunoglobulin, IVIG sourced from distinct sex-specific plasma (DSP-IVIG), immune thrombocytopenia, proteomics, macrophages 1. Introduction Intravenous immunoglobulin (IVIG) is a mixture of immunoglobulins extracted from the pooled plasma of thousands of healthy donors. The utilization of plasma from multiple donors contributes to the broad spectrum and specificity of IVIG antibodies. IVIG is currently employed in more NFKBIA than 100 clinical indications, including the treatment of primary immunodeficiency disease (PID), secondary immunodeficiency syndrome (SID), autoimmune diseases (AIDs), etc. [1,2,3]. The main component of IVIG is immunoglobulin G (IgG). Following papain hydrolysis, classical IgG antibody consists of one molecule of fragment crystallizable (Fc) and two molecules of fragment of antigen binding (Fab) fragments [4,5]. AIDs arise from the bodys immune response against its own components, resulting in tissue damage and organ dysfunction. One such AID is ITP, characterized by platelet destruction mediated by autoantibodies [6]. The existing literature has identified numerous factors associated with the course of ITP, including macrophages, T helper cells (Th1, Th2, Th17) [7], cytotoxic RO462005 T lymphocytes (CTL), regulatory T cells (Treg), T follicular helper cells (Tfh) [8,9,10], dendritic cells (DCs), megakaryocyte (MK), B cells, plasma cells, regulatory B cells (Breg) [11,12,13,14]. Additionally, internal homeostasis disorders of bone marrow (BM) have been implicated in ITP [8]. In clinical practice, IVIG serves as a first-line treatment drug for ITP [15,16,17,18,19], and the use of IVIG in the clinical treatment of severe ITP requires high-dose infusion [20,21]. IVIG production involves raw plasma, and it is used to treat various AIDs. But how does sex relate to these components? Silliman, C. C. and others found that female plasma expresses more pregnancy zone protein, coagulation factor V, complement factor H, C4B, etc., than male plasma, while male plasma expressed more Fc binding protein, transgelin-2, etc., than female plasma [22]. Moreover, the intervention of different sexual plasma in diseases also varied; for example, transfusion-related acute lung injury (TRALI), which is a high mortality adverse reaction caused by blood transfusion [23]. In 2006, American scholars suggested that pregnant women should be excluded from fresh frozen plasma (FFP) and platelet apheresis. The American Red Cross began to give priority to the distribution of plasma from male donors in 2007, and then the number of TRALI cases decreased by 80% [24]. Similarly, in the UK, starting from the end of 2003, 80% to 90% of FFP, platelets, and plasma in UK hospitals were sourced from male donors. It was found that after 2003 in the UK, the reports of TRALI showed a decreasing trend year by year [25]. In addition, Desai et al. found that the prevalence of AIDs varied between males and females [26]. For example, women were more likely to RO462005 experience multiple systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), and Sj?grens syndrome (SS) than men. These differences may arise from a multitude of factors, including susceptibility related to sexual target organs, reproductive function, hormone levels, environmental factors, immune responses, and genetic factors [27]. IVIG undergoes a series of standardized tests after preparation, including ensuring an IgG content of over 95%, distribution of IgG subclasses, Fc function, prekallikrein activator (PKA) level, hemagglutinin, and more [28]..