Rethinking Spike Protein-Induced Autoimmune Disease: It is Not SLE, T1D, RA...: It Is Macrophage Dysfunction The appearance of autoimmune disease post Spike Protein exposure should be viewed as the result of macrophage dysfunction, not as the development of a discrete disease. WALTER M CHESNUT MAY 5
重新思考穗蛋白诱导的自身免疫疾病：它不是SLE，T1D，Ra ...：巨噬细胞功能障碍自身免疫性疾病的外观应被视为巨噬细胞功能障碍的结果，而不是如此 Walter M Chesnut
The possible abnormal macrophage activation in autoimmune diseases. The phagocytic function of macrophages is weakened in autoimmune diseases, which inhibits the clearance of apoptotic cells. Increased apoptotic cells promotes the production of autoimmune antigens and antibody, and further exacerbates inflammatory inflammation. In addition, macrophages promote the migration and abnormal activation of T cells including increased Th1/Th17 differentiation and downregulated Treg differentiation, and ultimately cause abnormal activation of B cells. Besides, the imbalance of M1/M2 macrophages also involved in autoimmune. Abnormal M1 macrophage activation promotes the production of proinflammatory cytokines such as IL-6, iNOS, TNF-α and IL-1β, which promote inflammation in targeted organs. Decreased M2 polarization inhibited the production of anti-inflammatory cytokines and the immune tolerance. Besides, abnormal M2 macrophage polarization also affects vascular proliferation, fibrosis in autoimmune disease such as SSc.
There have been several reports of autoimmune diseases occurring after exposure to the Spike Protein. This includes mRNA-produced Spike Protein. For example:
There is no definite data proving causality between administration of mRNA vaccines and immune-mediated inflammatory diseases (IMID).1 However, this association between autoimmunity and mRNA vaccines is an area of ongoing research and is thought to occur due to similarities between SARS-CoV-2 spike protein and human proteins.1,2 Herein, we describe a case of new-onset systemic lupus erythematosus (SLE) following the administration of a COVID-19 vaccine.
We herein report a 51-year-old Japanese woman who developed acute-onset type 1 diabetes with diabetic ketoacidosis six weeks after receiving the first dose of a COVID-19 messenger ribonucleic acid (mRNA) vaccine. Laboratory tests indicated exhaustion of endogenous insulin secretion, a positive result for insulin autoantibody, and latent thyroid autoimmunity. Human leukocyte antigen typing was homozygous for DRB109:01-DQB103:03 haplotypes. This case suggests that COVID-19 vaccination can induce type 1 diabetes in some individuals with a genetic predisposition.
Here we report a case with new-onset rheumatoid arthritis (RA) following COVID-19 vaccination. Serum concentrations not only of arthrogenic cytokines, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), but also of type I interferon (IFN) were elevated at the active phase in this case. Induction of remission by methotrexate and tocilizumab was accompanied by a marked reduction in serum concentrations of type I IFN, IL-6, and TNF-α. These results suggest that production of type I IFN, IL-6, and TNF-α induced by COVID-19 vaccination might be involved in this case with new-onset RA.
All of the above cases suggest that COVID vaccination (the Spike Protein) can induce these various autoimmune diseases. Indeed, molecular mimicry may be a culprit, yet how does the body arrive at the loss of self-tolerance which allows the induction of these autoimmune diseases? I propose we look at macrophages, which are critical in the development of autoimmune disease.
Abnormal innate immune response is a significant reason for the breakdown of autoimmune tolerance, which is closely related to the occurrence and development of autoimmune diseases (5). Macrophage is a crucial part of the innate immune system and participates in almost every biological process such as tissue homeostasis, resisting infection, repairing after infection, metabolism and inflammation, affecting the body’s development and immune response (6, 7). This review summarizes the impaired functions and abnormal macrophage activation and their roles in the pathogenesis of autoimmune diseases showed in Figure 1 (above), especially in SLE, RA, SSc and T1D. In addition, the potential value of macrophages in the treatment and prevention of autoimmune diseases is also summarized.
The reason this basis for macrophage-induced autoimmune disease must be considered is that the Spike Protein causes macrophages to act in precisely the way they do when inducing autoimmune disease not related to the Spike Protein.
Intranasal administration led to rapid lung alveolar macrophage uptake, pulmonary vascular leakage, and neutrophil recruitment and damage. When injected near the inguinal lymph node medullary, but not subcapsular macrophages, captured the protein, while scrotal injection recruited and fragmented neutrophils. Widespread endothelial and liver Kupffer cell uptake followed intravenous administration. Human peripheral blood cells B cells, neutrophils, monocytes, and myeloid dendritic cells all efficiently bound Spike protein. Exposure to the Spike protein enhanced neutrophil NETosis and augmented human macrophage TNF-α (tumor necrosis factor-α) and IL-6 production.
Murine alveolar macrophages rapidly accumulate intranasally administered SARS-CoV-2 Spike protein leading to neutrophil recruitment and damage https://elifesciences.org/articles/86764
Which explains why we are seeing so many different manifestations of autoimmune disease post Spike Protein exposure.
Cytokines such as tumor necrosis factor (TNF)-α, Interleukin (IL)-6, IL-1β, IL-12, IL-18, IL-23 and chemokines such as CXC chemokine ligands (CXCL)1, CXCL3 are secreted by macrophages, which are essential mediators and drivers of chronic inflammation and autoimmune diseases (38–40). Besides, macrophages contribute to angiogenesis by secreting proangiogenic proteases such as matrix metalloproteinases (MMP)-9 and MMP-12 (41–43). TNF-α occupies a pivotal position in RA pathogenesis. The TNF blockade reduced stromal cell activation, angiogenesis, and sustain regulatory pathways by mediating cytokine and chemokine and MMPs expression. And IL-6 signaling pathway promotes T cell activation and migration by regulating chemokine expression (44). In addition to clearing dead cells, macrophages significantly mediate wound healing and tissue homeostasis by producing anti-inflammatory molecules and tissue remodeling growth factors like IL-10 and transforming growth factor beta(TGF-β) (45). Cytokines including IL-6, IL-23, IL-10 and TGF-β all shaped Th17 cell differentiation placed at the center of autoimmune inflammation (46). IL-18 contributes to Th1/2 differentiation, participate in cytotoxic T cells (CTLs) and natural killer (NK) cells activation, and ultimately IgE production from B cells (47). Besides, tissue macrophages synthesize chemokines CXCL1/CXCL2 to increase neutrophil recruitment, which is an important early step in controlling tissue infections or injury (48). Islet-resident and islet-infiltrating macrophages can exacerbate β-cell destruction by synthesizing TNF-α, IL-12, IL-1β, and NOX2-derived ROS, which mature autoreactive CD4 and CD8 T cell effector responses (49).
We need to rethink the overwhelming onset of new autoimmune diseases. It is not that the Spike Protein induces RA or SLE, or T1D. It is that the Spike Protein causes macrophages to behave aberrantly, which induces the onset of new autoimmune disease.
I will continue to study and to search for therapeutics to help prevent these diseases from beginning. We may be able to prevent and heal many afflicted by SARS-CoV-2 and its Spike Protein by directing therapies at quelling abnormal macrophage behavior.
Please have a blessed week. Thank you, as always, for your dialogue, readership and support. 重新思考穗蛋白诱导的自身免疫疾病：它不是SLE，T1D，Ra ...：巨噬细胞功能障碍自身免疫性疾病的外观应被视为巨噬细胞功能障碍的结果，而不是如此 Walter M Chesnut 5月5日在APP中阅读，AutoImmune疾病中可能的异常巨噬细胞激活。 巨噬细胞的吞噬功能在自身免疫疾病中削弱，抑制凋亡细胞的间隙。 增加的凋亡细胞促进了自身免疫抗原和抗体的产生，进一步加剧了炎症性炎症。 此外，巨噬细胞促进T细胞的迁移和异常活化，包括增加的Th1 / Th17分化和下调的Treg分化，并最终导致B细胞的异常激活。 此外，M1 / M2巨噬细胞的不平衡也涉及自身免疫。 异常M1巨噬细胞活化促进促进促炎细胞因子的生产，例如IL-6，INOS，TNF-α和IL-1β，其促进靶向器官中的炎症。 减少的M2偏振抑制抗炎细胞因子的产生和免疫耐受性。 此外，异常的M2巨噬细胞极化也影响血管增殖，自身免疫性疾病等纤维化等SSC。 在暴露于尖刺蛋白后发生了几种关于自身免疫疾病的报道。 这包括mRNA产生的穗蛋白。 例如：MRNA疫苗和免疫介导的炎性疾病的给药之间没有明确的数据证明因果关系（IMID）。然而，自身免疫和mRNA疫苗之间的这种关联是正在进行的研究领域，并且被认为是由于之间的相似之处发生 Covid-19疫苗接种后的全身狼疮红斑狼疮新诊断：文学实验室试验表明内源性胰岛素分泌的耗尽，胰岛素自身抗体的阳性结果，以及潜在的甲状腺自身免疫。… …
Rethinking Spike Protein-Induced Autoimmune Disease: It is Not SLE, T1D, RA...: It Is Macrophage Dysfunction
The appearance of autoimmune disease post Spike Protein exposure should be viewed as the result of macrophage dysfunction, not as the development of a discrete disease.
WALTER M CHESNUT
MAY 5
重新思考穗蛋白诱导的自身免疫疾病：它不是SLE，T1D，Ra ...：巨噬细胞功能障碍自身免疫性疾病的外观应被视为巨噬细胞功能障碍的结果，而不是如此 Walter M Chesnut
https://open.substack.com/pub/wmcresearch/p/rethinking-spike-protein-induced
READ IN APP
The possible abnormal macrophage activation in autoimmune diseases. The phagocytic function of macrophages is weakened in autoimmune diseases, which inhibits the clearance of apoptotic cells. Increased apoptotic cells promotes the production of autoimmune antigens and antibody, and further exacerbates inflammatory inflammation. In addition, macrophages promote the migration and abnormal activation of T cells including increased Th1/Th17 differentiation and downregulated Treg differentiation, and ultimately cause abnormal activation of B cells. Besides, the imbalance of M1/M2 macrophages also involved in autoimmune. Abnormal M1 macrophage activation promotes the production of proinflammatory cytokines such as IL-6, iNOS, TNF-α and IL-1β, which promote inflammation in targeted organs. Decreased M2 polarization inhibited the production of anti-inflammatory cytokines and the immune tolerance. Besides, abnormal M2 macrophage polarization also affects vascular proliferation, fibrosis in autoimmune disease such as SSc.
There have been several reports of autoimmune diseases occurring after exposure to the Spike Protein. This includes mRNA-produced Spike Protein. For example:
There is no definite data proving causality between administration of mRNA vaccines and immune-mediated inflammatory diseases (IMID).1 However, this association between autoimmunity and mRNA vaccines is an area of ongoing research and is thought to occur due to similarities between SARS-CoV-2 spike protein and human proteins.1,2 Herein, we describe a case of new-onset systemic lupus erythematosus (SLE) following the administration of a COVID-19 vaccine.
New diagnosis of systemic lupus erythematosus after COVID-19 vaccination: A case report and review of literature
https://pmc.ncbi.nlm.nih.gov/articles/PMC9550275/
We herein report a 51-year-old Japanese woman who developed acute-onset type 1 diabetes with diabetic ketoacidosis six weeks after receiving the first dose of a COVID-19 messenger ribonucleic acid (mRNA) vaccine. Laboratory tests indicated exhaustion of endogenous insulin secretion, a positive result for insulin autoantibody, and latent thyroid autoimmunity. Human leukocyte antigen typing was homozygous for DRB109:01-DQB103:03 haplotypes. This case suggests that COVID-19 vaccination can induce type 1 diabetes in some individuals with a genetic predisposition.
New-onset Type 1 Diabetes after COVID-19 mRNA Vaccination
https://pmc.ncbi.nlm.nih.gov/articles/PMC9107966/
Here we report a case with new-onset rheumatoid arthritis (RA) following COVID-19 vaccination. Serum concentrations not only of arthrogenic cytokines, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), but also of type I interferon (IFN) were elevated at the active phase in this case. Induction of remission by methotrexate and tocilizumab was accompanied by a marked reduction in serum concentrations of type I IFN, IL-6, and TNF-α. These results suggest that production of type I IFN, IL-6, and TNF-α induced by COVID-19 vaccination might be involved in this case with new-onset RA.
Case Report: New-Onset Rheumatoid Arthritis Following COVID-19 Vaccination
https://pmc.ncbi.nlm.nih.gov/articles/PMC9198350/
All of the above cases suggest that COVID vaccination (the Spike Protein) can induce these various autoimmune diseases. Indeed, molecular mimicry may be a culprit, yet how does the body arrive at the loss of self-tolerance which allows the induction of these autoimmune diseases? I propose we look at macrophages, which are critical in the development of autoimmune disease.
Abnormal innate immune response is a significant reason for the breakdown of autoimmune tolerance, which is closely related to the occurrence and development of autoimmune diseases (5). Macrophage is a crucial part of the innate immune system and participates in almost every biological process such as tissue homeostasis, resisting infection, repairing after infection, metabolism and inflammation, affecting the body’s development and immune response (6, 7). This review summarizes the impaired functions and abnormal macrophage activation and their roles in the pathogenesis of autoimmune diseases showed in Figure 1 (above), especially in SLE, RA, SSc and T1D. In addition, the potential value of macrophages in the treatment and prevention of autoimmune diseases is also summarized.
Macrophage: Key player in the pathogenesis of autoimmune diseases
https://pmc.ncbi.nlm.nih.gov/articles/PMC9974150/
The reason this basis for macrophage-induced autoimmune disease must be considered is that the Spike Protein causes macrophages to act in precisely the way they do when inducing autoimmune disease not related to the Spike Protein.
Intranasal administration led to rapid lung alveolar macrophage uptake, pulmonary vascular leakage, and neutrophil recruitment and damage. When injected near the inguinal lymph node medullary, but not subcapsular macrophages, captured the protein, while scrotal injection recruited and fragmented neutrophils. Widespread endothelial and liver Kupffer cell uptake followed intravenous administration. Human peripheral blood cells B cells, neutrophils, monocytes, and myeloid dendritic cells all efficiently bound Spike protein. Exposure to the Spike protein enhanced neutrophil NETosis and augmented human macrophage TNF-α (tumor necrosis factor-α) and IL-6 production.
Murine alveolar macrophages rapidly accumulate intranasally administered SARS-CoV-2 Spike protein leading to neutrophil recruitment and damage
https://elifesciences.org/articles/86764
Which explains why we are seeing so many different manifestations of autoimmune disease post Spike Protein exposure.
Cytokines such as tumor necrosis factor (TNF)-α, Interleukin (IL)-6, IL-1β, IL-12, IL-18, IL-23 and chemokines such as CXC chemokine ligands (CXCL)1, CXCL3 are secreted by macrophages, which are essential mediators and drivers of chronic inflammation and autoimmune diseases (38–40). Besides, macrophages contribute to angiogenesis by secreting proangiogenic proteases such as matrix metalloproteinases (MMP)-9 and MMP-12 (41–43). TNF-α occupies a pivotal position in RA pathogenesis. The TNF blockade reduced stromal cell activation, angiogenesis, and sustain regulatory pathways by mediating cytokine and chemokine and MMPs expression. And IL-6 signaling pathway promotes T cell activation and migration by regulating chemokine expression (44). In addition to clearing dead cells, macrophages significantly mediate wound healing and tissue homeostasis by producing anti-inflammatory molecules and tissue remodeling growth factors like IL-10 and transforming growth factor beta(TGF-β) (45). Cytokines including IL-6, IL-23, IL-10 and TGF-β all shaped Th17 cell differentiation placed at the center of autoimmune inflammation (46). IL-18 contributes to Th1/2 differentiation, participate in cytotoxic T cells (CTLs) and natural killer (NK) cells activation, and ultimately IgE production from B cells (47). Besides, tissue macrophages synthesize chemokines CXCL1/CXCL2 to increase neutrophil recruitment, which is an important early step in controlling tissue infections or injury (48). Islet-resident and islet-infiltrating macrophages can exacerbate β-cell destruction by synthesizing TNF-α, IL-12, IL-1β, and NOX2-derived ROS, which mature autoreactive CD4 and CD8 T cell effector responses (49).
Macrophage: Key player in the pathogenesis of autoimmune diseases
https://pmc.ncbi.nlm.nih.gov/articles/PMC9974150/
We need to rethink the overwhelming onset of new autoimmune diseases. It is not that the Spike Protein induces RA or SLE, or T1D. It is that the Spike Protein causes macrophages to behave aberrantly, which induces the onset of new autoimmune disease.
I will continue to study and to search for therapeutics to help prevent these diseases from beginning. We may be able to prevent and heal many afflicted by SARS-CoV-2 and its Spike Protein by directing therapies at quelling abnormal macrophage behavior.
Please have a blessed week. Thank you, as always, for your dialogue, readership and support.
重新思考穗蛋白诱导的自身免疫疾病：它不是SLE，T1D，Ra ...：巨噬细胞功能障碍自身免疫性疾病的外观应被视为巨噬细胞功能障碍的结果，而不是如此 Walter M Chesnut 5月5日在APP中阅读，AutoImmune疾病中可能的异常巨噬细胞激活。 巨噬细胞的吞噬功能在自身免疫疾病中削弱，抑制凋亡细胞的间隙。 增加的凋亡细胞促进了自身免疫抗原和抗体的产生，进一步加剧了炎症性炎症。 此外，巨噬细胞促进T细胞的迁移和异常活化，包括增加的Th1 / Th17分化和下调的Treg分化，并最终导致B细胞的异常激活。 此外，M1 / M2巨噬细胞的不平衡也涉及自身免疫。 异常M1巨噬细胞活化促进促进促炎细胞因子的生产，例如IL-6，INOS，TNF-α和IL-1β，其促进靶向器官中的炎症。 减少的M2偏振抑制抗炎细胞因子的产生和免疫耐受性。 此外，异常的M2巨噬细胞极化也影响血管增殖，自身免疫性疾病等纤维化等SSC。 在暴露于尖刺蛋白后发生了几种关于自身免疫疾病的报道。 这包括mRNA产生的穗蛋白。 例如：MRNA疫苗和免疫介导的炎性疾病的给药之间没有明确的数据证明因果关系（IMID）。然而，自身免疫和mRNA疫苗之间的这种关联是正在进行的研究领域，并且被认为是由于之间的相似之处发生 Covid-19疫苗接种后的全身狼疮红斑狼疮新诊断：文学实验室试验表明内源性胰岛素分泌的耗尽，胰岛素自身抗体的阳性结果，以及潜在的甲状腺自身免疫。… …