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.

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.