Autoimmune Viral Trio PANEL

This mimicry could cause an immune reaction in which antibodies produced against viral antigens may also attack the body’s own tissues. Subsequent viral infections are thought to cause exacerbation of the disease by further activation of the immune response against viral and self-antigens.

Three viruses, in particular, have been identified as the major players and contributors towards inflamm- ation and autoimmune disorders: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6).

SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-CoV-2)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for coronavirus disease 2019 (COVID-19), the disease that became a modern pandemic infecting and killing millions of people worldwide. A significant heterogeneity in immune response against pathogens, in particular, SARS-CoV-2, exists among the general population. In fact, three completely different immunotypes were reported in patients hospitalized with COVID-19:

1. With robust CD4 and highly activated CD8+ T cells, and high level of antibody production.
2. With robust CD8+ T cells, but less activated T cells and lower level of antibody production.
3. With minimal lymphocyte activation and response to SARS-CoV-2, and possibly lack of antibody production.

This heterogeneity in immune response to SARS-CoV-2 may result in different responses to the virus as well as to vaccine antigens.

Detection of low or high levels of IgG antibody made against SARS-CoV-2 spike protein and nucleoprotein in the blood is the most practical approach for the assessment of an individual’s immune response to SARS-CoV-2, indicating recent or prior response to SARS-CoV-2 antigens. Elevation in IgG anti-SARS-CoV-2 above the reference ranges indicates exposure to SARS-CoV-2 or vaccination.

A low level of IgG against SARS-CoV-2 antigens after infection with COVID-19 or vaccination may indicate a lack of immune response to the viral antigens.

Cumulative evidence indicates that SARS-CoV-2 has the ability to induce hyper-stimulation of the immune system, therefore leading to the synthesis of multiple autoantibodies, which may trigger possibly pre-existing autoimmune diseases. These autoimmune responses may develop through two principal mechanisms: 1) the ability of the virus to induce hyper-stimulation of the immune system; 2) the molecular resemblance between the virus and self-components of the host. Due to its great similarity to human tissue, SARS-CoV-2 has also been called the autoimmune virus. The virus and its disease, COVID-19, have been associated with various autoimmune disorders including type 1 diabetes, Graves’ disease, autoimmune hemolytic anemia, polyneuritis cranialis, post orthostatic tachycardia syndrome, systemic lupus erythematosus, antiphospholipid syndrome, Guillain-Barré syndrome, rheumatoid arthritis, immune thrombocytopenic purpura, Miller Fisher syndrome, Kawasaki disease, and vasculitis.

EPSTEIN-BARR VIRUS (EBV)

Epstein-Barr virus (EBV) or herpes type 4 is a ubiquitous human virus that infects almost all humans during their lifetime. EBV in children and in some adults causes the infection called mononucleosis, which results in the production first of IgM and then IgG antibodies against viral capsid antigen (EBV-VCA). Following the acute phase, the virus persists mainly in the epithelial cells and B lymphocytes for the rest of the afflicted person’s life.

Under a variety of conditions that negatively affect the immune system, reactivation of EBV can occur, resulting in the expression of early antigen (EBV-EA) and the production of antibody against EA.

Epstein-Barr nuclear antigen (EBNA) is another antigen that induces the production and proliferation of B cells, which are responsible for the generation of antibodies in the body. This is why EBV is associated with different proliferative and autoimmune disorders, including lymphomas, rheumatoid arthritis, Graves’ disease, Hashimoto’s disease, lupus, multiple sclerosis (MS), inflammatory bowel disease, celiac disease, autoimmune liver disease, type 1 diabetes, polyneuropathy and Sjögren’s syndrome. The elevation of IgM antibody against EBV antigens may indicate ongoing viral infection or viral reactivation. In the case of very high levels of IgG antibody against EBV antigens, if these antigens manage to bind to self-tissue antigens due to cross-reactivity, the result may be autoimmune reactivity.

HUMAN HERPESVIRUS TYPE 6 (HHV-6)

Human herpesvirus type 6 (HHV-6) type A and type B are neurotrophic viruses that cause the common childhood disease known as roseola. By age 3, 90-100% of humans are infected by HHV-6 via the nasal cavity. The olfactory pathway is the major route of entry into the nervous system. The virus persists in a variety of cells, including glial cells, for the rest of the afflicted person’s life. Immune reaction against HHV-6 results in the production of both IgM and IgG antibodies.

HHV-6 A reactivation documented by IgM antibody elevation has been shown to alter mitochondrial fragmentation in patients with chronic fatigue syndrome or myalgic encephalomyelitis. HHV-6 B is linked to several autoimmune and neurodegenerative disorders via molecular mimicry and other mechanisms. These include MS, Guillain-Barré syndrome, lupus, Sjögren’s syndrome, Hashimoto’s thyroiditis, Alzheimer’s disease, Parkinson’s disease, collagen vascular disease, epilepsy, and encephalitis, including myalgic encephalomyelitis (ME/CFS). In the presence of significant elevations in IgG antibody against antigens of HHV-6 type A or type B, the binding of these IgG antibodies to human tissue antigens may result in autoimmune reactivity.

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