Autoantibodies are antibodies that react with self-antigens, antigens that originate within the body. This is called autoreactivity. Autoantibodies may react with self-antigens present in all cell types, such as chromatin and centromeres, or they may react to a specific cell type such as thyroglobulin cells in the thyroid gland. Antigens may be comprised of proteins, nucleic acids, carbohydrates, lipids, or combinations of these molecules.
Normally autoreactivity is prevented during the development and maturation of antibody-producing B cells in the bone marrow and spleen. Immature B cells that express receptors that recognize self-antigens are depleted or silenced. T lymphocytes and the elimination of strongly self-reactive T cell receptors are also a part of establishing tolerance of self. Leakiness in these central or peripheral tolerance mechanisms results in the presence of autoantibodies in the serum.
Autoreactive B cells and autoantibodies are frequently observed in healthy individuals and are not necessarily pathogenic. In a small proportion of these individuals, this leads to autoimmune diseases such as rheumatoid arthritis or Graves’ disease. Autoantibodies can alter or block receptor stimulation, neural transmission, and cell signaling and cause microthrombosis, cell lysis, neutrophil activation, and inflammation. Autoimmune conditions and cancer share a repertoire of autoantibodies. Autoantibodies associated with Sjögren's syndrome, systemic sclerosis, and systemic lupus erythematosus (SLE) are found to be circulating in 30% of cancer patients.
Common treatment of autoimmune disease is systemic immunosuppression, such as with corticosteroids. The immunosuppressant Rituximab is a monoclonal antibody originally used to treat lymphoma, but used to treat autoimmune diseases. Rituximab removes B lymphocytes from circulation through binding to the CD20 receptor. The detection and characterization of types of autoantibodies present in serum are used for disease diagnosis, for research on disease mechanisms, and for the discovery of treatment targets.
For pemphigus vulgaris, an autoimmune disease characterized by skin blistering, autoantigen-based chimeric immunoreceptors were used to direct T cells to kill autoreactive B lymphocytes in a mouse model for the disease. In pemphigus vulgaris, that therapeutic target is pathogenic memory B cells which express receptors to keratinocyte adhesion protein Dsg3. Researchers used chimeric autoantibody receptor (CAAR) technology, which is adapted from chimeric antigen receptor (CAR) technology used in cancer therapy.
Autoantibodies are associated with chronic pain through their promotion of tissue damage and inflammatory reactions. There are also potential mechanisms by which autoantibodies cause pain through non-inflammatory mechanisms, such as targeting sensory neurons directly or indirectly. Antibodies can directly activate sensory neurons through their constant (Fc) or antigen-binding (Fab) regions. Autoantibodies purified from patients with rheumatoid arthritis (RA) and complex regional pain syndrome (CRPS) were found to induce pain-like behavior when injected into mice through indirect, non-inflammatory sensitization of pain fibers. Pathogenic autoantibodies that target neuronal surface antigens (NSAbs) modulate the activity and properties of their neuronal targets; such autoantibodies targeting the voltage-gated potassium channel complex (VGKCC) have been found in patients with peripheral nerve hyperexcitability (PNH) and Morvan’s syndrome.
Atreca—product ATRC-101 is a monoclonal antibody based on discovery of a patient-derived autoantibody that targets ribonucleoprotein complex, a treatment for solid tumors
Biogen—aducanumab for treatment of Alzheimer's was originally derived from healthy donors that avoided Alzheimer's disease. The antibody binds aggregated forms of β-amyloid peptide Aβ β-amyloid peptide (original company Neurimmune in Schlieren, Switzerland)
Cabaletta Bio—MuSK chimeric autoantibody receptor (CAAR) T cells as an antigen-specific cellular immunotherapy to treat the chronic autoimmune disease Muscle-Specific Tyrosine Kinase Myasthenia Gravis. The therapy is designed to direct patient T cells to kill B cells expressing disease-causing autoantibodies on their surface. (https://apnews.com/press-release/globenewswire-mobile/ca1e4d07b0cfdcb2398701b3aec05d63)
Catalent Biologics partnered with Grid Therapeutics—human-derived targeted immunotherapy for solid tumor cancers based on an antibody identified in patients with early stage lung cancer that disables complement factor H (CFH) a protein that protects cancer cells from immune system attack
ImmunoQure—Autoantibodies occurring in patients with an ultra-rare type of autoimmune disorder called autoimmune polyendocrine syndrome type 1 (APS1 or APECED) are thought to have benefits, such as anti-inflammatory properties and potential to be used as therapeutic agents or as a basis for designing immunotherapies to treat autoimmune diseases
A number of autoantibody teams have been acquired by venture capital groups or larger biopharmaceutical companies. These companies range from self-operational wholly-owned subsidiaries to past companies that have been completely assimilated into the parent organization.
These companies operate themselves and have not been purchased by parent organizations. They range from small personal-owned companies to public incorporations and limited liabilities corporations, although the majority are smaller businesses found in the US and Europe.
