-- Proinflammatory Potential of Serum IgA Autoantibodies is Dependent on the FcAR Polymorphism --
MENLO PARK, Calif.--(BUSINESS WIRE)-- PIKAMAB, a biopharmaceutical company specializing in stratified medicine, announced today that it has secured exclusive rights to an issued U.S. patent (US 6,986,987) from the UAB Research Foundation (UABRF). This patent pertains to the discovery that the functional polymorphism (Ser/Gly248) in the cytoplasmic domain of Fc alpha receptor (FcAR) determines the proinflammatory potential of serum IgA autoantibodies through cell signaling and production of cytokines such as TNF-alpha, IL-6, and IL-1β in an allele-dependent manner.
“This IP is crucial to our strategy to develop the theragnostic products, RA TherasightTM and Lupus TherasightTM. These products will help guide the drug development process and patient treatment protocols for treating rheumatoid arthritis and systemic lupus erythematosus (SLE), respectively,” commented Vijay Ramakrishnan, Ph.D., President and CEO of PIKAMAB.
“This is an important step forward in the application of human genetic variation(s) to stratified medicine,” said Robert P. Kimberly, M.D., Professor of Medicine and Director of the Comprehensive Arthritis, Musculoskeletal and Autoimmunity Center at the University of Alabama at Birmingham. Dr. Kimberly is the inventor of this patent.
Serum IgA autoantibodies play significant roles in the pathogenesis and severity of several human inflammatory diseases including rheumatoid arthritis, SLE, lupus nephritis, and IgA nephropathy. For instance, in SLE patients of both Caucasian and African American ethnicities, the proinflammatory Gly248 allele in FcAR is enriched. “This invention assumes greater significance given that FcAR is the cognate receptor for IgA antibodies, and that Gly248 allele correlates to the severity of the disease. This FcAR polymorphism is essential to understand the early onset, severity patterns, and progression of IgA-mediated autoimmune diseases,” said Ramakrishnan.
In autoimmune disease settings, both IgA and IgG autoantibodies (and their immune complexes) play independent roles in modulating the immune responses. IgGs modulate immune responses through FcGRs. “Therefore, rational patient stratification approaches that take into consideration of the polymorphisms in FcAR and FcGRs (3A, 2A, 3B, and 2B) can provide a transformative framework to better understand the disease severity patterns and variations in treatment response in patients. Our theragnostic products provide just that framework,” explained Ramakrishnan.
About FcAR: FcAR (CD89) is the IgA-specific receptor expressed on cells of the myeloid lineage including neutrophils, monocytes, tissue macrophages, eosinophils, as well as on kidney mesangial cells and platelets. IgA-mediated immune effector responses such as phagocytosis, antibody-dependent cellular cytotoxicity, and cytokine synthesis and release are primarily mediated through FcAR. Both monomeric and dimeric IgA, and their immune complexes can bind to FcAR and activate phagocytosis and other proinflammatory responses through receptor clustering.
About IgA: Serum IgA is the second most abundant immunoglobulin after IgG. It constitutes about one-fifth of the total Ig and exists mainly in monomeric form. Serum IgA plays important roles in the pathogenesis of several human inflammatory diseases including RA, SLE, lupus nephritis, IgA nephropathy, acute myocardial infarction, and unexplained, recurrent abortions in women. Disease-specific IgA autoantibodies are produced in these patients leading to onset of proinflammatory responses. For instance, a significantly increased IgA rheumatoid factor (IgA-RF) is found in RA patients, and the patients with high levels of IgA-RF tend to be poor responders to anti-TNF-alpha biologics.
About Theragnostics: An integral component of stratified medicine, theragnostics provide therapeutic guidance in drug development and patient treatment protocols by correlating either to the mechanism of action by which the therapies work, or to the underlying mechanism of onset, progression, and the pathophysiology of the disease itself.
About PIKAMAB: An emerging industry leader in stratified medicine, PIKAMAB (pronounced Pick-a-MAb) is a biopharmaceutical company focused on developing efficacious therapeutic antibodies and theragnostic products to better treat cancers, autoimmune diseases, and inflammatory disorders. Through our proprietary patient stratification methods, we can improve the clinical trial outcomes of several antibody candidates currently in clinical development, and help achieve superior therapeutic outcomes for marketed antibody therapies. For more information, visit www.pikamab.com.
Vijay Ramakrishnan, 650-566-8344
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INDUSTRY KEYWORDS: Health Biotechnology Pharmaceutical Research Science General Health