Autoimmune synergy between lipopolysaccharides and adjuvants: A potential key to the origin of autoimmune diseases

The theory of autoimmune synergy between lipopolysaccharides (LPS) and adjuvants offers a newperspective for unraveling the enigma of autoimmune diseases. It posits that administering vaccineswith aluminum adjuvants during an active gram-negative bacterial infection can triggerautoimmune responses. This phenomenon occurs due to synergy within the lymphatic system,where the immunostimulatory effects of adjuvants enhance those of the LPS released by bacteria,disrupting the state of immune tolerance induced by LPS and other components of the bacterialouter membrane, and promoting autoimmunity. LPS exhibit dual capabilities: on one hand, they can induce partial immune tolerance; on the other,they can activate TLR4 receptors on immune cells, triggering a pro-inflammatory Th1 response.Aluminum adjuvants, designed to enhance the immunogenicity of vaccine antigens, predominantlypromote Th2 immune responses associated with antibody production. When LPS and adjuvants coincide within the lymphatic environment, a mixed hyperstimulationmay occur. The intense Th1 responses induced by LPS could lead to bacterial lysis, releasing largequantities of internal antigens that may share structural similarities with host components.Simultaneously, Th2 signals induced by the adjuvant can stimulate the production of autoantibodiesvia molecular mimicry. As a result, dysregulated immune responses may target host tissues, bothnear the site of infection and at distant locations, contributing to the development of autoimmuneresponses. The theory suggests that each autoimmune disease may be linked to a specific gram-negativebacterium through a unique mechanism of molecular mimicry, forming a clarifying map ofautoimmunity.