From the Guidelines
Autoimmune conditions are primarily caused by a combination of genetic predisposition, environmental triggers, and failure of immune tolerance mechanisms, leading to a self-directed immune response that mistakenly attacks the body's own tissues and organs. Several key mechanisms contribute to this self-directed immune response, including genetic factors such as certain HLA types and gene variants that predispose individuals to specific autoimmune diseases 1. Environmental triggers, such as infections, medications, and toxins, can initiate autoimmunity in genetically susceptible individuals through molecular mimicry, where immune cells confuse self-proteins with pathogen components.
The failure of immune tolerance mechanisms is central to autoimmunity, occurring when T and B cell selection processes that normally eliminate self-reactive cells become defective 1. Regulatory T cell dysfunction further compounds this problem by reducing immune system suppression. Epitope spreading, where immune responses expand to target additional self-antigens beyond the initial trigger, contributes to disease progression. Hormonal influences explain the higher prevalence of autoimmune conditions in women. Dysregulation of cytokines, immune signaling molecules, creates inflammatory environments that perpetuate autoimmune reactions.
Some of the key mechanisms involved in autoimmune conditions include:
- Genetic predisposition: certain HLA types and gene variants predispose individuals to specific autoimmune diseases 1
- Environmental triggers: infections, medications, and toxins can initiate autoimmunity in genetically susceptible individuals through molecular mimicry 1
- Failure of immune tolerance mechanisms: T and B cell selection processes that normally eliminate self-reactive cells become defective 1
- Regulatory T cell dysfunction: reduces immune system suppression 1
- Epitope spreading: immune responses expand to target additional self-antigens beyond the initial trigger 1
- Hormonal influences: explain the higher prevalence of autoimmune conditions in women 1
- Dysregulation of cytokines: creates inflammatory environments that perpetuate autoimmune reactions 1
These mechanisms often work in combination, creating a complex pathophysiology that varies between different autoimmune conditions. For example, in type 1 diabetes, autoimmune destruction of the pancreatic b-cells is caused by a combination of genetic and environmental factors, and is characterized by the presence of autoantibodies and a progressive loss of b-cell function 1.
From the FDA Drug Label
B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis. In this setting, B cells may be acting at multiple sites in the autoimmune/inflammatory process, including through production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and/or proinflammatory cytokine production.
The mechanisms that lead to autoimmune mediated conditions, as mentioned in the context of rheumatoid arthritis, include:
- Production of rheumatoid factor (RF) and other autoantibodies
- Antigen presentation
- T-cell activation
- Proinflammatory cytokine production 2
From the Research
Mechanisms of Autoimmune Mediated Conditions
The mechanisms leading to autoimmune mediated conditions are complex and involve the interplay of various factors, including:
- Genetic predisposition, as most autoimmune diseases result from the complex interplay between environmental and genetic factors 3
- Dysfunction of the acquired immune system, leading to the immune system attacking healthy cells 4
- Abnormal antibodies, known as autoantibodies, which are generated by pathogenic B cells and target an individual's own tissue 5
- Imbalance in the innate and adaptive immune systems, involving cytokines and chemokines mediating extracellular and paracrine effects 6
Key Factors Contributing to Autoimmune Diseases
Some key factors contributing to autoimmune diseases include:
- Environmental factors, which can trigger the onset of autoimmune diseases in genetically predisposed individuals 3
- Hormonal impacts, which can explain why autoimmune diseases occur more frequently in women than men 5
- Inflammatory cascade, which is mediated by multifaceted processes involving various cell types and molecules 6
Treatment and Management
Treatment and management of autoimmune diseases aim to:
- Decrease inflammation and minimize symptoms 4
- Lessen the potential for relapse 4
- Limit inflammation and immune responses to antigens using immunosuppressive agents 6, 7
- Target specific molecules and pathways involved in the immune response, providing alternatives to cytotoxic therapy in immune-mediated diseases 7