Autoimmune Diseases

Autoimmune diseases develop from an imbalance within the immune system, leading to the body failing to distinguish self from non-self¹ and, ultimately, immune cells attacking their host.² They are frequently chronic conditions that can occur at any age – depending on the disorder¹ – and can be either systemic or tissue specific.² There are almost 100 different specific diseases,¹ including type 1 diabetes – the most prevalent – rheumatoid arthritis (RA), multiple sclerosis, inflammatory bowel disease (IBD), and psoriasis.

Mechanisms of Autoimmune Diseases

Autoimmune diseases are thought to be linked to defective control of self-reactive T cells.¹ These cells are constantly being produced in the thymus of healthy individuals, and are normally eliminated before reaching maturity.^{1, 2} Their survival and proliferation in patients with autoimmune diseases contribute to tissue injury and clinical manifestation.³

Disease progression occurs through sequential phases, including initiation, propagation, and resolution.³ Initiation is typically subclinical, but propagation is characterized by inflammation due to cytokine production, epitope spreading, and an imbalance between effector T cells and regulatory T cells (T_reg cells).³ This balance can be restored during the resolution phase, but patients often suffer long term due to a persistent struggle between effector and regulatory responses.³

Treatment Strategies

Traditional immunosuppressive medications act by globally dampening the immune response, and their efficacy means that they remain the ‘gold standard’ options for treatment.¹ These agents, however, often carry severe side effects, and long-term use makes a patient highly susceptible to opportunistic infections and malignancies.¹ More targeted strategies involve immunotherapies, which focus on either inhibiting pathogenic cells, or enhancing natural pathways to suppress them.¹

Biological agents target key components of the immune system, and have transformed treatment possibilities.⁴ For example, TNF-α inhibitors have been routinely used to reduce inflammation in diseases including RA, IBD, and psoriasis.⁵ A subset of patients fail to respond or their treatment is discontinued because of adverse effects,³ leading to the research and development of novel strategies based on successful cancer immunotherapies.⁵ These methods target a narrower set of immune pathways or produce responses solely in the presence of tumor-associated antigens, thus they are now being adapted for treating autoimmune diseases.⁵

The essential role of T_reg cells in autoimmune diseases is being explored in the development of several therapeutics. The most promising involves polyclonally expanded T_reg cells that are transferred into patients with type 1 diabetes, cutaneous lupus erythematosus, or Crohn’s disease.⁶

Additional areas of interest include costimulatory blockade, antigen-specific immunotherapy, and IL-2 pathway manipulation, which all seek to help restore the balance of effector and regulatory immune function.¹