Autoinflammatory disease

Autoinflammatory Disease

Autoinflammatory diseases are a group of disorders characterized by recurrent episodes of systemic inflammation, often without the presence of high-titer autoantibodies or antigen-specific T cells. These diseases are primarily caused by genetic mutations that affect the innate immune system, leading to inappropriate activation and inflammation.

Overview

Autoinflammatory diseases are distinct from autoimmune diseases, which involve the adaptive immune system. While autoimmune diseases are characterized by the body's immune system attacking its own tissues, autoinflammatory diseases are due to dysregulation of the innate immune system, leading to spontaneous inflammation.

Pathophysiology

The pathophysiology of autoinflammatory diseases involves mutations in genes that regulate the innate immune response. These mutations often affect proteins involved in the inflammasome pathway, leading to excessive production of pro-inflammatory cytokines such as interleukin-1 (IL-1).

Inflammasomes

Inflammasomes are multiprotein complexes that play a critical role in the activation of inflammatory responses. They detect pathogenic microorganisms and stressors, leading to the activation of caspase-1, which in turn processes pro-inflammatory cytokines like IL-1β and IL-18 into their active forms.

Common Autoinflammatory Diseases

Familial Mediterranean Fever (FMF)

Familial Mediterranean Fever is the most common autoinflammatory disease, caused by mutations in the MEFV gene, which encodes the protein pyrin. It is characterized by recurrent episodes of fever and serositis, including peritonitis, pleuritis, and arthritis.

Cryopyrin-Associated Periodic Syndromes (CAPS)

CAPS is a group of disorders caused by mutations in the NLRP3 gene, which encodes cryopyrin. This group includes:

• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Chronic Infantile Neurological Cutaneous and Articular Syndrome (CINCA), also known as Neonatal-Onset Multisystem Inflammatory Disease (NOMID)

Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)

TRAPS is caused by mutations in the TNFRSF1A gene, leading to prolonged inflammatory episodes characterized by fever, abdominal pain, and myalgia.

Diagnosis

Diagnosis of autoinflammatory diseases is based on clinical presentation, family history, and genetic testing. Laboratory tests may show elevated inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

Treatment

Treatment strategies for autoinflammatory diseases focus on controlling inflammation and preventing complications. Common treatments include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Colchicine, particularly for FMF
• Interleukin-1 inhibitors such as anakinra and canakinumab

Research and Future Directions

Ongoing research aims to better understand the genetic and molecular mechanisms underlying autoinflammatory diseases, with the goal of developing more targeted therapies. Advances in genomics and biologics are promising areas of development.

See Also

• Autoimmune disease
• Inflammasome
• Cytokine

References

• Kastner, D. L., Aksentijevich, I., & Goldbach-Mansky, R. (2010). Autoinflammatory disease reloaded: a clinical perspective. Cell, 140(6), 784-790.
• Masters, S. L., Simon, A., Aksentijevich, I., & Kastner, D. L. (2009). Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annual Review of Immunology, 27, 621-668.