Autoinflammatory (Innate) versus Autoimmune (Adaptive)

Autoinflammatory (Innate) versus Autoimm

What's the Difference?

The immune system is divided into two parts: the “innate” and the “adaptive” parts.

As research into the immune system has advanced, some diseases once thought to be autoimmune (which stem from the adaptive part) are now categorized as either autoinflammatory or as having autoinflammatory components (stemming from the innate part), and some even fall somewhere in between the two.

Innate immunity means that genetic mutations are the primary cause of the immune response.

Autoinflammatory diseases stem from the innate immune system. They are characterized by episodes of apparently unprovoked inflammation (no specific environmental influence). Since they tend to have a higher genetic proponent than autoimmune diseases, they typically have early onset, meaning that they often present in childhood or early adulthood. These diseases are typically marked by rashes and spiking fevers. Autoinflammatory diseases are almost always caused by mutations in proteins that have a major role in the innate immune system.

Adaptive (acquired or specific) immunity is triggered by a learned response. Autoimmune diseases are the result of a faulty acquired immune system.

As a person's immune system encounters foreign substances (antigens), the components of acquired immunity learn the best way to attack each antigen and begin to develop a memory for that antigen. They involve some combination of genetic and environmental triggers. It is believed that the greater the genetic involvement, the earlier the disease will present; the later the onset, the higher likelihood there is a strong environmental trigger (gut or lung bacteria, smoking, etc.).


The “auto” is the commonality, which means "immune-mediated".

Both autoimmune and autoinflammatory diseases have an immune system malfunction as the underlying cause of the symptoms, but because they are triggered by different parts, the underlying causes or mechanisms of the diseases are different. This difference can affect symptom presentation, treatment options, long-term health risks, and possible complications from the systemic inflammation.

There are over 100 autoimmune and autoinflammatory diseases.

Core Diseases

IFAA (Intl Foundation for autoimmune & autoinflammatory arthritis) identifies the following as "core" autoimmune or autoinflammatory diseases that manifest usually early in life, including with the presentation of AiArthritis as an initial clinical component.  Whether a disease is autoimmune, autoinflammatory, or a combination of both is based on where it was triggered in the immune system.

  • Rheumatoid Arthritis (RA) - autoimmune disease/autoimmune arthritis

  • Psoriatic Arthritis (PsA) - autoimmune disease/autoimmune arthritis

  • Systemic Lupus Erythematosus (SLE) - autoimmune disease/autoimmune arthritis

  • Sjögren's Syndrome (SS) - autoimmune disease/autoimmune arthritis

  • Ankylosing Spondylitis (AS) - potentially a combination of autoimmune & autoinflammatory*

  • Axial Spondylitis (axSpA) - potentially a combination of autoimmune & autoinflammatory*

  • Adult Onset Still's Disease (AOSD) - autoinflammatory disease/autoinflammatory arthritis

  • Juvenile Idiopathic Arthritis (JIA) and juvenile versions of the above diseases- autoimmune disease/autoimmune arthritis

  • Systemic Juvenile Idiopathic Arthritis (sJIA) - autoinflammatory disease/autoinflammatory arthritis

  • Undifferentiated Disease


Common Symptoms of Core Diseases

The following list of early disease features were reported by at least 30% of all patients in early disease.

Autoimmune/Autoinflammatory disease features:

  1. Fatigue that is severe and unusual, not immediately corrected with rest or caffeine. ( > 95%)

  2. Flu-like symptoms, without having the flu- nausea, muscle weakness, and general malaise. ( > 50%)

  3. "Brain fog", or finding it difficult to put thoughts together. This symptom historically has been mostly associated with lupus, but it is common in the other core diseases.  ( > 30%)

  4. Fever, typically low grade with the exception of Juvenile Arthritis or Adult Onset Still's Disease, which tend to present with higher, spiking fevers. (% strongly varies per core disease)

 Arthritis features:

  1. Joint pain in at least one joint that lasts for longer than 6 weeks and cannot be explained due to injury, other condition, or medication. ( > 85%)

  2. Severe stiffness in various parts of the body, which is worse after rest or inactivity. Many patients report they suddenly feel like their bed is uncomfortable because of the severe stiffness after rest. ( > 50%)

  3. Redness and/or swelling around the joints ( > 30%)


Associated Conditions

These are some of the conditions that often can occur with these diseases:

  • Fibromyalgia (nerve condition, often misunderstood to be an autoimmune disease)

  • Dysautonomia

  • Neuropathy/Peripheral

  • Raynaud's Phenomenon

  • Eye Inflammation (uveitis/iritis/scleritis/occular)

  • Potential dental issues (such as inflammation in the gums, decay)

  • Vasculitis

  • Myositis/Polymyositis/Dermatomyositis

  • Celiac's Disease

  • Thyroidism



  1. IFAA's Early Symptoms of AiArthritis Study

  2. Undifferentiated Connective-Tissue Disease, Hildebrand, B., et al; Medscape, 2018.

  3. Autoinflammatory vs. Autoimmune

  4. Core diseases:

Photo credit: Dranoff G. Nat Rev Cancer. 2004;4:11-22