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8 Signs And Symptoms Of An Autoimmune Disease

Medically reviewed by 
8 Signs And Symptoms Of An Autoimmune Disease

The immune system’s primary function is to defend the body from germs and other foreign substances or antigens (such as viruses, bacteria, blood cells, and tissue cells).

At the core of the immune system is a complex network of special cells and organs that, when working correctly, can identify what the self is and what is foreign. However, some immune cells can produce an autoimmune reaction if the body cannot distinguish between self and nonself. The body produces autoantibodies that attack normal cells by mistake when this happens.

Autoimmune responses are quite common and occur in many people, sometimes without causing any symptoms. John Hopkins Department of Medicine even states: “If we were to test the serum broadly enough, we would find some autoantibodies in most “healthy” individuals.” However, when this response is dysregulated and becomes chronic, an autoimmune disease can develop.

Autoimmune diseases affect around 23.5 million Americans, and recent studies indicate this number is increasing. About 25 percent of patients with one autoimmune disease tend to develop additional autoimmune diseases.

Research also shows that autoimmune disease is more commonly diagnosed in women, occurring at a rate of 2 to 1.

A Functional Medicine Approach to Autoimmune Disease involves a very detailed in take, specialty lab testing, nutritional and lifestyle adjustments.


Types of Autoimmune Disease

Some of the more well-known autoimmune diseases include:

Other autoimmune diseases are rare and can be challenging to diagnose. The average time for diagnosis of autoimmune disease is 4.5 years, and during that period, the individual typically has seen four doctors.

Autoimmune Disease Signs & Symptoms

Autoimmune diseases can be difficult to diagnose because these symptoms can also occur in other common conditions such as chronic fatigue syndrome, fibromyalgia, and Lyme disease, which are not autoimmune diseases. This overlap in symptoms makes it difficult to differentiate between autoimmune diseases and other conditions, increasing the risk of misdiagnosis or delayed diagnosis.

Symptoms of autoimmune diseases can vary in severity from being transient and mild to severe and debilitating, further complicating diagnosis. Another challenge in diagnosing autoimmune diseases is the variation in symptoms from person to person. 

For example, chronic fatigue syndrome, fibromyalgia, and Lyme disease are not autoimmune diseases, but these conditions share similarities like fatigue and muscle pain.

Different individuals may experience different symptoms, and the symptoms can also affect multiple organs and systems. For this reason, autoimmune diseases can manifest in a wide range. However, common symptoms of autoimmune disease include:

  • Fatigue
  • Joint pain and swelling
  • Dizziness
  • Muscle Pain
  • Skin problems (dry/cracked skin, rashes, blistering)
  • Abdominal pain or digestive issues
  • Recurring fever
  • Swollen glands

A functional medicine doctor or primary care physician can perform lab tests and discuss symptoms that will help identify or rule out autoimmune disease.

Autoimmune Disease Possible Causes


The autoimmune disease process is not entirely understood. Bacteria, viruses, toxins, and some drugs may trigger an autoimmune process in someone who has a genetic predisposition to develop such a disorder.

It is thought that the inflammation initiated by these agents, toxic or infections, somehow provokes the body’s autoimmune reaction.

T Lymphocytes

Regulatory T cells (also known as regulatory T lymphocytes or Tregs) regulate or suppress other cells in the immune system. In autoimmune diseases, these T cells fail to control the immune system and can exaggerate immune responses.

These attacks can affect any part of the body, weaken bodily function, and may become life-threatening. The body parts that are affected depend on the type of autoimmune disease.

Environmental Factors

Researchers suggest that lifestyle changes or environmental factors may be causing the current increase in autoimmune disease because the time frame is too short for genetic changes to occur; however, more studies are needed.

Leaky Gut

In addition, leaky gut (increased gut permeability) is present in almost every autoimmune disease in which it has been studied, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease (this includes ulcerative colitis, and  Crohn’s disease), Celiac Disease, multiple sclerosis, and type 1 diabetes.

Functional Medicine Labs to Test for Autoimmunity

Initial lab tests to screen for autoimmune markers include:


Anti-Nuclear Antibodies (ANA): A positive ANA test means autoantibodies are present, and further lab work for autoimmune disease would likely be performed.

C-Reactive Protein

C-Reactive Protein (CRP): A high CRP can be a marker for inflammation and immune activity and help screen for autoimmune disorders.

Erythrocyte Sedimentation Rate

Erythrocyte Sedimentation Rate (ESR): A fast sedimentation rate can indicate an immune disorder, as seen in high ESR.

Extractable Nuclear Antibodies

Extractable Nuclear Antibodies (ENA) The ENA panel is ordered as a follow-up after a positive ANA test if a person also has signs of an autoimmune disease. This blood test looks for several different proteins and helps to distinguish between autoimmune disorders.  

Follow Up Tests

Type 1 Diabetes

This CVD & Diabetes Prevention Essentials by BostonHeart Diagnostics measures a patient's risk of developing cardiovascular disease and diabetes.

Based on the results of this test, specific autoantibodies that are found in type 1 diabetes may be tested.

Rheumatoid Arthritis

Rheumatoid factors are proteins produced by your immune system that can attack healthy tissue in your body. High levels of rheumatoid factor in the blood are most often associated with autoimmune diseases. The Rheumatoid Arthritis Panel assesses anti-CCP3 IgG and IgA, RF, and hs-CRP to help diagnose rheumatoid arthritis.

Celiac Disease

A definitive diagnosis for celiac disease includes a small intestine (duodenum) biopsy. Because of the invasive nature of the biopsy test, other tests that are commonly used to show if the body is reacting to gluten proteins include:

Elisa LRA Gluten Panel(IgG, IgM, IgA),

Doctor's Data- Celiac and Gluten Sensitivity (IgG & IgA)

Other Autoimmune Diseases

The diagnosis of other autoimmune diseases, including multiple sclerosis, lupus, ankylosing spondylitis, inflammatory bowel disease (ulcerative colitis and Crohn’s disease), etc., are more complex and require advanced diagnostic tools such as X-rays, biopsies, MRI scans, CT scans alongside lab testing and ruling out other conditions, known as a differential diagnosis.

Comprehensive Thyroid Panel

Thyroid panel (with TPO and Tg antibodies): Thyroid peroxidase (TPO) and anti-thyroglobulin (TG) antibodies can be used to diagnose Hashimoto’s thyroiditis and Graves’ disease, two autoimmune diseases that affect the thyroid gland.

Vitamin D

Vitamin D has been shown to provide clinically beneficial effects in animal models showing proper levels may be preventive in autoimmune disorders. Supplementation is warranted if levels are below the functional range.  

Reference Range for 25-hydroxy Vitamin D

  • Standard reference range: 30-100 ng/mL
  • Functional Range: 50-80 ng/mL

Comprehensive Stool Test + Zonulin

The GI-Map with Zonulin detects a microbial imbalance, microbes contributing to illness, and indicators of digestion, absorption, inflammation, and immune function (all important factors in autoimmune disease). This test also includes Zonulin, a leaky gut marker.

Functional Medicine Treatment for Autoimmune Disease

While medication is often needed to treat autoimmune diseases, nutrition and lifestyle changes can also relieve significant symptoms.

Autoimmune Protocol (AIP)

The Autoimmune Protocol (AIP) diet is a science-based plan with medical studies supporting the benefits. The AIP diet removes foods that have compounds that may stimulate the immune system or harm the gut microbiome. It is related to the Paleo diet with stricter guidelines for certain foods that should be eliminated.

Here is a downloadable grocery list from Fullscript.

Source: Fullscript

Source: Fullscript

Two other scientifically-based autoimmune diets that follow similar principles are Wahls protocol and the Myers Way. There are some key differences, however, each diet provides instructions for the elimination phase of the diet and for transitioning to a therapeutic diet.

Elimination diets must be followed 100% of the time to be successful. Some individuals may consider doing an autoimmune diet to self-diagnose; however, using a diet protocol to determine if symptoms may be autoimmune in nature does not confirm or rule out the presence of an autoimmune disease. Instead, these individuals may do well on a 30-day paleo diet to determine if there is an improvement in symptoms while also working with a practitioner to discuss symptoms and run a series of lab tests.

Individuals diagnosed with autoimmune disease may find significant symptom relief using the AIP diet and become hesitant to reintroduce foods after the initial phase of the protocol. This diet can be quite limiting in the long term and lead to micronutrient imbalances. In general, most people will be able to reintroduce foods and can ultimately find the least restrictive diet that promotes the best symptom relief. A 5-R approach (Remove, Replace, Reinoculate, Repair, Rebalance) developed by the Institute for Functional Medicine is a helpful process to reintroduce foods and observing reactions.  

Can You Have an Autoimmune Disease with Normal Blood Work?

Autoimmune diseases can vary greatly in their presentation and severity, and it's not uncommon for individuals to have normal blood work despite experiencing symptoms.

The diagnostic process for autoimmune diseases can be complex and challenging. While blood tests are commonly used to detect specific antibodies or markers of inflammation, they may not always provide a definitive answer. This is because autoimmune diseases exist on a spectrum, and some individuals may have milder forms or be in the early stages of the disease, where blood markers may not yet be elevated.

There are several reasons why blood work may come back as normal despite the presence of an autoimmune disease. 

Firstly, autoimmune diseases can have periods of remission, where symptoms temporarily improve or disappear. During these times, blood test results may appear normal, adding to the complexity of diagnosis. 

Additionally, some autoimmune diseases may not have specific markers that can be easily identified through standard blood tests. It's essential to remember that the absence of abnormal blood work does not necessarily rule out the possibility of an autoimmune disease. 

A comprehensive evaluation, including a thorough clinical assessment and consideration of the patient's symptoms and medical history, is crucial in making an accurate diagnosis. In some cases, further testing or monitoring may be necessary to establish a definitive diagnosis.


Autoimmune disease is becoming increasingly common and can be challenging to diagnose and treat. Lab testing is an essential initial step in the process of finding and treating the root cause of symptoms quickly and effectively. “Test don’t guess” is relevant for any health concern, but this concept is critical in diagnosing autoimmune disease.

An important tool in an autoimmune treatment plan after receiving an autoimmune disease diagnosis is a therapeutic diet such as the Autoimmune Protocol. Research on the effectiveness of the AIP diet indicates that it may help control inflammation, pain, and other symptoms. For those living with autoimmune disease, it may profoundly improve the quality of life by reducing symptoms.

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The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.
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