10 Most Commonly Ordered Functional Medicine Autoimmune Tests

Autoimmune conditions are some of the most challenging and complex health issues today. With the immune system mistakenly attacking healthy tissues, these disorders often involve chronic inflammation, pain, and fatigue. 

Functional medicine takes a personalized approach to understanding and treating autoimmune diseases by ordering comprehensive lab tests that go beyond traditional methods, to aid in diagnosing and individualizing a patient’s treatments. 

These tests provide deeper insights into immune function, inflammation, and genetic predispositions, helping both patients and practitioners create more tailored treatment plans.

In this article, we will explore the most commonly ordered autoimmune labs by functional medicine practitioners and discuss why and when these tests should be considered.

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1. Comprehensive Autoimmune Panel (Including CRP, ESR, and ANA with Reflex Panel)

A comprehensive autoimmune panel is often the first step when autoimmune disease is suspected. This panel includes tests that assess systemic inflammation and the presence of autoimmune antibodies, offering a broad look at the body's immune response and assisting in a clear diagnosis.

What It Includes

The comprehensive panel typically includes tests like the Antinuclear Antibody (ANA) test with reflex, C-reactive Protein (CRP), and Erythrocyte Sedimentation Rate (ESR), among others.

• Antinuclear Antibody (ANA) Test with Reflex: detects antibodies that attack the nuclei of cells, often indicating autoimmune diseases like lupus. If ANA is positive, reflex testing further identifies specific antibodies present to clarify a diagnosis.

• C-reactive Protein (CRP): measures the level of CRP in the blood, a marker of inflammation. Elevated CRP suggests ongoing inflammation, common in autoimmune diseases.

• Erythrocyte Sedimentation Rate (ESR): measures how quickly red blood cells settle at the bottom of a test tube, which indicates the presence of inflammation in the body. 

Why It’s Ordered 

These tests are often ordered to screen for autoimmune diseases such as lupus, rheumatoid arthritis (RA), and Sjögren's syndrome. They help identify underlying autoimmune activity and the severity of inflammation.

What It Reveals

• ANA with reflex panel: the ANA test looks for antibodies that attack the nucleus of cells. A positive result initiates reflex testing for specific antibodies associated with lupus, mixed connective tissue disease, and other conditions to aid in diagnosis.

• CRP and ESR: both CRP and ESR are general markers of inflammation. CRP rises quickly during acute inflammation or infection, while ESR increases more gradually, reflecting chronic inflammation and ongoing disease activity. Together, these general inflammatory markers can provide a more complete picture of disease progression. 

By including multiple tests, this panel provides a more complete picture of how the immune system is functioning, helping to identify or rule out multiple autoimmune disorders.

2. Anti-DsDNA Antibody Test

The Anti-DsDNA Antibody Test is highly specific for diagnosing lupus (Systemic Lupus Erythematosus, or SLE).

What It Is

Anti-DsDNA tests detect antibodies against double-stranded DNA. These antibodies are strongly associated with lupus and can also indicate disease severity.

Why It’s Ordered 

This test is primarily used to diagnose lupus patients but can also help monitor disease progression or response to treatment. In combination with other tests, it can differentiate lupus from other autoimmune conditions.

What It Reveals

A high level of anti-DsDNA antibodies is a key indicator of lupus and is often present during disease flare-ups and in lupus nephritis (kidney inflammation and damage, commonly seen in lupus). This makes the test useful for both diagnosis and ongoing disease management.

3. Rheumatoid Factor (RF) and Anti-CCP (Cyclic Citrullinated Peptide)

These two tests are used to diagnose and differentiate rheumatoid arthritis (RA) from other autoimmune conditions.

What They Are

• Rheumatoid Factor (RF): a protein that can attack healthy tissues, often present in RA. Rheumatoid factor is found in various autoimmune and non-autoimmune conditions, so it must be combined with anti-cyclic citrullinated peptide to improve diagnostic accuracy for rheumatoid arthritis.

• Anti-CCP: antibodies against citrullinated peptides, which are highly specific to RA.

Why They’re Ordered

These tests are ordered when RA is suspected, especially in cases of joint pain and inflammation that haven’t been explained by other conditions.

What They Reveal

A positive RF test may suggest RA but can also appear in other conditions.

Anti-CCP is more specific and is often used to confirm an RA diagnosis. A positive anti-CCP result usually points to a more severe form of RA and can help predict disease progression.

Together, these tests offer valuable insights into the diagnosis and management of rheumatoid arthritis.

4. Anti-Thyroid Antibodies

Autoimmune thyroid disease is increasingly common and often co-occurs with other autoimmune conditions. 

What They Are

• Thyroid Peroxidase (TPO) Antibodies: these antibodies target thyroid peroxidase, an enzyme essential for producing thyroid hormones. They are commonly present in autoimmune thyroid diseases like Hashimoto's thyroiditis and Graves' disease.

• Thyroglobulin (TG) Antibodies: these antibodies attack thyroglobulin, a protein used by the thyroid gland to produce hormones. TG antibodies are frequently elevated in Hashimoto's thyroiditis.

• Thyroid Stimulating Immunoglobulin (TSI): these antibodies mimic the action of Thyroid Stimulating Hormone (TSH), stimulating the thyroid gland to produce excess thyroid hormone. They are primarily associated with Graves' disease.

Why It’s Ordered

Functional medicine practitioners order tests for these antibodies when patients exhibit symptoms of thyroid dysfunction such as fatigue, weight changes, or hair loss. 

A functional medicine practitioner might also consider anti-thyroid antibody testing in patients with other diagnosed autoimmune conditions to assess for the potential co-occurrence of autoimmune thyroid diseases.

The presence of these antibodies helps diagnose autoimmune thyroid conditions like Hashimoto's thyroiditis (hypothyroidism) or Graves' disease (hyperthyroidism), which involve immune system attacks on the thyroid.

What It Reveals

• TPO Antibodies: elevated levels indicate an autoimmune attack on the thyroid, commonly leading to hypothyroidism in Hashimoto's or hyperthyroidism in Graves'.

• TG Antibodies: high TG antibody levels suggest thyroid tissue damage due to autoimmune conditions, especially Hashimoto's.

• TSI Antibodies: high TSI levels reveal overactive thyroid function, which leads to hyperthyroidism in Graves' disease, often resulting in symptoms like rapid heart rate and weight loss.

5. Celiac Panel Tissue Transglutaminase (tTG) IgA/IgG, Anti-Endomysial IgA, Deamidated Gliadin Peptide IgA/IgG)

Celiac disease is an autoimmune condition triggered by the ingestion of gluten. The Celiac Panel tests for antibodies that indicate the immune system is reacting to gluten.

What It Is

The celiac panel includes tests for Tissue Transglutaminase (tTG) IgA/IgG, Deamidated Gliadin Peptide IgA/IgG, total IgA, and Anti-Endomysial IgA antibodies. 

These tests assess the immune system's response to gluten and help diagnose celiac disease.

Why It’s Ordered

Medical providers use this panel when celiac disease or gluten sensitivity is suspected. Common reasons for ordering the panel include chronic digestive issues, fatigue, unexplained nutrient deficiencies, and other symptoms potentially linked to gluten intolerance or malabsorption.

What It Reveals

• tTG IgA/IgG: a hallmark indicator of celiac disease, signaling an autoimmune response against tissue transglutaminase in the small intestine. This is a first-line test for celiac disease. IgG testing may be done alongside IgA tests to diagnose celiac disease in people with IgA deficiency.

• Deamidated Gliadin Peptide IgA/IgG tests: these tests detect immune reactions to gluten proteins, indicating sensitivity or intolerance to gluten. They are particularly valuable in detecting celiac disease in children and in those with IgA deficiency.

• Anti-Endomysial IgA antibodies: Highly specific for celiac disease, these antibodies target the endomysium, a part of the small intestine’s connective tissue, and are a strong marker of intestinal damage.

• Total IgA: ensures the accuracy of the other antibody tests, as IgA deficiency (which is more common in celiac disease patients than in the general population) could lead to false-negative results.

Elevated antibody levels suggest that the body is mounting an autoimmune response to gluten, damaging the small intestine and impairing nutrient absorption.

6. HLA-B27 Genetic Test

The HLA-B27 test is a genetic marker that predisposes individuals to certain autoimmune conditions, most notably ankylosing spondylitis, other inflammatory joint conditions, and inflammation of the eye. It is associated with autoimmunity.

What It Is 

This test identifies the presence of the HLA-B27 gene, which is linked to inflammatory autoimmune diseases.

Why It’s Ordered

HLA-B27 genetic testing is ordered to support the diagnosis of inflammatory conditions like ankylosing spondylitis, reactive arthritis, and uveitis (inflammation of the middle part of the eye, which often requires prompt medical treatment to prevent complications). 

This is often ordered in younger patients with symptoms such as inflammatory back pain or eye inflammation. While a positive result increases the likelihood of these diseases, many people with HLA-B27 never develop them.

What It Reveals

A positive HLA-B27 test doesn’t necessarily confirm disease but indicates an increased risk for conditions like ankylosing spondylitis or reactive arthritis.

7. MTHFR Gene Mutation Test

The MTHFR gene mutation test is often used to evaluate methylation problems, which can contribute to autoimmune conditions.

What It Is

This genetic test looks for mutations in the MTHFR gene, which affect how the body processes folate and homocysteine.

Why It’s Ordered

Elevated homocysteine levels have been linked to increased inflammation and autoimmune flare-ups. Testing for MTHFR mutations helps practitioners design personalized treatment plans, including nutritional supplementation.

What It Reveals 

MTHFR mutations can lead to impaired methylation, contributing to systemic inflammation, detoxification problems, and potentially autoimmune diseases.

8. Comprehensive Stool Testing

Gut health plays a central role in autoimmune conditions, and functional medicine often starts by assessing the gut with comprehensive digestive and microbiome tests.

What It Is

Comprehensive stool testing evaluates the gut microbiome, inflammation markers, and digestive function. Tests like the GI Effects or GI-MAP test are commonly used stool analyses that screen for pathogens, bacteria, parasites, and markers of gut permeability.

Why It’s Ordered

Many autoimmune conditions are linked to gut dysfunction and inflammation, often called "leaky gut." 

Comprehensive stool testing helps identify imbalances that may be triggering an immune response.

What It Reveals

These tests uncover bacterial imbalances, infections, or gut inflammation that may contribute to autoimmune disease, allowing for targeted interventions such as probiotics, antimicrobial herbs, or dietary changes.

9. Food Sensitivity Testing

Autoimmune patients often experience flare-ups when consuming certain foods. Food sensitivity testing helps identify these triggers.

What It Is

Food sensitivity testing measures the amount of immune chemicals produced in response to specific foods. Antibodies, including IgG and IgA, and sometimes IgM or IgE, as well as other proteins or immune cell reactivity, may be tested. 

Why It’s Ordered

Chronic inflammation from food sensitivities can exacerbate autoimmune symptoms. Identifying inflammatory triggers is foundational in creating an anti-inflammatory diet.

What It Reveals

By identifying immune reactions to foods, this test can help patients avoid triggers that worsen their condition. This can help reduce inflammation and autoimmune flares.

10. Adrenal Stress Testing

Stress exacerbates autoimmune conditions; identifying adrenal dysfunction due to chronic stress is foundational in autoimmune disease management. 

What It Is

Adrenal stress testing, often done via saliva or blood, measures cortisol levels throughout the day.

Why It’s Ordered

Chronic stress can worsen autoimmune conditions by increasing inflammation and dysregulating immune function. Practitioners order this test to understand how stress impacts the patient’s overall health.

What It Reveals

Abnormal cortisol patterns can suggest adrenal fatigue or hyperactivity, providing guidance for stress management interventions such as adaptogenic herbs or lifestyle modifications.

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Key Takeaways

• Comprehensive Autoimmune Testing and Disease Specific Testing: Functional medicine practitioners use comprehensive autoimmune panels and disease-specific panels, including tests like ANA, CRP, and ESR, to assess inflammation and identify autoimmune activity for insight into underlying autoimmune processes and diagnostic insight.

• Personalized Lab Insights: functional medicine also employs additional tests including genetic, stool, and adrenal stress testing to uncover underlying causes of autoimmune conditions, tailoring treatments based on inflammation, gut health, and stress levels.