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Thyroid, rheumatoid and organ-specific autoantibodies

15 min

  • Choose the antibody tests that fit a suspected organ-specific disease
  • Tell thyroid antibody results from thyroid function, and TRAb binding from stimulation
  • Tell a nonspecific rheumatoid factor result from a more specific anti-CCP result

Read the full reference

Try first

Try first

A celiac screen reports IgA anti-tissue transglutaminase (anti-tTG) as negative. No total IgA was measured. What does the laboratory need before that negative result can be relied on?

The next section explains it.

Right. The next section explains why.

The next section explains it.

The next section explains it.

The next section explains it.

Get the idea

Pair the antibody with the organ

An organ-specific autoantibody is most useful beside evidence from the organ itself: hormone levels, enzymes, function tests or tissue findings.1 Each suspected disease has its own first antibody.

Suspected diseaseFirst antibody tests
Hashimoto thyroiditisAnti-thyroid peroxidase (anti-TPO)
Graves diseaseTSH receptor antibody (TRAb)
Celiac diseaseIgA anti-tTG with total IgA
Autoimmune hepatitis type 1ANA and smooth muscle antibody
Primary biliary cholangitisAntimitochondrial antibody
Rheumatoid arthritisRheumatoid factor and anti-CCP

1-5

Celiac serology needs IgA

IgA anti-tTG is the first celiac test in a patient eating gluten. A patient with IgA deficiency cannot make IgA anti-tTG, so every IgA screen is paired with a total IgA. When total IgA is very low, an IgG-based test such as IgG anti-deamidated gliadin peptide follows. A gluten-free diet lowers the antibody and can make any celiac test falsely negative.4

Thyroid antibodies name a cause

Thyroid function comes from TSH and free T4. Anti-TPO supports Hashimoto thyroiditis, and TRAb supports Graves disease. A positive antibody names a likely cause and says nothing about whether the gland is overactive, underactive or working normally today.2

TRAb comes in two formats. A binding assay detects any antibody that attaches to the TSH receptor, whether it stimulates or blocks the receptor. A bioassay measures what the antibody does to receptor-bearing cells, and only a bioassay reports stimulating activity. The report names which format was used.2

Rheumatoid factor and anti-CCP

Rheumatoid factor is usually IgM against the Fc region of IgG. It appears in other inflammatory diseases, in infections and in some healthy people, especially older adults. Anti-cyclic citrullinated peptide (anti-CCP) antibody is more specific for rheumatoid arthritis and can be positive when RF is negative. Neither antibody alone establishes the disease or its current activity. Both are read with the joint findings.1,3

References
  1. Abbas AK, Lichtman AH, Pillai S, Henrickson S. Cellular and Molecular Immunology. 11th ed. Elsevier; 2025. Elsevier.
  2. ARUP Laboratories. Autoimmune thyroiditis. ARUP Consult. Accessed September 27, 2026.
  3. ARUP Laboratories. Rheumatoid arthritis. ARUP Consult. Accessed September 27, 2026.
  4. Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023;118(1):59-76. doi:10.14309/ajg.0000000000002075
  5. ARUP Laboratories. Primary biliary cholangitis. ARUP Consult. Accessed September 27, 2026.

Watch one

Oskar Lindqvist, 27, is a line cook who tastes everything he makes, bread included. His provider orders a celiac screen for chronic diarrhea and iron deficiency.

Can the negative IgA anti-tTG be reported as a negative celiac screen?

TestResultPreviousReference intervalFlag
IgA anti-tTG0.8 U/mL<4.0 U/mL
Total IgA<5 mg/dL70–400 mg/dLLow
IgG1,080 mg/dL700–1,600 mg/dL
IgM115 mg/dL40–230 mg/dL

Specimen: H 3, L 12, I 1. Serum, collected 08:40

  1. Check the history first. He eats gluten every day, so the screen was done at a useful time.

    Celiac antibodies fall when gluten leaves the diet, so every screen is read against intake.

  2. Read the total IgA next. It is below 5 mg/dL, far under the reference interval.

    The IgA screen depends on the patient's ability to make IgA.

  3. Check the other immunoglobulins. IgG and IgM are both within their reference intervals.

    IgG and IgM within their intervals point to a selective loss of IgA.

  4. Now read the anti-tTG. The 0.8 U/mL result is uninformative in this patient.

    A patient who makes almost no IgA cannot make IgA anti-tTG.

  5. Choose the follow-up. An IgG-based test, such as IgG anti-deamidated gliadin peptide, follows under the laboratory's algorithm.

    An IgG-based antibody does not depend on IgA production.

No. Report the IgA anti-tTG with a comment that total IgA is below 5 mg/dL, too low to interpret an IgA-based result. IgG-based celiac testing follows.

Your turn

Problem 1 of 3

Anti-TPO is 180 IU/mL (reference <35 IU/mL). TSH is 2.3 mIU/L and free T4 is 1.1 ng/dL, both within their reference intervals. What does this result set show?

Hypothyroidism shows as a high TSH with a low free T4. Both are within their intervals here.

Anti-TPO is often positive before thyroid function changes. A normal TSH does not make the antibody result wrong.

Anti-TPO supports autoimmune thyroid disease. TSH and free T4 describe current function, and both are within their intervals.

Graves disease is supported by TSH receptor antibody with a low TSH and high free T4. Neither is present here.

Hint
  1. Decide which tests measure what the gland is doing today.
  2. Ask what an antibody result can add once function has been measured.

Review Thyroid autoantibodies

Problem 2 of 3

A 74-year-old woman with no joint symptoms has rheumatoid factor 40 IU/mL (reference <14 IU/mL) on a broad screening panel. Anti-CCP was not ordered. How does the laboratory read the RF?

RF appears in other inflammatory diseases, infections and healthy older adults. A positive result alone does not establish rheumatoid arthritis.

Read RF positivity alone as rheumatoid arthritis

Rheumatoid factor, usually IgM against the Fc region of IgG, also occurs in other diseases and in healthy people, and anti-CCP is generally more specific. A positive RF alone does not mean rheumatoid arthritis.

A positive RF in an older adult is common and expected. Nothing in the result points to a specimen problem.

RF does not measure disease activity. She has no joint symptoms at all.

RF has limited specificity. Anti-CCP is the more specific antibody, and both are read with the joint findings.

Hint
  1. Recall who else carries rheumatoid factor.
  2. Age matters for this antibody.

Review Rheumatoid factor and anti-CCP

Problem 3 of 3

A 58-year-old woman has itching and a cholestatic liver pattern with a high alkaline phosphatase. Her provider asks for the antibody test that best supports primary biliary cholangitis. Which one fits?

Smooth muscle antibody supports type 1 autoimmune hepatitis. It is not the marker for primary biliary cholangitis.

Anti-LKM1 supports type 2 autoimmune hepatitis, which is seen mostly in children.

Antimitochondrial antibody is present in more than 90% of patients with primary biliary cholangitis. It is read with the liver chemistry pattern.

IgA anti-tTG is the celiac screen. Celiac disease can raise liver enzymes, but the test does not address biliary autoimmunity.

Review Organ-specific autoimmune patterns

Use it

  • Delphine Okafor, 46, is a pastry chef who has stopped kneading dough by hand because her fingers ache and swell every morning.
  • She has also lost weight and feels her heart racing.
  • Her provider orders joint and thyroid serology.
  • The laboratory's TRAb method is a receptor-binding immunoassay.
TestResultPreviousReference intervalFlag
Rheumatoid factor9 IU/mL<14 IU/mL
Anti-CCP86 U/mL<20 U/mLHigh
TSH0.02 mIU/L0.40–4.50 mIU/LLow
Free T43.1 ng/dL0.8–1.8 ng/dLHigh
TSH receptor antibody6.4 IU/L≤1.75 IU/LHigh

Specimen: H 2, L 9, I 1. Serum, collected 09:15

Decision 1 of 2

How does the laboratory read the RF and anti-CCP pair?

Rheumatoid arthritis can be RF-negative. Anti-CCP can be positive when RF is not.

RF-negative, anti-CCP-positive results are a recognized pattern. Nothing points to a specimen problem.

Anti-CCP is more specific for rheumatoid arthritis than RF. Both results are released and read with her joint findings.

Review Rheumatoid factor and anti-CCP

Decision 2 of 2

How is the TSH receptor antibody reported?

A binding assay detects stimulating and blocking antibodies together. The report names the format so no one reads activity into it.

The high free T4 is a separate result. The binding assay did not measure what the antibody does to the receptor.

Inferred stimulating activity from every TRAb binding test

TSH receptor antibody (TRAb) binding assays detect antibody to the receptor whether it stimulates or blocks the receptor. Functional bioassays measure the antibody's effect on receptor-bearing cells. Reporting stimulating antibody from a binding assay claims a property the method did not measure.

Blocking activity also needs a functional test. A low TSH does not tell the assay which kind of antibody bound.

Review Thyroid autoantibodies

The clue that settled this case is the method behind each antibody. Anti-CCP is the specific rheumatoid marker, so a negative RF does not undo it. The TRAb came from a binding assay, so the report states binding and leaves stimulating activity unmeasured. TSH and free T4 describe what her thyroid is doing.

Keep

Sources checked