Skip to content

Add your earlier progress to your account?

From before you signed in, this browser has:

Which plan do you want to keep?

You answered the plan questions before you signed in, and those answers don't match the plan saved on your account.

SettingSaved planNew answers

Study progress is waiting to be saved

Thyroid, rheumatoid and organ-specific autoantibodies

15 min

Skills you'll build3 skills
  • 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

At the bench: Interpret an autoantibody pattern with its confirmation results

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?

Keep going to see the reasoning.

Right. Keep going to follow the reasoning.

Keep going to see the reasoning.

Keep going to see the reasoning.

Keep going to see the reasoning.

Get the idea

Use the explanation to check your first decision.

Organ-specific antibodies

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

Thyroid function is assessed with TSH and free T4. Anti-TPO supports Hashimoto thyroiditis, and TRAb supports Graves disease. A positive antibody suggests a likely cause. It does not show whether the gland is currently overactive, underactive or functioning normally.2

TRAb assays come 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. A positive result for either antibody does not establish the disease or its current activity. Both are interpreted with the joint findings.1,3

Follow the bench demonstration

Sources for this step
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

Read each decision and its explanation.

Oskar Washburn, 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?

TestResultReference intervalFlag
IgA anti-tTG0.8 U/mL<4.0 U/mL<4.0
Total IgA<5 mg/dL Low70–400 mg/dL70–400Low
IgG1,080 mg/dL700–1,600 mg/dL700–1,600
IgM115 mg/dL40–230 mg/dL40–230

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

  1. Check the history first. He eats gluten every day, so the timing of the screen is appropriate.

    Celiac antibodies fall when gluten leaves the diet, so every screen is interpreted with the patient's gluten intake.

  2. Read the total IgA next. It is below 5 mg/dL, far below 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 suggest selective IgA deficiency.

  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.

Practice this skill

Your turn

Problem 1 of 3 · Hints available

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 current thyroid function.
  2. Ask what an antibody result can add once function has been measured.

Review Thyroid autoantibodies

Problem 2 of 3 · Hints available

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 interpret 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 suggests a specimen problem.

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

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

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

Review Rheumatoid factor and anti-CCP

Problem 3 of 3 · On your own

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 interpreted 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

Read the case evidence, then make each decision. The step is complete without it.

  • Delphine Piper, 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.
TestResultReference intervalFlag
Rheumatoid factor9 IU/mL<14 IU/mL<14
Anti-CCP86 U/mL High<20 U/mL<20High
TSH0.02 mIU/L Low0.40–4.50 mIU/L0.40–4.50Low
Free T43.1 ng/dL High0.8–1.8 ng/dL0.8–1.8High
TSH receptor antibody6.4 IU/L High≤1.75 IU/L≤1.75High

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

Decision 1 of 2

How does the laboratory interpret the RF and anti-CCP results?

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 suggests a specimen problem.

Anti-CCP is more specific for rheumatoid arthritis than RF. Both results are released and interpreted 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 stimulating activity is not assumed.

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 show which kind of antibody bound in the assay.

Review Thyroid autoantibodies

Each antibody is interpreted by what its method measures. Anti-CCP is the more specific rheumatoid marker, so a negative RF does not cancel a positive anti-CCP. The TRAb came from a binding assay, so the report states binding and does not report stimulating activity. TSH and free T4 describe her current thyroid function.

For reference

Sources checked