A 46-year-old man has had fever, night sweats, weight loss and aching wrists and knees for 6 weeks; he had a dental extraction 2 months ago. There is no joint swelling, but he has a new mitral murmur and splinter hemorrhages. Results: rheumatoid factor 88 IU/mL (reference below 14); anti-CCP 3 U/mL (below 17); ANA negative; CRP 96 mg/L (below 5); ESR 92 mm/h; C3 0.68 g/L (0.90-1.80); urine shows microscopic hematuria; anti-HCV nonreactive. The positive rheumatoid factor is best explained by:

Subacute infective endocarditis

Hepatitis C-related cryoglobulinemia

Seropositive rheumatoid arthritis

In a patient with early inflammatory arthritis, a strongly positive anti-CCP result mainly indicates:

A higher risk of erosive, progressive disease

An active bacterial infection within the joint

That the arthritis was caused by a drug

The level of current joint inflammation

A 58-year-old woman with rheumatoid arthritis has no swollen or tender joints. Results: ESR 64 mm/h (reference below 20), CRP 3 mg/L (reference below 5), hemoglobin 98 g/L (9.8 g/dL), total protein 90 g/L (9.0 g/dL) with a broad polyclonal rise in gamma globulin. A repeat ESR on a fresh sample, with the tube vertical, is the same. What best explains the high ESR?

Anemia and raised immunoglobulins speed sedimentation

Falsely low CRP from a high-dose hook effect

Very early inflammation that CRP has not yet detected

Sample stored too long before the ESR was set up

Rheumatoid arthritis and inflammatory markers

9 DOH Abu Dhabi (HAAD) lab licensing practice questions on Rheumatoid arthritis and inflammatory markers, part of Immunology and Serology. The first 9 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 46-year-old man has had fever, night sweats, weight loss and aching wrists and knees for 6 weeks; he had a dental extraction 2 months ago. There is no joint swelling, but he has a new mitral murmur and splinter hemorrhages. Results: rheumatoid factor 88 IU/mL (reference below 14); anti-CCP 3 U/mL (below 17); ANA negative; CRP 96 mg/L (below 5); ESR 92 mm/h; C3 0.68 g/L (0.90-1.80); urine shows microscopic hematuria; anti-HCV nonreactive. The positive rheumatoid factor is best explained by:
1. ASubacute infective endocarditis
2. BHepatitis C-related cryoglobulinemia
3. CSeropositive rheumatoid arthritis
4. DSystemic lupus erythematosus
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Answer: A · Subacute infective endocarditis
Rheumatoid factor is not specific for RA: long-lasting antigen stimulation, as in subacute bacterial endocarditis, can drive IgM antibodies against the patient's own IgG. Fever, weight loss, a recent dental procedure, a new murmur and splinter hemorrhages point to endocarditis, and immune complexes explain the low C3 and the hematuria; a positive RF is one of the immunologic minor criteria in the Duke classification. Against RA, the far more specific anti-CCP is negative and there is no synovitis. Anti-HCV is nonreactive, which makes HCV-related cryoglobulinemia unlikely, and a negative ANA makes SLE very unlikely. At least three sets of blood cultures should be taken before antibiotics, and the RF usually falls after successful treatment.
- B: Anti-HCV is nonreactive, so HCV-related cryoglobulinemia is unlikely.
- C: Anti-CCP is negative and there is no synovitis, so RA is unlikely.
- D: A negative ANA makes SLE very unlikely.
Question 2 · Easy
C-reactive protein was named for its calcium-dependent binding to the C-polysaccharide of:
1. AStaphylococcus aureus
2. BStreptococcus agalactiae
3. CStreptococcus pneumoniae
4. DStreptococcus pyogenes
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Answer: C · Streptococcus pneumoniae
CRP was first found in patients with pneumococcal pneumonia, as a serum protein that precipitated the somatic C-polysaccharide of Streptococcus pneumoniae. It binds phosphocholine in that polysaccharide and on damaged cell membranes, then activates the classical complement pathway through C1q. The liver makes it under the control of IL-6, and levels can rise more than 100-fold within a day or two of acute inflammation. Laboratories now measure it by immunoturbidimetry or nephelometry.
- A: S. aureus was not the organism; its protein A binds the Fc of IgG, not CRP.
- B: Group B streptococci were not the organism; CRP was described in pneumococcal pneumonia.
- D: CRP was described with the pneumococcal polysaccharide, not the group A streptococcal cell wall.
Question 3 · Medium
In a patient with early inflammatory arthritis, a strongly positive anti-CCP result mainly indicates:
1. AAn active bacterial infection within the joint
2. BA higher risk of erosive, progressive disease
3. CThat the arthritis was caused by a drug
4. DThe level of current joint inflammation
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Answer: B · A higher risk of erosive, progressive disease
Anti-CCP is highly specific for RA, about 95%, and can appear years before symptoms. Patients who are positive, especially at high levels, are more likely to develop erosions and more severe disease, so treatment tends to be started early. Anti-CCP levels change little with treatment and are not used to follow disease activity; CRP and ESR do that. In undifferentiated arthritis, a positive result raises the chance of progression to RA.
- A: Anti-CCP is an autoantibody and does not indicate septic arthritis.
- C: Drug-induced arthritis is not marked by anti-CCP; drug-induced lupus gives antihistone antibodies.
- D: Current inflammation is followed with CRP or ESR; anti-CCP levels change little.
Question 4 · Easy
Anti-CCP antibodies recognize proteins in which arginine residues have been changed by peptidylarginine deiminase into:
1. AOrnithine
2. BHydroxyproline
3. CCitrulline
4. DHomocitrulline
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Answer: C · Citrulline
Peptidylarginine deiminase (PAD) enzymes convert arginine in proteins such as fibrin, vimentin and filaggrin into citrulline. Patients with rheumatoid arthritis make antibodies to these citrullinated proteins (ACPA), and the anti-CCP assay uses synthetic cyclic citrullinated peptides as its antigen. Smoking increases citrullination in the lungs and is a risk factor for ACPA-positive disease. The test is about as sensitive as rheumatoid factor but far more specific for RA.
- A: Ornithine is made from free arginine by arginase in the urea cycle, not by PAD in proteins.
- B: Hydroxyproline is made from proline in collagen and is not the ACPA antigen.
- D: Homocitrulline comes from lysine by carbamylation and is the target of a different antibody (anti-CarP).
Question 5 · Hard
A 58-year-old woman with rheumatoid arthritis has no swollen or tender joints. Results: ESR 64 mm/h (reference below 20), CRP 3 mg/L (reference below 5), hemoglobin 98 g/L (9.8 g/dL), total protein 90 g/L (9.0 g/dL) with a broad polyclonal rise in gamma globulin. A repeat ESR on a fresh sample, with the tube vertical, is the same. What best explains the high ESR?
1. AFalsely low CRP from a high-dose hook effect
2. BVery early inflammation that CRP has not yet detected
3. CSample stored too long before the ESR was set up
4. DAnemia and raised immunoglobulins speed sedimentation
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Answer: D · Anemia and raised immunoglobulins speed sedimentation
The ESR depends on rouleaux formation, which is increased by large asymmetric plasma proteins such as fibrinogen and immunoglobulins and by a low hematocrit. Long-standing RA often leaves anemia of chronic disease and a polyclonal rise in immunoglobulins, so the ESR can stay high after inflammation has settled. CRP is made by the liver in response to IL-6, rises within hours and falls quickly, so it reflects current activity better. When the two disagree like this, CRP is the more reliable guide.
- A: A hook effect needs extremely high CRP, which does not fit a patient with no active joints.
- B: CRP rises within hours, before the ESR, so early inflammation would raise CRP first.
- C: Delay before testing tends to lower the ESR, and the fresh repeat gave the same result.
Question 6 · Medium
Rheumatoid factor is most likely to be positive in which of these conditions?
1. ASjögren syndrome
2. BPsoriatic arthritis
3. CReactive arthritis
4. DAnkylosing spondylitis
Answer and explanation in LearnFree account
Question 7 · Hard
In the 2010 ACR/EULAR criteria, serology scores 2 points if RF or anti-CCP is low-positive (above the upper limit of normal, up to 3 times it) and 3 points if either is high-positive (more than 3 times). RF is 30 IU/mL (upper limit 14) and anti-CCP 60 U/mL (upper limit 17). The serology score is:
1. A6 points: both are high-positive
2. B3 points: anti-CCP is high-positive
3. C5 points: the two results are added
4. D2 points: both are low-positive
Answer and explanation in LearnFree account
Question 8 · Medium
Which antibody is the most specific marker for rheumatoid arthritis?
1. AAntinuclear antibody
2. BRheumatoid factor
3. CC-reactive protein
4. DAnti-CCP antibody
Answer and explanation in LearnFree account
Question 9 · Easy
What is C-reactive protein (CRP)?
1. AAn acute phase protein from the liver
2. BA tumor marker made by cancer cells
3. CAn immunoglobulin made by plasma cells
4. DA component of the complement system
Answer and explanation in LearnFree account

Rheumatoid arthritis and inflammatory markers

C-reactive protein was named for its calcium-dependent binding to the C-polysaccharide of:

In a patient with early inflammatory arthritis, a strongly positive anti-CCP result mainly indicates:

Anti-CCP antibodies recognize proteins in which arginine residues have been changed by peptidylarginine deiminase into:

Rheumatoid factor is most likely to be positive in which of these conditions?

In the 2010 ACR/EULAR criteria, serology scores 2 points if RF or anti-CCP is low-positive (above the upper limit of normal, up to 3 times it) and 3 points if either is high-positive (more than 3 times). RF is 30 IU/mL (upper limit 14) and anti-CCP 60 U/mL (upper limit 17). The serology score is:

Which antibody is the most specific marker for rheumatoid arthritis?

What is C-reactive protein (CRP)?