Autoimmune Diseases HARR

Question 1

What is a general definition for autoimmunity?
A. Increase of tolerance to self-antigens
B. Loss of tolerance to self-antigens
C. Increase in clonal deletion of mutant cells
D. Manifestation of immunosuppression

Answer 1

Loss of tolerance to self-antigens

Autoimmunity is a loss of tolerance to self-antigens and the subsequent formation of autoantibodies.

Question 2

An antinuclear antibody test is performed on a
specimen from a 55-year-old woman who has
unexplained joint pain. The IFA result is a titer of 40 and a homogeneous pattern. The appropriate follow-up for this patient is:
A. Anti-DNA assay
B. Extractable nuclear antigen (ENA) testing
C. Retest ANA in 3–6 months
D. CH50 complement assay

Answer 2

Retest ANA in 3–6 months

Approximately 25% of women in this age range
may have low titer-positive ANA assays with no
demonstrable connective tissue disease. A patient with anti-DNA–positive SLE would be expected to have a much higher titer (> 160) in an IFA assay. A similar titer would be expected for an ENA positive specimen, although the pattern would be speckled. Complement testing would not be indicated with this low titer in a 55-year-old female.

Question 3

Which disease is likely to show a rim (peripheral) pattern in an immunofluorescence (IF) microscopy test for ANA?
A. Mixed connective tissue disease (MCTD)
B. Rheumatoid arthritis
C. Systemic lupus erythematosus
D. Scleroderma

Answer 3

Systemic lupus erythematosus

The rim or peripheral pattern seen in indirect
immunofluorescence techniques is most
commonly found in cases of active SLE. The
responsible autoantibody is highly correlated to anti–double-stranded DNA (anti-dsDNA)

Question 4

A patient’s specimen is strongly positive in an
ANA ELISA. Which of the following would not be an appropriate follow up to this result?
A. Immunofluorescence test on HEp-2 cells
B. Specific ENA ELISA tests
C. Specific anti-DNA ELISA
D. Rheumatoid factor assay

Answer 4

Rheumatoid factor assay

The ANA ELISA is a screening assay. A positive result may be followed up by more specific antibody ELISA tests or an ANA immunofluorescence test to determine pattern and titer. The ANA ELISA does not screen for rheumatoid factor.

Question 5

What type of antibodies is represented by the solid or homogeneous pattern in the immunofluorescence test for antinuclear antibodies?
A. Antihistone antibodies
B. Anticentromere antibodies
C. Anti-ENA (anti-Sm and anti-RNP) antibodies
D. Anti-RNA antibodies

Answer 5

Antihistone antibodies

Antihistone antibodies (and also anti-DNA antibodies) cause the solid or homogeneous pattern, which is commonly found in patients with SLE, RA, mixed connective tissue disease, and Sjögren’s syndrome. Antibodies to the centromere of chromosomes is a marker for the CREST (calcinosis, Raynaud’s phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia) form of systemic sclerosis.

Question 6

What disease is indicated by a high titer of
anti-Sm (anti-Smith) antibody?
A. Mixed connective tissue disease (MCTD)
B. RA
C. SLE
D. Scleroderma

Answer 6

SLE

High titer anti-Sm is indicative of SLE. Anti-Sm is one of two antibodies against saline extractable nuclear antigens, the other being anti-RNP. These antibodies cause a speckled pattern of immunofluorescence.

Question 7

Which disease is least likely when a nucleolar
pattern occurs in an immunofluorescence test for antinuclear antibodies?
A. MCTD
B. Sjögren’s syndrome
C. SLE
D. Scleroderma

Answer 7

MCTD

All of the diseases except MCTD may cause a
nucleolar pattern of immunofluorescence. Nucleolar fluorescence is caused by anti-RNA antibodies and is seen in about 50% of patients with scleroderma

Question 8

What antibodies are represented by the nucleolar pattern in the immunofluorescence test for antinuclear antibodies?
A. Antihistone antibodies
B. Anti-dsDNA antibodies
C. Anti-ENA (anti-Sm and anti-RNP) antibodies
D. Anti-RNA antibodies

Answer 8

Anti-RNA antibodies

Anti-RNA antibodies are represented by the nucleolar pattern. This pattern may be seen in most systemic autoimmune diseases and is especially common in patients with scleroderma. Anti-RNA and anti-Sm are not usually found in patients with mixed connective tissue disease. This is a syndrome involving aspects of SLE, RA, scleroderma, and polymyositis. The immunofluorescence pattern most often seen in MCTD is the speckled pattern caused by anti-RNP

Question 9

Which test would best distinguish between SLE
and MCTD?
A. Multiplex or ELISA test for anti-SM and
anti-RNP
B. Immunofluorescence testing using Crithidia as substrate
C. Slide agglutination testing
D. Laboratory tests cannot distinguish between
these disorders

Answer 9

Multiplex or ELISA test for anti-SM and
anti-RNP

The Ouchterlony (double) immunodiffusion assay may be used to identify and differentiate anti-Sm from anti-RNP. Multiplex and ELISA assays, using purified or recombinant antigens, are also available for this testing. Anti-Sm with or without anti-RNP is found in approximately one third of SLE patients. Anti-RNP in the absence of anti-Sm is found in over 95% of MCTD patients.

Question 10

An ANA test on HEp-2 cells shows nucleolar
staining in interphase cells and dense chromatin staining in mitotic cells. The most likely cause of this staining pattern is:
A. Antifibrillarin antibody
B. Antiribosomal p antibody
C. A serum with nucleolar and homogeneous
patterns
D. Technical artifact

Answer 10

Antifibrillarin antibody

Antifibrillarin antibody has this appearance.
Ribosomal p antibody has nucleolar staining and a background homogeneous and cytoplasmic stain. A combination nucleolar/homogeneous specimen will also show homogeneous staining in the interphase cells. This pattern is not seen in typical
technical artifacts.

Question 11

Which immunofluorescence pattern indicates
the need for ENA testing by Ouchterlony
immunodiffusion, Multiplex, or ELISA assays?
A. Homogeneous or solid
B. Peripheral or rim
C. Speckled
D. Nucleolar

Answer 11

Speckled

A speckled pattern is often due to the presence of antibodies against the extractable nuclear antigens, such as Sm, RNP, SSA, and SSB. Homogenous and rim patterns suggest antibodies to double-stranded DNA. The homogeneous pattern may also be seen with
antibodies to deoxyribonuclear protein, which is not an ENA. Nucleolar patterns often indicate antibodies to RNA or fibrillarin

Question 12

Which of the following is used in rapid slide tests for detection of rheumatoid factors?
A. Whole IgM molecules
B. Fc portion of the IgG molecule
C. Fab portion of the IgG molecule
D. Fc portion of the IgM molecule

Answer 12

Fc portion of the IgG molecule

Rheumatoid factors react with the Fc portion of the IgG molecule and are usually IgM. This is the basis of rapid agglutination tests for RA. Particles of latex or cells are coated with IgG. Addition of serum containing rheumatoid factor results in visible agglutination.

Question 13

Which of the following methods is least likely to give a definitive result for the diagnosis of RA?
A. Nephelometric measurement of anti-IgG
B. Agglutination testing for rheumatoid factor
C. Anti CCP
D. Immunofluorescence testing for antinuclear
antibodies

Answer 13

Immunofluorescence testing for antinuclear
antibodies

Patients with RA often show a homogeneous pattern of fluorescence in tests for antinuclear antibodies. However, this pattern is seen in a wide range of systemic autoimmune diseases and in many normal persons at a titer below 10. The first two methods listed may be used to identify anti-IgG, which is required to establish a diagnosis of RA Anti CCP is a specific assay for rheumatoid arthritis.

Question 14

Which disease might be indicated by antibodies to smooth muscle?
A. Atrophic gastritis
B. Autoimmune hepatitis
C. Myasthenia gravis
D. Sjögren’s syndrome

Answer 14

Autoimmune hepatitis

Antibodies to smooth muscle are found in the serum of up to 70% of patients with active chronic hepatitis and up to 50% of patients with primary biliary cirrhosis.

Question 15

Antibodies to thyroid peroxidase can be detected by using agglutination assays. Which of the following diseases may show positive results with this type of assay?
A. Graves’ disease and Hashimoto’s thyroiditis
B. Myasthenia gravis
C. Granulomatous thyroid disease
D. Addison’s disease

Answer 15

Graves’ disease and Hashimoto’s thyroiditis

Antibodies to thyroid peroxidase may be detected in both Graves’ disease (hyperthyroidism) and Hashimoto’s thyroiditis (hypothyroidism). If a positive result is found to thyroid peroxidase, thyroxine levels can be measured to distinguish between the two
diseases.

Question 16

What is the main use of laboratory tests to detect antibodies to islet cells and insulin in cases of insulin-dependent diabetes mellitus (IDDM)?
A. To regulate levels of injected insulin
B. To diagnose IDDM
C. To rule out the presence of other autoimmune diseases
D. To screen susceptible individuals prior to
destruction of β cells

Answer 16

To screen susceptible individuals prior to
destruction of β cells

Fasting hyperglycemia is the primary finding used to diagnose IDDM. For individuals with an inherited susceptibility to the development of IDDM, laboratory tests for the detection of antibodies to islet cells and insulin may help to initiate early treatment before complete destruction of β cells.

Question 17

A patient presents with clinical symptoms of celiac disease. Tests for anti-tissue transglutaminase and antigliadin antibodies are negative. Which of the following tests should be ordered?
A. IgG level
B. HLA DQ typing
C. HLA DR typing
D. IgM level

Answer 17

HLA DQ typing

While antibodies to tissue transglutaminase and gliadin are often found in celiac disease, their combined sensitivity is less than 100%. Celiac disease is almost exclusively associated with the presence of HLA DQ2 and/or HLA DQ8. These HLA genes are not diagnostic of celiac disease, but provide a testing alternative in antibody-negative individuals who meet the clinical diagnostic criteria for celiac disease

Question 18

A specimen appears to have a perinuclear staining pattern in an antineutrophil cytoplasmic antibody (ANCA) immunofluorescent assay using ethanolfixed neutrophils, suggesting the possibility of a
pANCA. On which of the following substrates
would this specimen display cytoplasmic
speckling?
A. Formalin-fixed neutrophils
B. Unfixed neutrophils
C. HEp-2 cells
D. Rabbit kidney tissue

Answer 18

Formalin-fixed neutrophils

Antibodies to neutrophil cytoplasmic antigen
demonstrating a perinuclear pattern of fluorescence indicate a diagnosis of vasculitis. However, atypical ANCAs and ANAs also demonstrate a perinuclear staining pattern on ethanol-fixed neutrophils. To differentiate these from pANCA, specimens appearing as a pANCA on ethanol-fixed cells are tested on formalin-fixed neutrophils. The myeloperoxidase containing granules that coalesce around the nuclear membrane during ethanol fixation will remain in the cytoplasm during formalin fixation. Thus, pANCA will have a cytoplasmic (cANCA) pattern on a formalin-fixed slide, but ANAs will retain a perinuclear pattern and the fluorescence will be diminished.