Autoimmunity: organ-specific (e.g., Graves disease)

5 ASCP MLS practice questions on Autoimmunity: organ-specific (e.g., Graves disease), part of Immunology. The first 5 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Medium

   A 50-year-old has painful mouth erosions and fragile skin blisters that break easily. Direct immunofluorescence of a skin biopsy shows IgG between the epidermal cells in a net-like pattern. Which antigen is the target?

   1. ADesmoglein 3
   2. BBP180 (collagen XVII)
   3. CType VII collagen
   4. DEpidermal transglutaminase

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   Answer: A · Desmoglein 3

   Pemphigus vulgaris is caused by IgG antibodies to desmoglein 3, a desmosome protein that holds keratinocytes together; mucosal disease is typical, and desmoglein 1 antibodies are added when the skin is widely involved. Loss of cell adhesion (acantholysis) gives flaccid blisters that break easily, and direct immunofluorescence shows IgG between epidermal cells in a net-like pattern. Bullous pemphigoid instead targets BP180 and BP230 at the basement membrane, giving tense blisters and linear staining. Serum antibodies to desmogleins 1 and 3 can be measured by ELISA to support the diagnosis and follow treatment.

   • B: BP180 is the bullous pemphigoid antigen, with linear basement membrane staining and tense blisters.
   • C: Type VII collagen is the target in epidermolysis bullosa acquisita, below the basement membrane.
   • D: Epidermal transglutaminase is the target in dermatitis herpetiformis, with granular IgA in the dermal papillae.

2. Question 2 · Hard

   A 34-year-old woman has jaundice and fatigue. Results: ALT 820 U/L (reference 7-40); ALP mildly raised; polyclonal IgG markedly raised; ANA positive; anti-smooth muscle (anti-actin) positive; antimitochondrial and anti-LKM-1 negative; viral hepatitis markers negative. What is the most likely diagnosis?

   1. AAutoimmune hepatitis type 2
   2. BPrimary sclerosing cholangitis
   3. CAutoimmune hepatitis type 1
   4. DPrimary biliary cholangitis

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   Answer: C · Autoimmune hepatitis type 1

   A hepatitic pattern with very high aminotransferases, a raised polyclonal IgG, ANA and anti-smooth muscle (anti-actin) antibodies, and no viral cause, is typical of type 1 autoimmune hepatitis, the commonest form in adults. Type 2 is marked by anti-LKM-1 (or anti-LC1) and mostly affects children. Primary biliary cholangitis is cholestatic, with a high ALP and antimitochondrial antibodies. Liver biopsy showing interface hepatitis supports the diagnosis, and the disease usually responds to corticosteroids.

   • A: Type 2 autoimmune hepatitis is marked by anti-LKM-1, which is negative here.
   • B: Primary sclerosing cholangitis is cholestatic and is linked to atypical P-ANCA and ulcerative colitis.
   • D: Primary biliary cholangitis is cholestatic with antimitochondrial antibodies, which are negative here.

3. Question 3 · Easy

   Myasthenia gravis is most often caused by autoantibodies against:

   1. AAquaporin-4 water channels
   2. BVoltage-gated calcium channels
   3. CAcetylcholine receptors
   4. DMyelin basic protein

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   Answer: C · Acetylcholine receptors

   In most patients with generalized myasthenia gravis, IgG antibodies bind acetylcholine receptors at the neuromuscular junction, block them and cause their loss through complement-mediated damage. The result is muscle weakness that worsens with use, often starting with drooping eyelids and double vision. A smaller group has antibodies to muscle-specific kinase (MuSK) instead. Thymus abnormalities, such as thymoma or thymic hyperplasia, are common in this disease.

   • A: Aquaporin-4 antibodies cause neuromyelitis optica.
   • B: Voltage-gated calcium channel antibodies cause Lambert-Eaton myasthenic syndrome.
   • D: Myelin basic protein is a target studied in multiple sclerosis, not myasthenia.

4. Question 4 · Easy

   The antibodies that cause hyperthyroidism in Graves disease bind:

   1. AThyroglobulin
   2. BThe TSH receptor
   3. CThe sodium-iodide symporter
   4. DThyroid peroxidase

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   Answer: B · The TSH receptor

   In Graves disease, thyroid-stimulating immunoglobulins bind the TSH receptor and act like TSH, so the gland makes too much hormone while pituitary TSH is suppressed. These IgG antibodies can cross the placenta and cause neonatal hyperthyroidism. Antibodies to thyroid peroxidase and thyroglobulin are often present too, but they do not stimulate the gland. TSH receptor antibody testing helps diagnose Graves disease and assess fetal risk in pregnancy.

   • A: Thyroglobulin antibodies mark thyroid autoimmunity but do not cause hyperthyroidism.
   • C: The sodium-iodide symporter is not the target of the stimulating antibodies.
   • D: Thyroid peroxidase antibodies mark autoimmune thyroiditis and do not stimulate the gland.

5. Question 5 · Medium

   A 9-year-old has new hyperglycemia, weight loss and ketonuria. Which antibody panel best supports autoimmune type 1 diabetes?

   1. AGAD65, IA-2 and zinc transporter 8
   2. BAcetylcholine receptor and MuSK
   3. CThyroid peroxidase and thyroglobulin
   4. DTissue transglutaminase and endomysium

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   Answer: A · GAD65, IA-2 and zinc transporter 8

   Type 1 diabetes results from T cell destruction of pancreatic beta cells, and antibodies to GAD65, IA-2 (insulinoma-associated antigen 2), zinc transporter 8 and insulin are its markers. Most children are positive for at least one at diagnosis, and two or more predict disease in relatives. Insulin autoantibodies are useful only before, or very soon after, insulin treatment starts. Children with type 1 diabetes are also screened for celiac and thyroid autoimmunity, which often occur with it.

   • B: Acetylcholine receptor and MuSK antibodies mark myasthenia gravis.
   • C: Thyroid peroxidase and thyroglobulin antibodies mark autoimmune thyroid disease.
   • D: Tissue transglutaminase and endomysial antibodies mark celiac disease.