Welcome to USMLE practice question #146! Today’s topic is immunology.
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A 35-year-old woman presents to the clinic with a 3-week history of fever, fatigue, joint pain, and a malar rash. Laboratory tests reveal proteinuria and the presence of anti-dsDNA antibodies. A renal biopsy shows immune complex deposition in the glomeruli. Which of the following best explains the pathophysiology of this patient’s condition?
A) Type I hypersensitivity
B) Type II hypersensitivity
C) Type III hypersensitivity
D) Type IV hypersensitivity
E) Mixed hypersensitivity reaction
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
It’s important to adopt the correct MENTAL MODEL when answering USMLE questions; it saves time and increases accuracy. The mental model outlined below is a foundational component of our test-taking skills masterclass (check it out if you want to elevate your skills). Here’s how to think through this question:
Step 1. Read the last line to get to the heart of the question: “Which of the following best explains the pathophysiology of this patient’s condition?”
Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order. 1st: Make a diagnosis, 2nd: Identify the associated type of hypersensitivity reaction.
Step 3: Read the vignette carefully and ask yourself: “Based on the diagnosis, this is a _________________________.”
Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.
GENERAL ANALYSIS
The patient presents with systemic lupus erythematosus (SLE), as evidenced by fever, fatigue, joint pain, malar rash, proteinuria, and anti-dsDNA antibodies. The renal biopsy showing immune complex deposition in the glomeruli confirms lupus nephritis, a severe manifestation of SLE.
ANSWER CHOICES:
CHOICE A: Type I hypersensitivity
Explanation: Type I hypersensitivity is mediated by IgE antibodies and involves mast cell degranulation, leading to allergic reactions such as anaphylaxis or asthma.
CHOICE B: Type II hypersensitivity
Explanation: Type II hypersensitivity involves IgG or IgM antibodies directed against cell surface antigens, leading to complement activation and cytotoxicity (e.g., autoimmune hemolytic anemia).
CHOICE C: Type III hypersensitivity
Explanation: Type III hypersensitivity involves the formation of antigen-antibody complexes that deposit in tissues, triggering complement activation and recruitment of inflammatory cells.
CHOICE D: Type IV hypersensitivity
Explanation: Type IV hypersensitivity is mediated by T cells and macrophages and is responsible for delayed-type reactions such as contact dermatitis or granulomatous inflammation.
CHOICE E: Mixed hypersensitivity reaction
Explanation: Mixed hypersensitivity would involve multiple types of immune responses simultaneously. While SLE can have features of type II and type III hypersensitivities, the dominant mechanism in lupus nephritis is type III hypersensitivity.
FINAL VERDICT…
CORRECT ANSWER: C) Type III hypersensitivity
The underlying pathophysiology of her condition is a type III hypersensitivity reaction, which involves the formation and deposition of immune complexes (antigen-antibody complexes) in tissues, leading to inflammation and tissue damage.
KEY CONCEPTS:
Pathophysiology of SLE (Type III Hypersensitivity):
Autoantibodies (e.g., anti-dsDNA) form immune complexes with nuclear antigens.
These immune complexes deposit in tissues such as the kidneys, skin, and joints.
Complement activation leads to inflammation and tissue damage.
Lupus Nephritis (Renal Manifestation of SLE):
Immune complexes deposit in the glomeruli.
Complement activation attracts inflammatory cells, causing glomerular injury.
Clinical features include proteinuria, hematuria, hypertension, and renal dysfunction.
Hypersensitivity Reaction Types in SLE:
Type II: Autoimmune hemolytic anemia or thrombocytopenia due to antibodies against blood cells.
Type III: Immune complex-mediated tissue damage (e.g., lupus nephritis).
Type IV: Rarely involved but may contribute to some inflammatory responses.
Diagnosis of Lupus Nephritis:
Positive anti-dsDNA antibodies.
Low complement levels (C3, C4).
Renal biopsy showing immune complex deposition.
Management of Lupus Nephritis:
Immunosuppressive therapy (e.g., corticosteroids, mycophenolate mofetil).
Control of systemic lupus activity.