I am going to answer the sample USMLE Step 1 Questions with Explanation. These questions are available at USMLE.org
A 32-year-old man comes to the office because of a 1-day history of cough productive of small amounts of blood and a 2-day history of shortness of breath and swelling of his ankles. He also has a 2-week history of progressive fatigue and episodes of dark urine. He has no history of major medical illness and takes no medications. His temperature is 37°C(98.6°F), pulse is 90/min, respirations are 18/min, and blood pressure is 175/110 mm Hg. Pulse oximetry on room airshows an oxygen saturation of 91%. Diffuse inspiratory crackles are heard over all lung bases. There is 2+ pitting edema of both ankles. Results of laboratory studies are shown:
Hemoglobin 8.9 g/dL
Hematocrit 27%
Serum Urea nitrogen 55 mg/dL
Creatinine 2.9 mg/dL
Urine RBC 20–40/hpf
Urinalysis also shows some dysmorphic RBCs and rare RBC casts. Examination of a kidney biopsy specimen shows crescentic glomerulonephritis and linear deposition of IgG along the glomerular capillaries. This patient most likely has antibodies directed against which of the following antigens?
(A) Collagen
(B) Double-stranded DNA
(C) Nucleolar protein
(D) Phospholipid
(E) Proteins in neutrophil cytoplasm
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Answer
The patient’s presentation is indicative of Goodpasture syndrome, characterized by pulmonary hemorrhage and rapidly progressive glomerulonephritis (RPGN). In Goodpasture syndrome, there is an autoimmune attack on the basement membrane of the lungs and kidneys, resulting in the production of autoantibodies against the alpha-3 chain of type IV collagen, which is a major component of the basement membrane in these organs.
(A) Collagen: This option does not specify the type of collagen. While antibodies against collagen can occur in various autoimmune diseases, the specific target in Goodpasture syndrome is the alpha-3 chain of type IV collagen.
(B) Double-stranded DNA: Antibodies against double-stranded DNA are characteristic of systemic lupus erythematosus (SLE) but are not associated with Goodpasture syndrome.
(C) Nucleolar protein: Antibodies against nucleolar proteins are often seen in systemic sclerosis (scleroderma) but are not relevant to the presentation of Goodpasture syndrome.
(D) Phospholipid: Antibodies against phospholipids are associated with antiphospholipid syndrome but are not related to Goodpasture syndrome.
(E) Proteins in neutrophil cytoplasm: This option refers to anti-neutrophil cytoplasmic antibodies (ANCA), associated with certain forms of vasculitis, but not Goodpasture syndrome.
Given the patient’s clinical presentation and the characteristic linear deposition of IgG along the glomerular capillaries observed on kidney biopsy, the most likely antigen targeted in this case is the basement membrane protein, specifically the alpha-3 chain of type IV collagen.
Therefore, the correct answer is: (A) Collagen
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