A 47-year-old woman comes to the physician with progressive joint pain and swelling in her hands for the past several months. She also has easy fatigability that has gradually worsened over the same period. Morning activities are especially difficult due to stiffness lasting 1 to 2 hours after waking. Examination shows warmth, swelling, and tenderness involving the proximal interphalangeal joints, metacarpophalangeal joints, and wrists bilaterally. A blood sample is obtained for laboratory analysis. Autoantibodies against which of the following components are most specific for this patient's condition?

Question

A 47-year-old woman comes to the physician with progressive joint pain and swelling in her hands for the past several months.  She also has easy fatigability that has gradually worsened over the same period.  Morning activities are especially difficult due to stiffness lasting 1 to 2 hours after waking.  Examination shows warmth, swelling, and tenderness involving the proximal interphalangeal joints, metacarpophalangeal joints, and wrists bilaterally.  A blood sample is obtained for laboratory analysis.  Autoantibodies against which of the following components are most specific for this patient's condition?

Quizplus · Accepted Answer

11ec160b_3b6a_82a2_9249_5324ccc00dc2_MD0001_00 This patient's symmetric polyarthritis (involving the MCP and PIP joints) with prolonged morning stiffness and associated fatigue is highly suggestive of rheumatoid arthritis (RA). The diagnosis is made clinically, but the presence of anti-cyclic citrullinated peptide (anti-CCP) antibodies is helpful for confirmation. Tissue inflammation causes arginine residues in proteins such as vimentin to be enzymatically converted into citrulline through a process called citrullination. This alters the shape of the proteins, which can then serve as neoantigens that generate an immune response. In RA, the immune response against citrullinated proteins is exaggerated, resulting in high titers of anti-CCP antibodies that are not usually present in other inflammatory conditions. Thus, anti-CCP antibodies have a high specificity for RA. Antibodies to citrullinated peptides/proteins are usually measured by enzyme-linked immunosorbent assay (ELISA) using a mixture of CCPs as the antigen. (Choice A) Anticentromere antibodies are found in the majority of patients with CREST syndrome. (Choice C) Antibodies to double-stranded DNA (anti-dsDNA) are specific for systemic lupus erythematosus. (Choice D) Rheumatoid factors are autoantibodies targeting the Fc portion of human IgG that occur in most patients with RA. Their diagnostic utility is limited by their poor specificity as they are found in approximately 10% of healthy individuals, in 30% of patients with systemic lupus erythematosus, and in nearly all patients with mixed cryoglobulinemia. (Choice E) The presence of antinuclear antibodies (ANA) is a nonspecific finding in many connective tissue disorders. Antinuclear antibodies characteristically occur in IgM form in patients with RA, but they are found less frequently than rheumatoid factors. (Choice F) Antiphospholipid antibodies are found in patients with systemic lupus erythematosus and antiphospholipid antibody syndrome. Antiphospholipid antibody syndrome causes hypercoagulability, paradoxical partial thromboplastin time (PTT) prolongation, and recurrent miscarriages (spontaneous abortions). Educational objective: Rheumatoid arthritis is characterized by symmetric polyarthritis (involving the metacarpophalangeal and proximal interphalangeal joints) with prolonged morning stiffness and associated fatigue. Antibodies to citrullinated peptides/proteins have a high specificity for the condition.

A 47-Year-Old Woman Comes to the Physician with Progressive Joint