Rheumatoid Arthritis

5. A 41-year-old woman comes in for a checkup. You diagnosed her with rheumatoid
arthritis (RA) several
years ago when she presented with bilateral metacarpophalangeal joint swelling
with stiffness and
fatigue. The course of this patients disease has been mild, and the patient has
been maintained on nonsteroidal anti-inflammatory drugs (NSAIDs) and methotrexate therapy. Today she is
doing well; she has
minimal pain and functional impairment. She asks you about the cause of RA. This
stimulates you to
read about current evidence regarding the pathogenesis of this illness.
Which of the following statements regarding the pathogenesis of RA is false?
A. Damage to bone and cartilage by synovial tissue and pannus is mediated by several families of enzymes, including serine proteases and
B. IgG rheumatoid factor is most commonly detected in patients with RA
C. Interaction of rheumatoid factors with normal IgG activates complement and thereby starts a chain of events that includes production of
anaphylatoxins and chemotactic factors
D. Although many cytokines are involved in the pathogenesis of RA,
tumor necrosis factor (TNF-) and interleukin-1 (IL-1) are major
pathogenic factors
Key Concept/Objective: To understand the pathogenesis of RA
Damage to bone and cartilage by synovial tissue and pannus is mediated by several
families of enzymes, including serine proteases and cathepsins. The most damaging
enzymes
are the metalloproteinases (e.g., collagenase, stromelysin, and gelatinase) and
cathepsins

(especially cathepsin K), which can degrade the major structural proteins in the
joint. IgM
rheumatoid factor is most commonly detected; IgG and, less frequently, IgA
rheumatoid
factors are also sometimes found. The presence of IgG rheumatoid factor is
associated with
a higher rate of systemic complications (e.g., necrotizing vasculitis). Interaction of
rheumatoid factors with normal IgG activates complement and thereby starts a
chain of
events that includes production of anaphylatoxins and chemotactic factors.
Macrophageand fibroblast-derived cytokines (e.g., IL-1, IL-6, TNF-, and granulocytemacrophage
colony-stimulating factor) are abundantly expressed in the rheumatoid joint.
Although
many of these cytokines are involved in the pathogenesis of RA, TNF- and IL-1 are
major
pathogenic factors; both can induce synoviocyte proliferation, collagenase
production,
and prostaglandin release. (Answer: BIgG rheumatoid factor is most commonly
detected in
patients with RA)