A 22-year-old woman comes to the emergency department with fevers and arthralgias. She recently had unprotected sexual intercourse with a new male partner. Her temperature is 38.4 C (101.1 F), blood pressure is 118/76 mm Hg, pulse is 102/min, and respirations are 16/min. Examination shows several pustules on the dorsal aspects of her forearms. Her right wrist and ankle are tender on palpation. Gram-negative bacteria isolated from this patient's blood produce an enzyme that splits the IgA molecule at the hinge region. Which of the following is likely to be the most important role of this bacterial enzyme in the course of the infection?

Question

A 22-year-old woman comes to the emergency department with fevers and arthralgias.  She recently had unprotected sexual intercourse with a new male partner.  Her temperature is 38.4 C (101.1 F), blood pressure is 118/76 mm Hg, pulse is 102/min, and respirations are 16/min.  Examination shows several pustules on the dorsal aspects of her forearms.  Her right wrist and ankle are tender on palpation.  Gram-negative bacteria isolated from this patient's blood produce an enzyme that splits the IgA molecule at the hinge region.  Which of the following is likely to be the most important role of this bacterial enzyme in the course of the infection?

Quizplus · Accepted Answer

This patient likely has disseminated gonorrheal infection (triad of arthritis, dermatitis, and tenosynovitis in a sexually active woman) due to Neisseria gonorrhoeae. In mucosal regions as well as in secretions, IgA exists in its secretory form, composed of an IgA dimer (joined by a peptide J chain) and a peptide secretory component. IgA antibodies usually bind to pili and other membrane proteins involved in bacterial adherence to mucosa, thus inhibiting mucosal colonization by the microorganism. Certain bacteria (eg, N gonorrhoeae, N meningitidis, Streptococcus pneumoniae, Haemophilus influenzae) produce IgA proteases that cleave IgA at its hinge region (yielding Fab and compromised Fc fragments), thus decreasing its effectiveness. This facilitates bacterial adherence to mucosa (possibly due to easier bacterial access to mucosal surface or immune disguise by binding to released Fab fragments, among others). (Choice B) IgA is a weak activator of the classic complement pathway. Impairment of complement-mediated cell lysis can be accomplished by staphylococcal protein A, which binds the Fc portion of IgG, preventing complement fixation. (Choice C) Although IgA Fc-mediated functions such as opsonization are compromised by IgA protease, secretory IgA is a poor opsonin. Impairment of opsonization and phagocytosis is most frequently accomplished by encapsulated bacteria such as S pneumoniae, N meningitidis, and H influenzae. (Choice D) IgA does not play a role in the induction of memory lymphocytes necessary for mounting a secondary immune response (which requires the formation of memory B and T lymphocytes after initial antigen exposure). (Choice E) Promotion of intracellular survival is accomplished by inhibition of phagosome-lysosome fusion or resistance to lysosomal enzymes. These properties are expressed by Mycobacterium tuberculosis, M leprae, Legionella, and Ehrlichia. Educational objective: IgA protease is produced by Neisseria meningitidis, N gonorrhoeae, Streptococcus pneumoniae, and Haemophilus influenzae. This enzyme cleaves secretory IgA at its hinge region, rendering it ineffective. Secretory IgA exists on mucosal surfaces and in secretions and acts to bind and inhibit the action of pili as well as other cell surface antigens that normally mediate mucosal adherence and subsequent penetration. __________ References: Working mechanism of immunoglobulin A1 (IgA1) protease: Cleavage of IgA1 antibody to Neisseria meningitidis porA requires de novo synthesis of IgA1 protease. (http://www.ncbi.nlm.nih.gov/pubmed/16177349)

A 22-Year-Old Woman Comes to the Emergency Department with Fevers