Serum sickness can occur after administration of which type of therapeutic agents?

• A. Bacterial toxins
• B. Vaccines with inactivated pathogens
• C. Small molecule drugs
• D. Non-human proteins such as monoclonal antibodies derived from non-human sources

Answer: (D)

Serum sickness is an immune complex–mediated (type III) hypersensitivity that occurs when the body mounts an antibody response against a foreign protein present in a therapeutic agent. The resulting immune complexes form and deposit in tissues, activating complement and causing inflammation. This pattern is most likely with non-human proteins introduced into the body, such as monoclonal antibodies derived from non-human sources or animal-derived antisera.

Because these foreign proteins are recognized as non-self, antibodies form against them, leading to fever, rash, joint pains, and sometimes kidney involvement days to weeks after exposure. In contrast, bacterial toxins are toxins rather than proteins from a foreign immune repertoire, vaccines with inactivated pathogens are designed to elicit protective immunity with lower risk of this immune-complex reaction, and small molecule drugs are typically not proteins and do not usually produce this immune complex–driven syndrome. Therefore, non-human proteins such as monoclonal antibodies from non-human sources are the classic culprits.