A 10-year-old boy is brought to the emergency department by his parents due to increasing lethargy and high fever for the past 12 hours. The boy was well last night but was sluggish this morning. Over the day, his activity level and responsiveness diminished. The patient was treated for Neisseria meningitidis bacteremia 2 years ago. He has received all routine vaccinations and is developing normally. Temperature is 39.6 C (103.3 F) . On examination, the patient appears ill and is poorly responsive. He is tachycardic, but heart sounds are otherwise unremarkable. Lungs are clear to auscultation. Numerous purple bruise-like markings and petechiae are noted over his extremities, which have diminished capillary refill. Blood samples are drawn for total complement (CH50) and alternative complement (AH50) measurement. Which of the following sets of results is most likely to be found in this patient?

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11ec160b_37a6_c403_9249_c12543a52aed_MD0001_00 This boy's rapidly progressive illness with high fever and petechial rash raises strong suspicion for Neisseria meningitidis infection. The virulence of N meningitidis is due to the presence of a polysaccharide capsule, which allows the organism to evade phagocytosis and immunoglobulin attachment. Because of these adaptations, initial control of infection is primarily mediated by activation of the alternative complement cascade, which is triggered when autoactivated C3 interacts with the surface of the bacteria and amplifies. Activation of the alternative pathway results in generation of the following: C3b: a powerful opsonin that binds to complement receptor 1 on erythrocytes and phagocytes, which increases phagocytosis by reticuloendothelial monocytes C3a and C5a: potent anaphylatoxins that recruit immune cells and drive a strong inflammatory response Membrane attack complexes (MACs): composed of the terminal complement proteins (C5-9), MACs generate a channel in the bacterial surface, leading to osmotic lysis of the organism MACs are the most important initial defense against encapsulated bacteria because they operate at high efficiency despite the presence of a capsule. Therefore, patients with deficits in any of the terminal complement proteins that generate the MAC are at very high risk for recurrent encapsulated bacterial infections (as seen in this patient). Laboratory evaluation of these patients will show reduced activity of the classical (CH50) and alternative (AH50) complement cascades because all 3 complement pathways (classical, alternative, lectin) terminate in the generation of MACs. (Choices B and C) Deficiency in complement proteins unique to the classical cascade (eg, C1q/r/s, C2, C4) will result in low CH50 and normal AH50 levels. In contrast, deficiency in complement proteins unique to the alternative cascade (eg, factor B, factor D) will result in normal CH50 and low AH50 levels. This patient's recurrent N meningitidis infections are more characteristic of a terminal complement component deficiency. (Choice D) Patients with a defect in the lectin complement pathway (eg, mannose-binding lectin) will have normal CH50 and AH50 levels. Additional evaluation with the mannose-binding lectin test can usually reveal the presence of this abnormality. Educational objective: Initial control of encapsulated bacteria is largely reliant on the formation of membrane attack complexes (MACs) due to activation of the alternative complement cascade. Patients with deficiency in the proteins that generate MACs (C5-9) are at high risk for recurrent encapsulated bacterial infection; evaluation will show reduced activity of the classical (CH50) and alternative (AH50) complement cascades.

A 10-Year-Old Boy Is Brought to the Emergency Department by His