The alternative pathway of complement activation is antibody independent. Factor B, factor D, and properdin are required to stably initiate the process. The complex of factor B with hydrolyzed C3 is responsible for constant low-level cleavage of C3 into C3b. If C3b binds to an appropriate surface, factor B will bind with C3b to form C3bBb, a highly efficient C3-cleaving enzyme. There has only been one recorded case of factor B deficiency, and the individual presented with meningococcemia but no history of any autoimmune disorder.
Slade et al. described a 32-year-old woman with recurrent pneumococcal and meningococcal infection in whom factor B deficiency was detected. At 2 years of age, she had primary pneumococcal peritonitis. Two years later, she was treated for community-acquired pneumonia. At 15 years of age, meningitis (caused by Neisseria meningitidis, serogroup Y) developed. At age 30 years, pneumococcal pneumonia complicated by a unilateral empyema developed. She required prolonged admission to the intensive care unit for type 1 respiratory failure that prompted suspicion of an immunodeficiency, and she underwent a thoracotomy to drain the empyema.
Screening tests revealed normal immunoglobulins and lymphocyte subsets. Classical complement pathway activity was normal, but according to the results of a functional enzyme-linked immunosorbent assay (ELISA) (Wieslab, Euro Diagnostica), the alternative pathway was inactive.
Complement-mixing studies showed that the activity of the alternative pathway was restored to the patient's serum by properdin-deficient serum but not when the patient's serum was mixed with commercially sourced factor B–depleted serum. Factor B was undetectable by means of radial immunodiffusion (Binding Site) and ELISA (<36 g per liter; reference range, 119 to 245).
The patient received the tetravalent meningococcal vaccine and the 23-valent pneumococcal polysaccharide vaccine, as well as continuous prophylactic amoxicillin, and she has not had any further severe infections.
This novel case of factor B deficiency confirms the crucial role of factor B in activation of the alternative complement pathway and in protection against infection by encapsulated organisms.
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