Factor B Deficiency of Alternative Pathway

Factor D Deficiency of Alternative Pathway Related Products

Factor B Deficiency of Alternative Pathway Background

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.

Factor B Deficiency of Alternative Pathway References

1. Pettigrew H D, et al. (2009). Clinical significance of complement deficiencies. Annals of the New York Academy of Sciences, 1173(1), 108-123.
2. Slade C, et al. (2013). Deficiency in complement factor B. New England Journal of Medicine, 369(17), 1667-1669.
3. Klein R J, et al. (2005). Complement factor H polymorphism in age-related macular degeneration. Science, 308(5720), 385-389.
4. Botto M. (1999). C1q knock-out mice for the study of complement deficiency in autoimmune disease. Experimental and clinical immunogenetics, 15(4), 231-234.
5. Sjöholm A G, et al. (2006). Complement deficiency and disease: an update. Molecular immunology, 43(1), 78-85.