H00104 | |
H number | H00104 |
Name | Alternative complement pathway component defects |
Description | The alternative pathway (AP) is antibody independent and relies on native C3 undergoing minimal spontaneous hydrolysis. Hydrolyzed C3 binds factor B. Factor B, when bound to hydrolyzed C3, is cleaved by factor D into Ba and Bb. Hydrolyzed C3Bb is responsible for a constant low level of C3 cleavage into C3b. If C3b binds to an appropriate surface, factor B will bind with C3b to form C3bBb, a highly efficient C3-cleaving enzyme. This overall series of successive proteolytic steps is enhanced by the serum protein properdin, which stabilizes protein:protein interactions during the process. Factor H is essential in controlling the function of the alternative pathway by inhibiting the formation of and degrading C3bBb. Deficiencies of alternative pathway-specific components are rare, and usually lead to an increased frequency of Neisseria infections. |
Category | Primary immunodeficiency |
Network | nt06513 Complement cascade |
Gene | (CFBD) CFB [HSA:629] [KO:K01335] (CFDD) CFD [HSA:1675] [KO:K01334] (CFHD) CFH [HSA:3075] [KO:K04004] (CFPD) CFP [HSA:5199] [KO:K15412] |
Pathogen | - |
Env factor | - |
Carcinogen | - |
Drug | - |
Comment | - |
Other DBs | ICD-11: 4A00.1 OMIM: 615561 613912 609814 312060 |
Reference | PMID:19758139 AUTHORS Pettigrew HD, Teuber SS, Gershwin ME TITLE Clinical significance of complement deficiencies. JOURNAL Ann N Y Acad Sci 1173:108-23 (2009) DOI:10.1111/j.1749-6632.2009.04633.x PMID:17162365 AUTHORS Kumar A, Teuber SS, Gershwin ME. TITLE Current perspectives on primary immunodeficiency diseases. JOURNAL Clin Dev Immunol 13:223-59 (2006) DOI:10.1080/17402520600800705 PMID:17952897 AUTHORS Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, Hammarstrom L, Nonoyama S, Ochs HD, Puck JM, Roifman C, Seger R, Wedgwood J. TITLE Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. JOURNAL J Allergy Clin Immunol 120:776-94 (2007) DOI:10.1016/j.jaci.2007.08.053 PMID:24152280 (CFBD) AUTHORS Slade C, Bosco J, Unglik G, Bleasel K, Nagel M, Winship I TITLE Deficiency in complement factor B. JOURNAL N Engl J Med 369:1667-9 (2013) DOI:10.1056/NEJMc1306326 PMID:11457876 (CFDD) AUTHORS Biesma DH, Hannema AJ, van Velzen-Blad H, Mulder L, van Zwieten R, Kluijt I, Roos D TITLE A family with complement factor D deficiency. JOURNAL J Clin Invest 108:233-40 (2001) DOI:10.1172/JCI12023 PMID:9312129 (CFHD) AUTHORS Ault BH, Schmidt BZ, Fowler NL, Kashtan CE, Ahmed AE, Vogt BA, Colten HR TITLE Human factor H deficiency. Mutations in framework cysteine residues and block in H protein secretion and intracellular catabolism. JOURNAL J Biol Chem 272:25168-75 (1997) DOI:10.1074/jbc.272.40.25168 PMID:8530058 (CFPD) AUTHORS Westberg J, Fredrikson GN, Truedsson L, Sjoholm AG, Uhlen M TITLE Sequence-based analysis of properdin deficiency: identification of point mutations in two phenotypic forms of an X-linked immunodeficiency. JOURNAL Genomics 29:1-8 (1995) DOI:10.1006/geno.1995.1208 |