Complement deficiency is an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins.[4] Because of redundancies in the immune system, many complement disorders are never diagnosed. Some studies estimate that less than 10% are identified.[5]Hypocomplementemia may be used more generally to refer to decreased complement levels,[6] while secondary complement disorder means decreased complement levels that are not directly due to a genetic cause but secondary to another medical condition.[7]
Types
Disorders of the proteins that act to inhibit the complement system (such as C1-inhibitor) can lead to an overactive response, causing conditions such as hereditary angioedema.[8]
Disorders of the proteins that act to activate the complement system (such as C3) can lead to an underactive response, causing greater susceptibility to infections.[9]
Signs and symptoms
The following symptoms (signs) are consistent with complement deficiency in general:[1][3][10]
Deficiencies of the terminal complement components increases susceptibility to infections by Neisseria.[11]
Causes
The cause of complement deficiency is genetics (though cases of an acquired nature do exist post infection). The majority of complement deficiencies are inherited as autosomalrecessive conditions, while properdin deficiency occurs through X-linked inheritance. MBL deficiency can be inherited by either manner.[2]
Model of common structural genes and their possible contribution to the development of schizophrenia (as defined in the Sekar et al. article)
The mechanism of complement deficiency consists of:
C2: In regard to C2 deficiency, about 5 different mutations in the C2gene are responsible. In turn, immune function decreases and infection opportunities increase. One of the most common mutations deletes 28 DNA nucleotides from the C2 gene. Therefore, no C2 protein which can help make C3-convertase is produced. Ultimately, this delays/decreases immune response.[16]
C3: In terms of deficiency of C3, it has been found that 17 mutations in the C3 gene cause problems with C3. This rare condition mutates or prevents C3 protein from forming, lowering the immune system's ability to protect.[17]
In terms of management for complement deficiency, immunosuppressive therapy should be used depending on the disease presented. A C1-INH concentrate can be used for angio-oedema (C1-INH deficiency).[2][3]
^ abWinkelstein, Jerry A. (2004). "Complement Deficiencies". In Crocetti, Michael; Barone, Michael A. (eds.). Oski's Essential Pediatrics (2nd ed.). Philadelphia: Lippincott Williams & Wilkins. p. 670. ISBN9780781737708. Archived from the original on 12 January 2023. Retrieved 21 September 2016.
^Winkelstein, Jerry A. (2004). "The Complement System". In Gorbach, Sherwood L.; Bartlett, John G.; Blacklow, Neil R. (eds.). Infectious Diseases. Lippincott Williams & Wilkins. pp. 8–13. ISBN978-0-7817-3371-7.
^Sjöholm, A.G.; Jönsson, G.; Braconier, J.H.; Sturfelt, G.; Truedsson, L. (2006). "Complement deficiency and disease: An update". Molecular Immunology. 43 (1–2): 78–85. doi:10.1016/j.molimm.2005.06.025. PMID16026838.
Sullivan, Kathleen; Eibl, Martha M.; Erdős, Melinda; Maródi, László; Wolf, Hermann M.; Mahmoudi, Maryam; Rezaei, Nima (2012). "Complement Deficiencies". Clinical Cases in Primary Immunodeficiency Diseases. pp. 325–341. doi:10.1007/978-3-642-31785-9_8. ISBN978-3-642-31784-2.
