Complement deficiency

Complement pathway (normal)
Symptoms| Recurring infection, rheumatic disease[1]
Causes| Can be inherited or acquired[2]
Diagnostic method| CH50 measurement, Plasma level[3]
Treatment| Immunosuppressive therapy[2]

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]

## Contents

* 1 Types
* 2 Signs and symptoms
* 2.1 Complications
* 3 Causes
* 3.1 Inherited
* 3.2 Acquired
* 4 Mechanism
* 5 Diagnosis
* 6 Treatment
* 7 Epidemiology
* 8 See also
* 9 References
* 10 Further reading
* 11 External links

## 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]

* Recurring infection
* Auto-immune disorders
* Glomerulonephritis
* Joint problems (manifestation)
* Lung function (MBL variant alleles)
* Angioedema
* Dermatomyositis
* Vasculitis
* Anaphylactoid purpura

### Complications

File:Neisseria-meningitidis-Differentially-Controls-Host-Cell-Motility-through-PilC1-and-PilC2-pone.0006834.s003.ogv

Vaccinations for encapsulated organisms (e.g., Neisseria meningitidis and Streptococcus pneumoniae) is crucial for preventing infections in complement deficiencies. Among the possible complications are the following:

* 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 autosomal recessive conditions, while properdin deficiency occurs through X-linked inheritance. MBL deficiency can be inherited by either manner.[2]

### Inherited

* Properdin deficiency is an X-linked[12] disorder that also causes susceptibility to Neisseria infections.[2]
* C1-inhibitor deficiency or hereditary angioedema will have low C4 with normal C1 levels.[13]

### Acquired

Acquired hypocomplementemia may occur in the setting of bone infections (osteomyelitis), infection of the lining of the heart (endocarditis), and cryoglobulinemia. Systemic lupus erythematosus is associated with low C3 and C4.[14] Membranoproliferative glomerulonephritis usually has low C3.[15]

## Mechanism

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 C2 gene 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]
* C4: C4 deficiency is highly associated with systemic lupus erythematosus.[3] Aβ42, a protein involved in Alzheimer's disease, can cause activation of C4 (even in plasma deficient of C1q).[18] At least one study indicates that the genetic variation of C4 plays a role in schizophrenia.[19]

## Diagnosis

Template:Complement test comparisons The diagnostic tests used to diagnose a complement deficiency include:[3]

* CH50 measurement
* Immunochemical methods/test
* C3 deficiency screening
* Mannose-binding lectin (lab study)
* Plasma levels/regulatory proteins (lab study)

## Treatment

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]

Pneumococcus and Haemophilus infections can be prevented via immunization.[2] Epsilon-aminocaproic acid could be used to treat hereditary C1-INH deficiency, though the possible side effect of intravascular thrombosis should be weighed.[7]

## Epidemiology

C2 deficiency has a prevalence of 1 in about 20,000 people in Western countries.[2]

## See also

* Paroxysmal nocturnal hemoglobinuria

## References

1. ↑ 1.0 1.1 Winkelstein, Jerry A. (2004). "Complement Deficiencies". in Crocetti, Michael (in en). Oski's Essential Pediatrics (2nd ed.). Philadelphia: Lippincott Williams & Wilkins. p. 670. ISBN 9780781737708. https://books.google.com/books?id=I3Kh1cNJxyUC&q=complement+deficiency&pg=PA670. Retrieved 21 September 2016.
2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 "Complement Deficiencies. What are complement deficiencies?" (in en-GB). https://patient.info/doctor/complement-deficiencies.
3. ↑ 3.0 3.1 3.2 3.3 3.4 "Complement Deficiencies Clinical Presentation: History, Physical, Causes". http://emedicine.medscape.com/article/135478-clinical#showall.
4. ↑ Winkelstein, Jerry A. (2004). "The Complement System". in Gorbach, Sherwood L.. Infectious Diseases. Lippincott Williams & Wilkins. pp. 8–13. ISBN 978-0-7817-3371-7.
5. ↑ 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. PMID 16026838.
6. ↑ Moreland, Larry W., ed (2004). "Hypocomplementemia". Rheumatology and Immunology Therapy. p. 425. doi:10.1007/3-540-29662-X_1306. ISBN 3-540-20625-6. https://books.google.com/books?id=GiR493YLsgsC&pg=PA425.
7. ↑ 7.0 7.1 Complement-Related Disorders at eMedicine
8. ↑ Davis, Alvin E.; Mejia, Pedro; Lu, Fengxin (1 October 2008). "Biological activities of C1 inhibitor". Molecular Immunology 45 (16): 4057–4063. doi:10.1016/j.molimm.2008.06.028. PMID 18674818.
9. ↑ Ram, S.; Lewis, L. A.; Rice, P. A. (7 October 2010). "Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy". Clinical Microbiology Reviews 23 (4): 740–780. doi:10.1128/CMR.00048-09. PMID 20930072.
10. ↑ Pettigrew, H. David; Teuber, Suzanne S.; Gershwin, M. Eric (September 2009). "Clinical Significance of Complement Deficiencies". Annals of the New York Academy of Sciences 1173 (1): 108–123. doi:10.1111/j.1749-6632.2009.04633.x. PMID 19758139. Bibcode: 2009NYASA1173..108P.
11. ↑ Aghamohammadi, Asghar; Rezaei, Nima (13 December 2012) (in en). Clinical Cases in Primary Immunodeficiency Diseases: A Problem-Solving Approach. Springer Science & Business Media. p. 334. ISBN 978-3-642-31785-9. https://books.google.com/books?id=IftYOIDjQbcC&q=terminal+complement+components+Neisseria.&pg=PA334. Retrieved 30 January 2022.
12. ↑ "OMIM Entry - # 312060 - PROPERDIN DEFICIENCY, X-LINKED; CFPD". http://omim.org/entry/312060.
13. ↑ Gower, Richard G; Busse, Paula J; Aygören-Pürsün, Emel; Barakat, Amin J; Caballero, Teresa; Davis-Lorton, Mark; Farkas, Henriette; Hurewitz, David S et al. (15 February 2011). "Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies". The World Allergy Organization Journal 4 (Suppl 2): S9–S21. doi:10.1097/1939-4551-4-S2-S9. PMID 23283143.
14. ↑ "Systemic Lupus Erythematosus. Lupus treatment; information | Patient". http://patient.info/doctor/systemic-lupus-erythematosus-pro.
15. ↑ "Membranoproliferative Glomerulonephritis: Background, Pathophysiology, Etiology". http://emedicine.medscape.com/article/240056-overview.
16. ↑ Reference, Genetics Home. "C2 gene". https://medlineplus.gov/genetics/gene/c2/.
17. ↑ Reference, Genetics Home. "C3 gene". https://medlineplus.gov/genetics/gene/c3/.
18. ↑ Kolev, Martin V; Ruseva, Marieta M; Harris, Claire L; Morgan, B. Paul; Donev, Rossen M (1 March 2009). "Implication of Complement System and its Regulators in Alzheimer's Disease". Current Neuropharmacology 7 (1): 1–8. doi:10.2174/157015909787602805. PMID 19721814.
19. ↑ Sekar, Aswin; Bialas, Allison R.; de Rivera, Heather; Davis, Avery; Hammond, Timothy R.; Kamitaki, Nolan; Tooley, Katherine; Presumey, Jessy et al. (2016-02-11). "Schizophrenia risk from complex variation of complement component 4". Nature 530 (7589): 177–183. doi:10.1038/nature16549. PMID 26814963. Bibcode: 2016Natur.530..177..

## Further reading

* Botto, Marina (1 January 2001). "Links between complement deficiency and apoptosis". Arthritis Research & Therapy 3 (4): 207–210. doi:10.1186/ar301. PMID 11438036.
* 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. ISBN 978-3-642-31784-2.

## External links

Classification|

* ICD-10: D84.1
* ICD-9-CM: 279.8
* OMIM: 217000 Online Mendelian Inheritance in Man (OMIM) 120820, Online Mendelian Inheritance in Man (OMIM) 120900, Online Mendelian Inheritance in Man (OMIM) 610102
* DiseasesDB: 1847

|

External resources|

* eMedicine: med/419 ped/447

| Wikimedia Commons has media related to Complement deficiency.

|

| Scholia has a topic profile for Complement deficiency.

|

* v
* t
* e

Lymphoid and complement disorders causing immunodeficiency

Primary|

| Antibody/humoral
(B)|

| Hypogammaglobulinemia|

* X-linked agammaglobulinemia
* Transient hypogammaglobulinemia of infancy

|

Dysgammaglobulinemia|

* IgA deficiency
* IgG deficiency
* IgM deficiency
* Hyper IgM syndrome (1
* 2
* 3
* 4
* 5)
* Wiskott–Aldrich syndrome
* Hyper-IgE syndrome

Other|

* Common variable immunodeficiency
* ICF syndrome

T cell deficiency
(T)|

* thymic hypoplasia: hypoparathyroid (Di George's syndrome)
* euparathyroid (Nezelof syndrome
* Ataxia–telangiectasia)

peripheral: Purine nucleoside phosphorylase deficiency

* Hyper IgM syndrome (1)

Severe combined
(B+T)|

* x-linked: X-SCID
autosomal: Adenosine deaminase deficiency
* Omenn syndrome
* ZAP70 deficiency
* Bare lymphocyte syndrome

Acquired|

* HIV/AIDS

Leukopenia:
Lymphocytopenia|

* Idiopathic CD4+ lymphocytopenia

Complement
deficiency|

* C1-inhibitor (Angioedema/Hereditary angioedema)
* Complement 2 deficiency/Complement 4 deficiency
* MBL deficiency
* Properdin deficiency
* Complement 3 deficiency
* Terminal complement pathway deficiency
* Paroxysmal nocturnal hemoglobinuria
* Complement receptor deficiency

* v
* t
* e

Medicine

Specialties
and
subspecialties|

Surgery

* Cardiac surgery
* Cardiothoracic surgery
* Colorectal surgery
* Eye surgery
* General surgery
* Neurosurgery
* Oral and maxillofacial surgery
* [[[Medicine:Orthopedic surgery|Orthopedic surgery]]
* Hand surgery
* Otolaryngology
* ENT
* Pediatric surgery
* Plastic surgery
* Reproductive surgery
* Surgical oncology
* Thoracic surgery
* Transplant surgery
* Trauma surgery
* Urology
* Andrology
* Vascular surgery

Internal medicine

* Allergy / Immunology
* Angiology
* Cardiology
* Endocrinology
* Gastroenterology
* Hepatology
* Geriatrics
* Hematology
* Hospital medicine|
* Infectious disease
* Nephrology
* Oncology
* Pulmonology
* Rheumatology

Obstetrics and gynaecology

* Gynaecology
* Gynecologic oncology
* Maternal–fetal medicine
* Obstetrics
* Reproductive endocrinology and infertility
* Urogynecology

Diagnostic

* Radiology
* Interventional radiology
* Nuclear medicine
* Pathology
* Anatomical
* Clinical pathology
* Clinical chemistry
* Clinical immunology
* Cytopathology
* Medical microbiology
* Transfusion medicine

Other specialties

* Addiction medicine
* Adolescent medicine
* Anesthesiology
* Dermatology
* Disaster medicine
* Diving medicine
* Emergency medicine
* Mass gathering medicine
* Family medicine
* General practice
* Hospital medicine
* Intensive care medicine
* Medical genetics
* Narcology
* Neurology
* Clinical neurophysiology
* Occupational medicine
* Ophthalmology
* Oral medicine
* Pain management
* Palliative care
* Pediatrics
* Neonatology
* Physical medicine and rehabilitation
* PM&R
* Preventive medicine
* Psychiatry
* Addiction psychiatry
* Radiation oncology
* Reproductive medicine
* Sexual medicine
* Sleep medicine
* Sports medicine
* Transplantation medicine
* Tropical medicine
* Travel medicine
* Venereology

Medical education|

* Medical school
* Bachelor of Medicine, Bachelor of Surgery
* Bachelor of Medical Sciences
* Master of Medicine
* Master of Surgery
* Doctor of Medicine
* Doctor of Osteopathic Medicine
* MD–PhD

Related topics|

* Alternative medicine
* Allied health
* Dentistry
* Podiatry
* Physiotherapy
* Molecular oncology
* Nanomedicine
* Personalized medicine
* Public health
* Traditional medicine
* Veterinary medicine
* Physician
* Chief physician
* History of medicine

* Book
* Category
* Commons
* Wikiproject
* Portal
* Outline

0.00

(0 votes)

Original source: https://en.wikipedia.org/wiki/Complement deficiency. Read more

|

Retrieved from "https://handwiki.org/wiki/index.php?title=Medicine:Complement_deficiency&oldid=4016648"
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template