C1 inhibitor deficiency (hereditary angioedema) C4 binding protein alpha deficiency C4 binding protein beta deficiency Factor I deficiency Decay-accelerating factor (CD55) deficiency CD59 deficiency
Supergrp
Disorders of innate immunity [DS:H02525] Primary immunodeficiency disease [DS:H01725]
Description
To prevent undesirable complement activation, host tissues express a number of complement regulatory proteins (CRPs). They include C1 inhibitor (C1-INH, also termed SERPING1), C4 binding protein (C4BP), Factor I, decay accelerating factor (DAF), CD59, and so on. C1-INH (SERPING1) deficiency can be genetic or acquired, and this causes an episodic, local increase in vascular permeability in the subcutaneous and submucosal layers, identified as angioedema (hereditary or acquired). Genetic deficiency of C4BP has only been reported in one individual who developed an illness with similarities to Behcet's syndrome. Heterozygous mutations within the Factor I gene have been recently identified in individuals with atypical hemolytic uremic syndrome (aHUS), while homozygous deficiency of Factor I is an unusual feature. Factor I-deficient patients present high susceptibility to respiratory tract infections and meningitis. Kidney impairment and autoimmune disorders have also been observed. Only a single case of CD59 deficiency has been reported and this individual developed a paroxysmal nocturnal haemoglobinuria(PNH)-like illness. In contrast, deficiency of DAF is not associated with haemolytic anaemia.
Category
Primary immunodeficiency
Brite
Human diseases in ICD-11 classification [BR:br08403]
04 Diseases of the immune system
Primary immunodeficiencies
4A00 Primary immunodeficiencies due to disorders of innate immunity
H00106 Complement regulatory protein defects
Pathway-based classification of diseases [BR:br08402]
Immune system
nt06513 Complement cascade
H00106 Complement regulatory protein defects
nt06514 Coagulation cascade
H00106 Complement regulatory protein defects
Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee.
C3 glomerulopathy (C3G) describes a pathologic pattern of injury diagnosed by renal biopsy characterized by the dominant deposition of the third component of complement (C3) in the renal glomerulus. Autoantibodies to the C3 and C5 convertases of complement are the most commonly detected drivers of complement dysregulation, although genetic mutations in complement genes can also be found.
Category
Immune system disease; Urinary system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
21 Symptoms, signs or clinical findings, not elsewhere classified
Symptoms, signs or clinical findings of the genitourinary system
Clinical findings in specimens from the urinary system
MF8Y Other specified clinical findings in specimens from the urinary system
H02579 C3 glomerulopathy
Pathway-based classification of diseases [BR:br08402]
Immune system
nt06513 Complement cascade
H02579 C3 glomerulopathy
Gale DP, de Jorge EG, Cook HT, Martinez-Barricarte R, Hadjisavvas A, McLean AG, Pusey CD, Pierides A, Kyriacou K, Athanasiou Y, Voskarides K, Deltas C, Palmer A, Fremeaux-Bacchi V, de Cordoba SR, Maxwell PH, Pickering MC
Title
Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis.
Macular degeneration is the physical breakdown of the central portion of the retina called the macula. Age-related macular degeneration (AMD/ARMD) is the leading cause of blindness. AMD is a complex disease caused by the combination of genetic predisposition and environmental factors. Using genome linkage scan and association studies, multiple potentially causative genes have been identified. In AMD, there are two phenotypes, atrophic/ dry and neovascular/ wet. The former is characterized by the geographic atrophy due to death of retinal pigment epithelium, and the latter is usually characterized by the abnormal growth of new blood vessels under the macula, which causes severe loss of vision. While wet AMD can be treated by the inhibition of vascular endothelial growth factor or photodynamic therapy, so far there are no available treatments for dry AMD.
Category
Nervous system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
09 Diseases of the visual system
Disorders of the eyeball posterior segment
Disorders of the retina
9B75 Macular disorders
H00821 Age-related macular degeneration
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06535 Efferocytosis
H00821 Age-related macular degeneration
nt06527 Necroptosis
H00821 Age-related macular degeneration
Immune system
nt06513 Complement cascade
H00821 Age-related macular degeneration
nt06517 TLR signaling
H00821 Age-related macular degeneration
Schultz DW, Klein ML, Humpert AJ, Luzier CW, Persun V, Schain M, Mahan A, Runckel C, Cassera M, Vittal V, Doyle TM, Martin TM, Weleber RG, Francis PJ, Acott TS
Title
Analysis of the ARMD1 locus: evidence that a mutation in HEMICENTIN-1 is associated with age-related macular degeneration in a large family.
Rivera A, Fisher SA, Fritsche LG, Keilhauer CN, Lichtner P, Meitinger T, Weber BH
Title
Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk.
Zareparsi S, Buraczynska M, Branham KE, Shah S, Eng D, Li M, Pawar H, Yashar BM, Moroi SE, Lichter PR, Petty HR, Richards JE, Abecasis GR, Elner VM, Swaroop A
Title
Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration.
Seddon JM, Yu Y, Miller EC, Reynolds R, Tan PL, Gowrisankar S, Goldstein JI, Triebwasser M, Anderson HE, Zerbib J, Kavanagh D, Souied E, Katsanis N, Daly MJ, Atkinson JP, Raychaudhuri S
Title
Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.
The haemolytic uraemic syndrome (HUS) is characterized by the triad of thrombocytopenia, microangiopathic haemolytic anaemia and acute renal failure. HUS may be classified as either diarrhoeal-associated (D+HUS) or non-diarrhoeal/atypical (aHUS). Approximately half of the patients with aHUS have mutations in genes that regulate the complement system. Several other conditions and factors, such as infection, drugs, pregnancy, and malignancy, have been reported to cause aHUS.
Category
Hematologic disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
03 Diseases of the blood or blood-forming organs
Anaemias or other erythrocyte disorders
Haemolytic anaemias
Congenital haemolytic anaemia
3A10 Hereditary haemolytic anaemia
H01434 Atypical hemolytic uremic syndrome
Pathway-based classification of diseases [BR:br08402]
Immune system
nt06513 Complement cascade
H01434 Atypical hemolytic uremic syndrome
Goicoechea de Jorge E, Harris CL, Esparza-Gordillo J, Carreras L, Arranz EA, Garrido CA, Lopez-Trascasa M, Sanchez-Corral P, Morgan BP, Rodriguez de Cordoba S
Title
Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome.
