Complement Deficiencies

ADLI ALI*, FLORENCE BAKON**
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Complement Deficiencies and Associated Infections
There is wide variation of infections associated with complement deficiency depending on which complement protein and activation pathway is affected(Skattum et al 2011). Some complement deficiencies caries risk of infection, other mainly associated with autoimmune diseases. Some genetic and molecular defects has been identified to be associated complement deficiencies. The deficiencies in alternative pathway and terminal pathway is commonly presented with markedly increased susceptibility to Neisserial infections. Properdin deficiency (PD) has been reported in cases of severe meningococcal infections (Fijen et al 1999), recurrent otitis media and pneumonia (Schejbel et al 2009). PD has been identified as X-linked inheritance. Around 500 published cases of PD with Neisserial infections world wide. Neisserial meningitidis meningitis and Streptococcal Pneumonie also has been reported in complete Factor D deficiency. The TP components deficiencies has been reported association with Neisserial infection. Deficiency of C5, C6, C7 and C8 has less than 1000 reported cases of Neisserial meningitis and sepsis, while C9 deficiencies is more common in Japanese populations with prevalence around 1:1000 ( Fukumori et al 1989)(Nagata et al 1989). In LP,MBL deficiencies has been linked to cause recurrent infection in children(super et al, 1989). Around 10- 15% of Caucasian carries MBL gene that shows deficient concentration of functional MBL. Other rare deficiency MASP- deficiency, which reported in an adult with autoimmune symptoms and recurrent respiratory infections ( Stengaard-Pedersen 2003) and Ficolin-3 deficiency has been described in patient with recurrent respiratory infection and cerebral abscess ( Munthe-Fog et al). Increased susceptibility to encapsulated bacteria, S. pneumonia and N. meningitidis a common feature of CP deficiencies. CP deficiciency also associated with autoimmune disorders, like systemic lupus erythematosus. Few identified genetic determined deficiencies are C2D, C1q and C4 (Truedsson et al and Sjoholm et al ). C2D associated with abnormalities in serum immunoglobulin levels and associated with invasive encapsulated bacteria infection and autoimmune disease (Jonsson et al ). Other uncommon deficiencies suach as factor H deficiency, factor I deficiency which associated with susceptibility to encapsulated bacteria along with auto immune diseases such as glomerulonephritis ans vasculitis (Nilsson et al, Nita et al). C1 INH deficiency with prevalence of approximately 1 in 50 000 presents as hereditary angioedema. Complement deficiencies and associated genetic disorders and clinical manifestations is summarized in Table 1.

Table 1 - Complement deficiencies and clinical associations.
Proteins Genetics Frequency Infections Other associations
C1q Autosomal recessive 50 - 100 Sepsis, meningitis, pneumonia,
Streptococcus (S) pneumonia, Neisseria meningitidis
SLE
Cr1/C1s Autosomal recessive <20 Encapsulated bacteria pneumonia, meningitis SLE
C4 Autosomal recessive 20 -50 Sepsis, meningitis, pneumonia,
Streptococcus (S) pneumonia, Neisseria meningitidis
SLE
C2 Autosomal recessive 1/20 000 S.pneumonia, staphylococcus aureus, H. Influenza SLE
C3 Autosomal recessive 20-50 Respiratory tract infection, meningitis Immune-complex disease
Factor D Autosomal recessive <50 Meningitis, sepsis due to neisseria  
Properdin X-linked 100-500 Meningitis, sepsis due to neisseria  
MBL Common polymorphism in exon 1 5-15% of Caucasian Respiratory infection cardiovascular
MASP-2 Autosomal recessive <20 Respiratory infection autoimmune
Ficolin 3(H-ficolin) Autosomal recessive 1 Respiratory infection
Cerebral abscess, Streptococci. H influenza. Pseudomonas aeroginosa
thrombocytopenia
C5 Autosomal recessive 20-50 Meningitis due to neisseria  
C6 Autosomal recessive 50-100 Meningitis due to neisseria  
C7 Autosomal recessive 50-100 Meningitis due to neisseria  
C8 Autosomal recessive 50-100 Meningitis due to neisseria  
C9 Autosomal recessive 1/1000 in Japanese Meningitis due to neisseria  
Factor H Autosomal recessive <50 Recurrent pyogenic infections N.meningitidis, H influenzae Membrano proliferative glomerulonephritis, HUS
Factor I Autosomal recessive 5% Caucasian Recurrent pyogenic infections N.meningitidis, H influenzae Immune complex related disease
C1-INH Autosomal dominant 1/50000   HAE
CD59, CD55 Somatic mutations of PIG-A 1-2/1,000,000 Cytopenias Thrombosis, hematopoetic cytopenia
CR3/CD4 (LAD 1) Autosomal recessive 1/1,000,000 S. aureus, Gram-negative bacteria  



References
Complement Deficiencies Complement Deficiencies 02/19/2016
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