Complement Factor I (CFI) deficiency

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Overview

Complement Factor I (CFI) deficiency is a rare genetic disorder affecting the immune system, specifically the complement system. Individuals with CFI deficiency are prone to recurrent infections, particularly those caused by encapsulated bacteria like Neisseria meningitidis and Streptococcus pneumoniae. In addition to infections, some individuals may also experience autoimmune or inflammatory conditions, including glomerulonephritis with isolated C3 deposits, rheumatoid arthritis, or systemic lupus erythematosus. 

CFI deficiency is caused by mutations in the CFI gene, which provides instructions for making the CFI protein. 

Impact on the Complement System:
The CFI protein is a crucial regulator of the complement system, an important part of the innate immune response. It helps control the activation and amplification of the complement cascade, preventing excessive inflammation and tissue damage. 

Infections:
CFI deficiency leads to impaired complement-mediated opsonization and pathogen clearance, making individuals more susceptible to infections, especially those caused by encapsulated bacteria. 

Autoimmune/Inflammatory Conditions:
Defective CFI function can also lead to dysregulation of the immune system, potentially contributing to autoimmune and inflammatory diseases

Symptoms

Individuals with CFI deficiency often experience recurrent bacterial infections, including those of the upper respiratory tract, ears, skin, and urinary tract. More severe infections like pneumonia, meningitis, and sepsis can also occur. Beyond infections, other symptoms can include kidney disorders (glomerulonephritis) and autoimmune disorders like rheumatoid arthritis and systemic lupus erythematosus (SLE)

Causes

Complement Factor I (CFI) deficiency is primarily caused by mutations in the CFI gene, which provides instructions for making the CFI protein, an essential regulator of the complement system. These mutations lead to a deficiency or dysfunction of the CFI protein, causing uncontrolled activation of the complement system. This dysregulation can result in various health problems, including increased susceptibility to infections, autoimmune disorders, and kidney disease. 

Prevention

While there’s no cure, preventative measures focus on managing infections and reducing the risk of complications. 

Diagnosis

Complement Factor I (CFI) deficiency is diagnosed through a combination of clinical evaluation, laboratory testing, and genetic analysis. Suspect CFI deficiency in individuals with recurrent infections, particularly those caused by encapsulated bacteria, or with certain autoimmune or rheumatological conditions. Laboratory tests assess complement protein levels and function, while genetic testing identifies mutations in the CFI gene.

Prognosis

Complement Factor I (CFI) deficiency has a varied prognosis depending on whether it’s a complete or partial deficiency. Complete deficiencies, often due to homozygous or compound heterozygous mutations, are associated with a higher risk of severe infections (especially from encapsulated bacteria), autoimmune and inflammatory disorders, and potential neurological complications. Partial deficiencies, often linked to heterozygous mutations, may be associated with atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration

Treatment

Complement Factor I (CFI) deficiency, a rare genetic condition, is treated by managing its associated complications, primarily infections and immune system dysregulation. Treatment strategies include: preventing and treating infections with antibiotics and vaccinations, managing immune-related inflammation with corticosteroids or immunosuppressants, and potentially using therapies that target the complement system, like eculizumab.