Immunodeficiency with factor H anomaly

Immunodeficiency with factor H anomaly (also referred to as immunodeficiency due to complement factor H deficiency or factor H deficiency) is a rare primary immunodeficiency disorder caused by deficiency or dysfunction of complement factor H, a key regulatory protein of the alternative complement pathway. Factor H normally acts as a critical inhibitor that prevents excessive activation of the complement system against the body's own tissues. When factor H is absent or dysfunctional, uncontrolled complement activation leads to consumption of complement component C3 and other downstream factors, resulting in a secondary complement deficiency state. This condition primarily affects the immune system and the kidneys. Patients typically present with recurrent and severe bacterial infections, particularly with encapsulated organisms such as Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae, due to impaired opsonization and bacterial killing. A significant proportion of affected individuals also develop renal complications, including membranoproliferative glomerulonephritis (MPGN) or atypical hemolytic uremic syndrome (aHUS), as unregulated complement activation damages the glomerular endothelium and basement membrane. Laboratory findings characteristically show markedly reduced serum C3 levels with normal C4 levels, reflecting selective activation of the alternative pathway. Management is primarily supportive and includes prompt and aggressive treatment of infections with appropriate antibiotics, vaccination against encapsulated bacteria, and prophylactic antibiotics in some cases. Renal complications may require specific interventions including plasma infusion or plasma exchange to temporarily replace functional factor H. In cases progressing to end-stage renal disease, kidney transplantation may be considered, though disease recurrence in the graft is a recognized risk. More recently, complement-targeted therapies such as eculizumab have been used in some patients, particularly those with aHUS phenotype.

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