Curr Opin Immunol. 2025 Dec 19;98:102711. doi: 10.1016/j.coi.2025.102711. Online ahead of print.

ABSTRACT

The complement system is a central component of innate immunity, mediating opsonization, chemotaxis, cytolysis, and shaping adaptive responses. Deficiencies in complement proteins, whether inherited or acquired, predispose to severe infections, particularly with encapsulated bacteria such as Neisseria meningitidis and Streptococcus pneumoniae. Although rare, inherited defects affect different pathways and may also present with autoimmune or renal diseases. Diagnosis relies on functional and quantitative assays, especially in patients with early-onset or recurrent infections. Complement inhibition, introduced with eculizumab and expanded to agents targeting C3, Factor B, or Factor D, has transformed the management of complement-mediated disorders but unmasked novel infectious risks, including meningococcal disease and invasive fungal infections. This review summarizes clinical and mechanistic aspects of complement deficiencies, infection risks associated with therapeutic blockade, and current diagnostic strategies. It emphasizes the importance of anticipatory care, vaccination, and prophylaxis as new complement-targeted drugs continue to emerge.

PMID:41421099 | DOI:10.1016/j.coi.2025.102711