Complement Deficiency

In a patient with recurrent invasive or unusually severe bacterial infection, obtain CH50 and AH50 concurrently as the initial complement screen. CH50 evaluates classical-pathway function and AH50 evaluates alternative-pathway function; abnormal results should drive targeted quantitative and functional assays rather than indiscriminate component testing. PubMed+2PubMedComplement Deficiency - StatPearls - NCBI BookshelfPubMedComplements and Their Role in Systemic DisordersPubMedBeyond Systemic Lupus Erythematosus and Anti-Phospholipid Syndrome: The Relevance of Complement From Pathogenesis to Pregnancy Outcome in Other Systemic Rheumatologic Diseases - PMC

Interpret a low CH50 with normal AH50 as a classical-pathway pattern. Quantify and, where indicated, assess function of C1, C2, C4, and C1 inhibitor. A low AH50 with normal CH50 instead directs evaluation of factor B, factor D, factor H, and factor I. PubMed+1PubMedComplement Deficiency - StatPearls - NCBI BookshelfPubMedComplements and Their Role in Systemic Disorders

If both CH50 and AH50 are low, prioritize evaluation of components shared by both pathways: C3 and terminal components C5, C6, C7, C8, and C9. If both assays are normal but recurrent infection still raises concern for a complement disorder, obtain an MBL functional assay or MBL measurement. PubMed+2PubMedComplement Deficiency - StatPearls - NCBI BookshelfPubMedComplements and Their Role in Systemic DisordersPubMedBeyond Systemic Lupus Erythematosus and Anti-Phospholipid Syndrome: The Relevance of Complement From Pathogenesis to Pregnancy Outcome in Other Systemic Rheumatologic Diseases - PMC

Early classical-pathway component deficiencies, including C1, C2, and C4 deficiency, are associated with infection by encapsulated bacteria, particularly Streptococcus pneumoniae and Haemophilus influenzae type b. In this phenotype, a low CH50 with preserved AH50 supports a classical-pathway defect and should trigger component confirmation. PubMedPubMedComplement Deficiency - StatPearls - NCBI Bookshelf

C3 deficiency is associated with severe recurrent pyogenic infections early in life. A pattern of both low CH50 and low AH50 is compatible with C3 or terminal-pathway deficiency, but component-level assays are required before assigning a specific diagnosis. PubMed+2PubMedComplement Deficiency - StatPearls - NCBI BookshelfPubMedComplements and Their Role in Systemic DisordersPubMedBeyond Systemic Lupus Erythematosus and Anti-Phospholipid Syndrome: The Relevance of Complement From Pathogenesis to Pregnancy Outcome in Other Systemic Rheumatologic Diseases - PMC

Do not label every abnormal functional assay as inherited deficiency. Complement abnormalities may be acquired through complement overconsumption, impaired protein synthesis, protein-loss disorders, autoimmunity, or high catabolic states. Reassess CH50/AH50 and component levels in the clinical context before interpreting a single abnormal result as a constitutional defect. PubMedPubMedComplement Deficiency - StatPearls - NCBI Bookshelf

For recurrent angioedema without a clear histaminergic pattern, obtain C4, C1-inhibitor antigen concentration, and C1-inhibitor functional activity. C1 inhibitor regulates both the classical complement pathway and bradykinin generation through kallikrein and activated factor XII; deficiency permits bradykinin accumulation and increased vascular permeability. PubMed+2PubMedComplements and Their Role in Systemic DisordersPubMedModern Complement Analysis - PMCScienceDirectNovel Therapies for Angiotensin-Converting Enzyme Inhibitor–Induced Angioedema: A Systematic Review of Current Evidence

C1-inhibitor antigen and function must both be measured. In type 1 hereditary angioedema, C1-inhibitor quantity and/or function is reduced; in type 2 disease, approximately 15% of patients have normal or elevated antigen concentration despite reduced functional activity. C4 is usually low even between attacks, whereas C3 is usually normal. PubMedPubMedModern Complement Analysis - PMC

Acquired anti–C1-inhibitor antibodies can produce acquired angioedema with a clinical presentation similar to hereditary C1-inhibitor deficiency; anti–C1-inhibitor antibodies are also reported in systemic lupus erythematosus with angioedema. When onset and context suggest acquired disease, test for anti–C1-inhibitor antibodies and evaluate for an associated condition. PubMed+1PubMedComplements and Their Role in Systemic DisordersScienceDirectDiagnosis, Course, and Management of Angioedema in Patients With Acquired C1-Inhibitor Deficiency

Treat upper-airway attacks as emergencies because laryngeal edema can be life-threatening. Specific acute therapies described for C1-inhibitor–deficient hereditary angioedema include plasma-derived C1-inhibitor, recombinant C1 inhibitor, icatibant 30 mg subcutaneously, and ecallantide 30 mg subcutaneously; acute laryngeal-attack studies report median onset of symptom relief from 15 minutes to approximately 2 hours across regimens. Wiley+2WileyHereditary Angioedema and Gastrointestinal Complications: An Extensive Review of the Literature - Patel - 2015 - Case Reports in Immunology - Wiley Online LibraryScienceDirectEfficacy of Different Medical Therapies for the Treatment of Acute Laryngeal Attacks of Hereditary Angioedema due to C1-esterase Inhibitor Deficiency - ScienceDirectScienceDirectDiagnosis, Course, and Management of Angioedema in Patients With Acquired C1-Inhibitor Deficiency

Patients receiving complement inhibitors have increased susceptibility to serious, life-threatening, or fatal infection with encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. Meningococcal infections have occurred with terminal complement inhibitors and may progress rapidly. asn-online+2asn-online[PDF] Kidney News - December 2025 - American Society of Nephrologypublications aapEculizumab | Drug Lookup | Pediatric Care Online - AAP Publicationspublications aapRavulizumab | Drug Lookup | Pediatric Care Online - AAP Publications

Before initiating a complement inhibitor when feasible, complete or update vaccination against encapsulated bacteria at least 2 weeks before treatment according to current ACIP recommendations; revaccinate according to ACIP schedules during ongoing therapy. Do not initiate iptacopan in a patient with an unresolved serious encapsulated-bacterial infection. asn-onlineasn-online[PDF] Kidney News - December 2025 - American Society of Nephrology

If urgent complement-inhibitor therapy cannot await vaccination, vaccinate as soon as possible and weigh antibacterial prophylaxis individually. The optimal duration, regimen, and effectiveness of antibacterial prophylaxis in vaccinated or unvaccinated recipients of complement inhibitors remain uncertain. asn-onlineasn-online[PDF] Kidney News - December 2025 - American Society of Nephrology

After an abnormal CH50 or AH50 result, use immunochemical assays to measure implicated components; individual complement proteins can be quantified by nephelometry, ELISA, immunoprecipitation methods, or Western blotting. When an immunochemical defect is verified after pathway testing, further functional assays for individual components may not be required. PubMedPubMedModern Complement Analysis - PMC

Distinguish complete from partial deficiency because lower functional activity tracks with infection phenotype in studied C2 and C8 deficiencies. In one cohort, patients with complete complement deficiency and infections consistently had CH50 or AH50 below the lower limit of normal, while partial deficiencies showed higher values and variable infection phenotypes. PubMedPubMedFunctional Complement Analysis Can Predict Genetic Testing Results and Long-Term Outcome in Patients With Complement Deficiencies - PMC

For confirmed hereditary abnormalities, document the affected pathway and infection history and coordinate immunology follow-up for family assessment and management planning. For recurrent angioedema, ensure a written acute-attack plan, access to on-demand therapy, and reassessment of preventive treatment when attacks recur or create procedural risk. ScienceDirect+1ScienceDirectDiagnosis, Course, and Management of Angioedema in Patients With Acquired C1-Inhibitor DeficiencyScienceDirectNovel Therapies for Angiotensin-Converting Enzyme Inhibitor–Induced Angioedema: A Systematic Review of Current Evidence