What is the treatment for C2 (complement component 2) deficiency?

Treatment of C2 Deficiency

Patients with C2 deficiency require comprehensive vaccination against encapsulated organisms—particularly meningococcal, pneumococcal, and Haemophilus influenzae type b vaccines—along with consideration of antibiotic prophylaxis for those with recurrent infections, and management of any associated autoimmune manifestations according to standard protocols. 1

Vaccination Strategy (Primary Intervention)

Meningococcal Vaccination

• Administer a 2-dose primary series of MenACWY (meningococcal conjugate vaccine, quadrivalent) 8-12 weeks apart for patients aged 9 months through 55 years with C2 deficiency. 1
• For infants aged 2-18 months, give a 4-dose series of HibMenCY at 2,4,6, and 12-15 months. 1
• For patients aged 9-23 months receiving MCV4, administer doses 3 months apart; for those ≥2 years, space doses 2 months apart. 1
• Revaccinate every 5 years if ongoing risk persists; children receiving the primary series before age 7 should receive the first booster in 3 years, then every 5 years thereafter. 1

Pneumococcal Vaccination

• Children aged 2-5 years should receive 1 dose of PCV13 if they completed 3 doses of PCV before age 24 months, or 2 doses of PCV13 (8 weeks apart) if they received ≤2 doses previously. 1
• Patients aged 6-18 years with C2 deficiency who have not received PCV13 should receive a single dose. 1
• Adults ≥19 years who are PCV13-naive should receive a single dose of PCV13; if they previously received PPSV23, administer PCV13 ≥1 year after the last PPSV23 dose. 1
• Administer PPSV23 ≥8 weeks after PCV13 for all patients ≥2 years, with a second dose of PPSV23 given 5 years later. 1

Critical Vaccination Timing

• When using MCV4-D (Menactra), administer it ≥4 weeks after completion of all PCV doses, as simultaneous administration reduces antibody response to some pneumococcal serotypes. 1
• Do not delay vaccination while awaiting complete diagnostic workup, as patients face immediate risk for life-threatening infections. 2

Antibiotic Prophylaxis

• Consider lifelong penicillin prophylaxis for patients with recurrent bacterial infections, particularly those with documented gonococcal or meningococcal disease. 3
• Daily prophylactic antibiotics should be considered for C2-deficient patients despite vaccination, given the extreme infection risk from encapsulated organisms. 2
• Aggressive therapeutic and prophylactic antibiotic therapy are indicated for recurrent sinopulmonary infections. 1

Management of Associated Autoimmune Disease

• Manage lupus-like manifestations according to standard rheumatologic guidelines with immunosuppression; C2 deficiency does not preclude the use of corticosteroids or disease-modifying agents. 2
• C2 deficiency is strongly associated with systemic lupus erythematosus in adults, requiring vigilant monitoring and standard SLE treatment protocols. 4

Experimental and Future Therapies

• Recombinant human C2 (rhC2) has demonstrated restoration of classical complement pathway activity in vitro and may serve as potential protein replacement therapy, though this remains investigational. 4
• Fresh frozen plasma infusions have demonstrated therapeutic effects in C2-deficient patients with associated disease, though protein replacement therapy has not been formally evaluated in clinical trials. 4

Routine Monitoring and Follow-Up

• All routine vaccines based on the CDC annual schedule should be administered; none are contraindicated in C2 deficiency. 1
• Consult immunology or complement specialists for all confirmed C2 deficiencies to ensure comprehensive evaluation, appropriate genetic testing, and optimal long-term management. 5, 2
• Monitor for development of autoimmune manifestations, particularly SLE-like disease, which occurs more commonly in adults with C2 deficiency. 5, 2

Common Pitfalls to Avoid

• Do not assume normal C3 and C4 levels exclude complement deficiency, as C2 deficiency may not lower these screening tests. 2
• Recognize that C2 deficiency presents with both increased infection susceptibility (particularly in children) and autoimmune disease (particularly in adults), requiring dual vigilance. 4, 3
• Blood specimens for complement testing must be placed on ice or refrigerated immediately after drawing to prevent falsely low results from complement component degradation. 5, 2