The CH50 test is a widely available test of classic complement pathway function, based on an antibody-dependent hemolytic assay, which measures the serum dilution that results in lysis of 50% of sheep red blood cells. The CH50 test depends on the function of all nine complement proteins, C1 through C9. The AH50 test, which measures complement activation using red blood cells from different species (e.g., rabbit) that can activate the alternative pathway without antibody, is less widely available than the CH50 test and requires the alternative pathway components and C5 to C9. Abnormal results of both tests indicate a deficiency in a terminal component common to both pathways, whereas an abnormal result of one or the other test indicates a deficiency of an early component of the respective pathway. If the CH50 or AH50 levels are abnormal, individual components can be analyzed in specialized laboratories.
Determination of C1-inhibitor levels and function is needed to diagnose hereditary angioedema. Some functional tests miss rare mutations that allow C1-inhibitor to bind C1s, but not one or more of the other enzymes with which it interacts. Low C1-inhibitor levels or function results in chronically decreased C4 levels and decreased C2 levels during acute attacks. Low C1q levels are found in acquired C1-inhibitor deficiency, which distinguishes it from hereditary angioedema. Tests for autoantibodies to C1-inhibitor and C1q can be performed by enzyme-linked immunosorbent assay.
Specific treatment of complement deficiencies with component replacement is not available. Long, frequent courses of antibiotics constitute the primary therapy. Immunization of patients and close contacts with pneumococcal and meningococcal vaccines may be useful, but infections may still occur in immunized complement-deficient patients. Replacement of complement proteins by plasma transfusion has been used in some patients with C2 deficiency, factor H deficiency, or factor I deficiency. MCP deficiency is treated with renal transplantation because it is a membrane protein.
Patients with C1-inhibitor deficiency and frequent episodes of angioedema respond to prophylactic use of an oral attenuated androgen (stanozolol or danazol), which increases serum concentrations of C1-inhibitor. Adverse effects, including masculinization in females, growth arrest, and hepatitis, limit their use. Prophylactic administration of fresh frozen plasma before surgery can prevent angioedema, but administration during an acute episode may exacerbate the episode. Angioedema of the airway can present as an acute emergency, necessitating a tracheostomy because administration of epinephrine, antihistamines, or corticosteroids is ineffective in reversing this type of angioedema. Purified C1-inhibitor is available and can be used prophylactically (before surgery) and during acute episodes of angioedema. Angiotensin-converting enzyme inhibitors, such as captopril, should be avoided in patients with C1-inhibitor deficiency because these drugs can precipitate episodes of angioedema by inhibiting degradation of kinins that mediate edema formation. Novel therapeutic agents, including a kallikrein inhibitor and a bradykinin receptor 2 antagonist, are being investigated as potential therapy for hereditary angioedema.
Hematopoietic stem cell transplantation (HSCT) can cure some patients with primary immunodeficiency disease (Table 76-1). Use of HSCT is limited to immunodeficiency diseases with T-cell defects, some metabolic storage diseases (see Chapters 55 and 56), malignancies (see Chapter 154), aplastic anemia (see Chapter 150), hemoglobinopathies (Chapter 150), and a few other disorders.