Inherited Complement Deficiencies

Question 1

Deficient C3b

Answer 1

More susceptible to bacterial infection

Question 2

Deficient C5-C9

Answer 2

No formation of MAC

Susceptible to neisseria

Question 3

Deficient in C1, C2, and C4

Answer 3

Results in immune complex disease because small immune complexes can no longer be opsonized by activation of the classical complement cascade.

Question 4

C3 Deficiency

Answer 4

Inability to activate to complement cascade

Question 5

Factor D deficiency

Answer 5

Critical for alternative pathway

Patients susceptible to neisseria and other encapsulated bacteria.

Question 6

Factor I Deficiency

Answer 6

Reduced cleavage of C3b and C4b causes high C3 convertase formation, resulting in depletion of C3, and therefore C3b

Question 7

MBL Deficiency

Answer 7

Recall this initiates the lectin pathway. The acute phase response is impaired, and the patient has increased susceptibility to severe bacterial infections.

Question 8

C1 Inhibitor Deficiency

Answer 8

Normally, this inhibitor binds to activated C1r and C1s to stop classical pathway and to prevent spontaneous activation of it. The patient loses this control in this disease. They develop HANE and need C1INH replacement therapy.

Question 9

Paroxymal Nocturnal Hemoglobinuria

Answer 9

Results from a genetic deficiency of glycophosphotidylinositol, which is required for surface expression of CD59 and DAF, both of which interfere with MAC formation. MAC formation keeps on a-formin.

Patients will have hemolytic anemia, red urine, and thrombosis.