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The complement system provides an important effector arm for
many of the innate immune system functions, including host defense,
regulation of acquired immunity, and clearance of immune complexes
and other potentially dangerous material.
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Complement consists of an interacting network of many different
individual proteins that are present in the circulation, in most
body fluids, and on many cell surfaces. Like the coagulation system,
the complement system is a tightly controlled enzyme cascade in
which proenzyme components are activated and a cleavage sequence
is initiated by which biologically active protein fragments are
produced. Figure 189-1 shows the basic schematic
of the complement activation pathways. Although each pathway is activated
differently, they merge at the C3 step and have a common end point
of promoting inflammation, eliminating pathogens, and enhancing
the immune response. When any one of the complement proteins is
missing, including the control proteins and cell-associated receptors, the
resulting dysfunctional system generally leads to disease.1,2 Patients
with complement component deficiencies often present with pyogenic
infections, particularly of encapsulated bacteria including Streptococcus
pneumoniae and Haemophilus influenza type
B or with autoimmune disorders as discussed for each pathway below.
Outright genetic deficiencies are relatively rare, with an estimated
prevalence of 0.03% in the general population, except for deficiency
of the mannan-binding lectin (MBL), which may be present in the
homozygous form in as many as 3–10% of the population.
Subtle changes in the gene sequence that lead to enhanced or decreased
function have been described for several complement proteins.
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Complement abnormalities may underlie disorders, including angioedema,
vasculitis, recurrent bacterial infections, impaired or improper immune
responses, certain renal conditions, and increased incidence of
autoimmune disease. A family history of these symptoms should increase
suspicion of a potential complement deficiency. Specific complement
deficiency associations with particular disease processes are discussed
below.
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Identifying a patient with low complement and distinguishing
between an inherited or acquired deficiency can be challenging.
However, understanding the reason(s) for low or absent complement
guides treatment decisions, including when to use antibiotics, immunizations,
or protein replacement, as well as whether genetic counseling for
inherited deficiencies is needed.
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Evaluation of the complement system is best accomplished using
functional screening tests that are designed to evaluate the integrity
of each pathway.2,3 The classical pathway is evaluated using
the CH50 laboratory test. This test was initially
developed as a hemolytic assay based on complement dependent reactions
with a surface antigen on sheep red blood cells that led to cell lysis.
Because cell lysis required the sequential action of all 9 components
of the classical (C1, C4, and C2) and the terminal pathway (C3,
C4, C6, C7, C9). The CH50 represents the reciprocal of the serum
dilution ...