The human complement system is composed of at least 19 distinct serum proteins, when activated, generate a number of biologically active substances those can contribute in host defense mechanism and also play as mediators of inflammatory reaction. This complement system consist of four functional divisions, the classic and alternate pathways, a single amplification loop that is recruited by each activating pathway and a terminal common pathway of which the activating and amplification sequences are directed.
Activation of the classic pathway occurs by immune complex usually composed of immunoglobulin(Ig) G or M, involves activation of Clq with subsequent cleavage of C4 and C2 to form C42, the classic C3 convertase. Activation of the alternate pathway occurs by immune complex usually composed of IgA or IgE, or with certain microbial polysaccharide, which interact with Factor D, Factor B and C3 to achieve initial C3 activating pathway. In the amplification loop activation, C3b generated by either pathway, interact further with Factor D and Factor B to form the amplification CO) convertase, Cb3B. This C3bB complex in amplification loop is labile because of irreversible decay by regulatory proteins, but in the presence of properdin which can bind to C3b then stablize the convertase forming C3bBP and increase its half-life, thereby profoundly augment the amplification of C3 cleavage and to some extent protect against regulatory proteins, C3bINA and ~IH globulin.
This complement system has been implicated principally in the pathogenesis of bullous pemphigoid, a subepidermal blistering skin disease characterized immunologically by the presence of autoantibody to the skin basement membrane zone. Many research workers demonstrated the deposition of classic pathway components (Clq and C4) and amplification loop components (Factor B and properdin) along the basement membrane zone in addition to IgG and C3 in the lesional skin of the patients with bullous pemphigoid. It has been believed that the deposition of Factor B and properdin occurs via the amplification C3 convertase following generation of C3b by the classic pathway activation.
To demonstrate the biologic role of properdin on the amplification C3 convertase, author examined the amounts of C3 deposit along the basement membrane zone by bullous pemphigoid antibody using two different complement sources, normal human serum and normal human serum devoid of properdin prepared according to Todd´s procedure, by in vitro complement immunofluorescence method.
In this study four patients with bullous pemphigoid, diagnosed histopathologically and immunopathologically, were selected. All these patients had anti-basement membrane zone antibody titers of 1:160 or greater, and demonstrated heavy deposit of C3 along the basement membrane zone by direct immunofluorescence test.
The intensities of C3 deposition when using each different eoi-nplement source -Vvere recongized according to the following criteria:
+ weak linear or discontinuous weak linear fluorescence
+ + easily recognizable, apparent fluorescence
+++ strong band-like or lumpy fluorescence
Control studies were also accomplished in every case and the results were as follows:
1) All four serum samples yielded positive C3 fluorescence reactions of +++ in intensity when normal human serum were used as complement source. When the serum devoid of properdin was substituted as the complement source, the intensities of C3 fluorescence were diminished to + in all cases.
2) All negative control studies showed negative fluorescence reactions and positive control studies showed positive fluorescence reactions in every time of the experiment. This in vitro study confirmed others´ experimental studies on the biologic role of
properdin as the stabilizer of C3 convertase in the amplification loop.
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