**6. Complement disorders**

Complement disorders have been traditionally linked to immunodeficiency and associated with severe or frequent infections. More recently, complement has been recognized for its role in inflammation, autoimmune disorders, and vision loss [19]. The identification of hereditary and acquired complement deficiencies in humans has led to a better understanding of the bio‐ logic importance of the complement system in immunity and autoimmune disease (**Table 2**).



C1‐INH‐HAE = hereditary angioedema with C1 inhibitor deficiency; CD59 = cluster of differentiation 59; MAC‐ inhibitory protein (MAC‐IP), membrane inhibitor of reactive lysis (MIRL) or protectin; DAF = complement decay‐ accelerating factor; MASP2 = manna‐binding lectin serine protease 2 (also called mannan‐binding protein‐associated serine protease 2); MBL = mannose‐binding lectin (also called mannose‐binding protein or mannan‐binding protein (MBP); MPGN = membranoproliferative glomerulonephropathy; SLE = systemic lupus erythematous.

**Table 2.** Clinical significance of complement deficiencies [20–24].

MAC insertion into the cytoplasmic membrane causes an intercellular‐extracellular commu‐ nication pore with consequent ion exchange leading to cell death. The sequential steps are as

**1.** As already mentioned, the final stage of the three activation pathways is common and consists in the formation of the "C5 convertase" that breaks the C5 fraction and triggers the appear‐ ance of the "membrane attack complex" (MAC). The steps at every pathway are as follows:

**a.** The "classical pathway": the C4b2aC3b complex catalyzes the cleavage of C5 into C5a

**b.** The "lectin pathway": the C4b2aC3b complex catalyzes the cleavage of C5 into C5a

**c.** The "alternative pathway": a covalent attachment of a "new" C3b that forms part of the

**4.** C5bC6 binds to C7, forming C5bC6‐7 complex, which has already hydrophobic regions

**5.** C5bC6‐7 binds to C8, forming C5bC6‐7‐8 complex, which is capable of forming a 10 Armstrong pore capable of destroying erythrocytes but not able to destroy nucleated cells.

**6.** C5bC6‐7‐8 binds to about 14 C9 units to form the C5b‐C6‐7‐8‐poli9 complex (or MAC), which is capable of forming a 70–100 Armstrong pore by contacting the intracellular with the extracellular medium with the subsequent ion and water exchange, leading to cell

Complement disorders have been traditionally linked to immunodeficiency and associated with severe or frequent infections. More recently, complement has been recognized for its role in inflammation, autoimmune disorders, and vision loss [19]. The identification of hereditary and acquired complement deficiencies in humans has led to a better understanding of the bio‐ logic importance of the complement system in immunity and autoimmune disease (**Table 2**).

**Complement protein Gene (chromosome) Effects of deficiency (commonly associated infections)**

bacteria)

C1r 12p13.31 Meningitis, pneumonia, sepsis (encapsulated

Meningitis, pneumonia, sepsis (*Streptococcus* 

*pneumoniae*, *Neisseria meningitidis*)

C1q 1p36.12 (A, B, and C chains) Immune‐complex disease

that are capable of penetrating into the inner section of the lipid bilayer.

"C3 convertase," forming the C3bBb3b complex. **2.** C5b binds to the cytoplasmic membrane hydrophilic region.

**3.** C5b binds to C6, forming the C5bC6 complex.

follows:

and C5b.

162 A Comprehensive Review of Urticaria and Angioedema

and C5b.

death.

**6. Complement disorders**
