Figure 3.
Inborn errors of complement underlying specific infections. Individual patients with deficits of the classical arm of complement may be prone to single types of infection. The penetrance of these defects for each infection is relatively low. In contrast, most, if not all, patients with autosomal recessive deficiencies of most terminal components of complement (C5, C6, C7, C8B, C9) and two activating proteins (properdin and factor D) are selectively prone to invasive disease triggered by Neisseria species (7). Defects of C8A have not been reported to underlie such infections. These defects were characterized at the protein level between 1976 and 1989 (44, 45, 46, 47, 48, 49, 50); their occurrence in patients with Neisseria infection was first described in the same period (44, 45, 47, 49, 50, 51, 52), and the corresponding genotypes were identified between 1993 and 2001 (53, 54, 55, 56, 57, 58, 59, 60). Unlike the Mendelian and monogenic infections analyzed from 1996 onward, these defects were not identified by forward genetics-based searches for genetic etiologies of Neisseria infections. They were found through reverse genetics-like approaches based on analyses of the newly characterized complement system in patients hospitalized for various inflammatory or infectious conditions. Refer to the image caption for details. The chart displays a timeline from 1970 to 2000, detailing the emergence and genetic basis of human monogenic infections related to complement system deficiencies. The y-axis lists genes: C 5, C 6, C 7, C 8 a, C 8 b, C 9, Properdin, and Factor D. The x-axis spans from 1970 to 2000. Key events are marked with icons: blue figures for the first patient, orange bacteria for the first Neisseria infection, and purple D N A strands for the first mutation. The first patients with deficiencies in C 5, C 6, C 7, C 8 b, C 9, Properdin, and Factor D are noted between 1976 and 1989. The first Neisseria infections linked to these deficiencies are recorded around the same period. The first mutation are identified between 1993 and 2001. The chart highlights that deficiencies in C 5, C 6, C 7, C 8 b, C 9, Properdin, and Factor D are selectively prone to invasive Neisseria infections, while C 8 a deficiencies are not associated with such infections.

Inborn errors of complement underlying specific infections. Individual patients with deficits of the classical arm of complement may be prone to single types of infection. The penetrance of these defects for each infection is relatively low. In contrast, most, if not all, patients with autosomal recessive deficiencies of most terminal components of complement (C5, C6, C7, C8B, C9) and two activating proteins (properdin and factor D) are selectively prone to invasive disease triggered by Neisseria species (7). Defects of C8A have not been reported to underlie such infections. These defects were characterized at the protein level between 1976 and 1989 (44, 45, 46, 47, 48, 49, 50); their occurrence in patients with Neisseria infection was first described in the same period (44, 45, 47, 49, 50, 51, 52), and the corresponding genotypes were identified between 1993 and 2001 (53, 54, 55, 56, 57, 58, 59, 60). Unlike the Mendelian and monogenic infections analyzed from 1996 onward, these defects were not identified by forward genetics-based searches for genetic etiologies of Neisseria infections. They were found through reverse genetics-like approaches based on analyses of the newly characterized complement system in patients hospitalized for various inflammatory or infectious conditions.

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