TY  - CHAP
M1  - Book, Section
TI  - Genetically Determined Disorders of the Complement System
A1  - Sullivan, Kathleen E.
A1  - Winkelstein, Jerry A.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
Y1  - 2019
N1  - 10.1036/ommbid.219
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - The  complement  system  is  composed  of  a  series  of  plasma  proteins  and  cellular  receptors  that,  when  functioning  in  an  ordered  and  integrated  fashion,  serve  as  important  mediators  of  host  defense  and  inflammation.  In  order  for  the  individual  components  of  complement  to  subserve  their  biologic  functions,  however,  they  must  first  be  activated.  Activation  of  the  complement  system  can  occur  via  the  classical  pathway,  the  alternative  pathway,  or  the  lectin  pathway.  Once  activated,  individual  components  act  as  opsonins,  possess  chemotactic  activity,  are  potent  anaphylatoxins,  and  can  assemble  into  the  membrane  attack  complex  and  generate  cytolytic  activity.  In  addition,  the  complement  system  is  important  in  the  processing  of  immune  complexes  and  the  generation  of  a  normal  antibody  response.Some  of  the  complement  genes  have  been  grouped  into  supergene  families  based  on  similarities  in  structure,  function,  and  chromosomal  location.  For  example,  the  genes  encoding  C2,  factor  B,  and  C4  constitute  the  class  III  genes  of  the  major  histocompatibility  complex  on  chromosome  6;  the  products  of  these  genes  are  constituents  of  the  enzymes  that  activate  C3  and  C5.  The  genes  for  C4-binding  protein,  factor  H,  decay-accelerating  factor,  membrane  cofactor  protein,  and  two  of  the  receptors  for  C3  cleavage  products  make  up  another  family  of  complement  genes  located  on  the  long  arm  of  chromosome  l;  the  products  of  these  genes  share  their  ability  to  interact  with  the  activation  products  of  C4  and  C3.  The  synthesis  of  a  number  of  components  of  complement  is  regulated  by  cytokines  such  as  interleukin  1  (IL-1),  tumor  necrosis  factor  (TNF),  IL-6,  and  γ-interferon  and  by  endotoxic  lipopolysaccharide.Genetically  determined  deficiencies  have  been  described  for  most  of  the  individual  components  of  complement.  The  usual  mode  of  inheritance  is  autosomal  recessive  with  only  two  exceptions;  C1-inhibitor  deficiency  is  inherited  as  an  autosomal  dominant  disorder,  and  properdin  deficiency  is  inherited  as  an  X-linked  recessive  disorder.  The  clinical  manifestations  of  individuals  with  complement  deficiencies  have  varied.  Most  individuals  have  had  either  an  increased  susceptibility  to  infection,  rheumatic  disorders,  or  angioedema.  Patients  with  a  deficiency  of  C3  or  with  a  deficiency  of  a  component  in  the  pathways  necessary  for  the  activation  of  C3  have  an  increased  susceptibility  to  infection  with  encapsulated  bacteria,  for  which  C3b-dependent  opsonization  is  an  important  host  defense.  Patients  with  deficiencies  of  terminal  components,  C5  through  C9,  are  markedly  susceptible  to  systemic  neisserial  infections  because  serum  bactericidal  activity  is  an  important  host  defense  against  these  organisms.  The  prevalence  of  rheumatic  disorders,  such  as  systemic  lupus  erythematosus,  vasculitis,  and  membranoproliferative  glomerulonephritis,  is  highest  in  patients  who  are  deficient  in  components  of  the  classical  activating  pathway  (C1,  C4,  and  C2)  and  C3.  Finally,  patients  with  C1-inhibitor  deficiency  present  with  angioedema.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
M3  - doi: 10.1036/ommbid.219
Y2  - 2024/04/19
UR  - ommbid.mhmedical.com/content.aspx?aid=1181458225
ER  -