TY  - CHAP
M1  - Book, Section
TI  - Deficiency of Components of the Complement System
A1  - Cardet, Juan C.
A1  - Wesemann, Duane R.
A2  - Murray, Michael F.
A2  - Babyatsky, Mark W.
A2  - Giovanni, Monica A.
A2  - Alkuraya, Fowzan S.
A2  - Stewart, Douglas R.
PY  - 2014
T2  - Clinical Genomics: Practical Applications in Adult Patient Care
AB  - Disease  summary:Complement  deficiencies  are  rare,  and  typically  result  in  one  or  more  of  the  following  phenotypes:  increased  susceptibility  to  encapsulated  bacteria  (Streptococcus  pneumoniae,  Haemophilus  influenzae,  Neisseria  meningitidis),  and  autoimmunity  (systemic  lupus  erythematosus  [SLE],  atypical  hemolytic  uremic  syndrome  [HUS],  and  membranoproliferative  glomerulonephritis  [GN]).This  chapter  does  not  address  a  single  disease  and  its  implicated  genes,  but  rather  a  subdivision  of  the  immune  system.  Deficiencies  of  the  complement  system  (Table  80-1)  will  be  discussed  in  clusters  of  similar  phenotypic  presentation.  Given  that  the  genetic  basis  for  individual  deficiencies  of  the  complement  components  is  sundry  (and  seldom  clinically  relevant),  individual  genes  will  be  commented  on  only  when  germane  to  clinical  management.Overview  of  the  complement  system:Complement  is  a  system  composed  of  serum  glycoproteins  that  coordinate  cascades  of  events  leading  to  clearance  of  foreign  antigens  and  host-derived  debris  such  as  apoptotic  cells.  Complement  is  involved  in  recognition  of  micro-organisms,  direct  killing  of  micro-organisms,  processing  and  clearance  of  immune  complexes,  as  well  as  regulation  of  lymphocytes.Three  pathways  of  antigen  recognition  and  activation  converge  in  a  common  final  pathway  designed  to  permeabilize  micro-organism  invaders  by  way  of  a  protein  C5  to  C9  protein  complex  that  forms  a  pore  in  microbial  lipid  membranes.  The  pathways  of  activation  are  the  classical,  alternative,  and  mannose-binding  lectin  pathways  (MBL).  C1,  C4,  and  C2  are  early  classical  complement  components.  Factors  D,  B,  are  components  of  the  alternative  pathway.  C3  and  C5  to  C9  are  shared  components.  Complement  regulatory  proteins  include  factor  I,  factor  H,  C4-binding  protein,  and  properdin.  The  proteins  CD59  and  DAF  are  also  regulatory  proteins  whose  deficiency  is  associated  with  paroxysmal  nocturnal  hematuria  and  are  not  described  here.  The  C1  inhibitor  protein  (C1-INH)  deficiency  is  associated  with  hereditary  angioedema  and  is  described  in  Chap.  79.  There  are  multiple  causes  for  secondary  deficiencies  of  C3,  for  example,  deficiency  of  factors  H  and  I.  Deficiency  of  some  complement  receptors  are  also  implicated  in  leukocyte  adhesion  deficiency  (LAD)  and  will  not  be  discussed  in  this  chapter.Inheritance:Almost  all  complement  components  are  inherited  in  an  autosomal  recessive  fashion,  except  for  properdin  deficiency,  which  is  X-linked  recessive,  and  C1  esterase  inhibitor  deficiency,  which  is  autosomal  dominant.  Heterozygously  deficient  individuals  of  components  inherited  in  autosomal  recessive  fashion  are  typically  asymptomatic.Differential  diagnosis:The  differential  diagnosis  for  adult-onset  immune  deficiency  includes  anatomic  derangement  (ie,  fistula,  cerebrospinal  fluid  [CSF]  leak  etc),  common  variable  immune  deficiency,  specific  antibody  deficiency,  antibody  subclass  deficiencies,  congenital  phagocyte  dysfunctions,  medication  or  toxin  effects,  hematologic  cancers  such  as  multiple  myeloma  or  chronic  lymphocytic  leukemia,  and  HIV  or  AIDS.Incidence:Complement  deficiencies  account  for  less  than  1%  of  primary  immunodeficiency  states.  Among  C1  to  C9  components,  C2  deficiency  is  the  most  common  in  Western  countries.  Studies  estimate  5/100,000  is  completely  deficient  in  C2.4  C9  deficiency  is  the  most  common  in  Japan.  There  are  dozens  of  case  reports  of  deficiencies  in  C1q,  and  C3.  C4  protein  is  encoded  in  two  genes,  C4A  and  C4B,  and  a  null  mutation  in  at  least  one  of  the  four  gene  products  can  be  as  high  as  35%  of  the  population.Screening  of  41,083  military  recruits  showed  that  14  individuals  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102702563
ER  -