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igadeficiency

IgA deficiency

see also:

introduction

  • IgA deficiency is a subset of humoral (B-cell) immunodeficiencies
  • low or absent serum IgA levels may be an isolated immunoglobulin deficiency such as selective IgA deficiency, or be also associated with deficiency of other immunoglobulins such as IgG and IgM as with common variable immunodeficiency (CVID)
  • IgA is secreted by B cells in submucosal lymphoid tissues, Peyer patches, and tonsils, and is secreted into most body fluids such as intestinal and bronchial secretions, saliva, tears, prostatic fluid, and breast milk
  • secreted IgA binds to, and neutralises certain bacteria and their toxins (eg. Cl. difficile toxins), and helps prevent invasion of these bacteria through the mucosal barriers by promoting phagocytosis of these organisms
  • IgA deficiency by itself is often asymptomatic but may be associated with:
    • recurrent bacterial infections
    • increased rates of allergy and auto-immune disease
    • increased incidence of certain cancers

Dx workup

  • serum immunoglobulins are the primary investigation to perform
    • isolated low or absent IgA strongly indicates SIGAD or SIGAD with IgG subclass deficiency:
      • check IgG sub classes if older than 1 year old as some will have CVID without low total IgG or IgM levels
      • check serum IgG antibodies against gliadin and tissue transglutaminase to screen for coeliac disease
      • patients likely to need blood transfusions should also be assessed for high levels of anti-IgA which would place them at risk for anaphylaxis to blood products
      • cease any drugs which may be causing an acquired form of SIGAD
    • low IgG and IgA levels suggest CVID, SIGAD with IgG subclass deficiency, XLA, AR-Hyper-IgM, ADA deficiency, PNP deficiency, protein-loss enteropathy, intestinal lymphangiectasia, nephrotic syndrome
  • if the above are abnormally low, consider screening for associated auto-immune diseases

selective IgA deficiency (SIGAD)

  • occurs in 1 in 400 to 1 in 18,500 depending upon ethnic population
  • it is a heterogeneous disorder and may be partial or total deficiency
  • it has a similar gene defects as does CVID, selective IgG subclass deficiencies, and the syndrome of recurrent sinopulmonary infections with normal serum immunoglobulin such as:
    • mutation in the tumor necrosis factor receptor family member TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) - TACI facilitate isotype switching in B cells
    • function-loss mutations in several non–major histocompatibility complex (MHC) genes
  • ~20% of patients have a family history of either SIGAD or CVID
  • variable genetics, but may also be acquired from infections or drugs although in these cases tends to be reversible
    • drugs which may cause reversible IgA deficiency include phenytoin, carbamazepine, valproic acid, zonisamide, sulfasalazine, gold compounds, D-penicillamine, hydroxychloroquine, NSAIDs, captopril, and thyroxine
    • cyclosporin A has been reported to cause permanent IgA deficiency
  • these patients have B cells but they have been developmentally arrested and lack the ability to differentiate into IgA-secreting plasma cells may be caused by the deficiency of cytokines, such as interleukins IL-4, IL-6, IL-7, and IL-10
  • usually asymptomatic
  • may cause:
  • as 10-44% have anti-IgA antibodies, rarely, severe allergic reactions to blood transfusions may occur as these contain IgA
  • occurs in ~2% of patients with coeliac disease while celiac disease occurs in 10-30% of these patients
  • the condition may result in failed diagnosis of celiac disease as the high levels of certain IgA antibodies usually seen in celiac disease do not occur
  • may be associated with increased risk of cancers such as:
    • gastric and colonic adenocarcinoma
    • acute lymphoblastic leukemia
    • multiple myeloma
    • malignant thymoma
    • hepatoma
    • ovarian cancer
    • lymphosarcoma
    • squamous cell carcinoma
    • melanoma
  • may be associated with deficiencies in antipneumococcal antibodies
  • IgG2 and IgG4 subclass deficiencies are often found in persons who are more severely affected
  • may progress to CVID

common variable immunodeficiency (CVID)

ataxia-telangiectasia

  • 1 in 100,000 births although 1-2% population have the HZ allele
  • median age of death is 20yrs, oldest was 34 years
  • AR condition with progressive neurologic impairment, cerebellar ataxia, variable immunodeficiency with susceptibility to sinopulmonary infections, impaired organ maturation, x-ray hypersensitivity, ocular and cutaneous telangiectasia
  • 70% have low IgA levels
  • usually have a normal or low level of IgG, and a normal or high level of IgM
  • may have low IgE levels
  • also have elevated serum AFP, CEA and chromosomal 7 and 14 abnormalities

X-linked Bruton agammaglobulinemia (XLA)

  • 1 in 70,000-250,000 births
  • males are affected and usually present in early childhood with recurrent infections
igadeficiency.txt · Last modified: 2019/07/13 17:10 by wh