"SIgAD" redirects here. For the signals intelligence activity, see SIGAD.
| Selective immunoglobulin A deficiency |
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The dimeric IgA molecule. 1 H-chain, 2 L-chain, 3 J-chain, 4 secretory component
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| Classification and external resources |
| Specialty |
hematology |
| ICD-10 |
D80.2 |
| ICD-9-CM |
279.01 |
| OMIM |
137100 |
| DiseasesDB |
29569 |
| MedlinePlus |
001476 |
| eMedicine |
med/1159 |
| MeSH |
D017098 |
Selective immunoglobulin A (IgA) deficiency (SIgAD[1]) is a genetic immunodeficiency. People with this deficiency lack immunoglobulin A (IgA), a type of antibody that protects against infections of the mucous membranes lining the mouth, airways, and digestive tract. It is defined as an undetectable serum IgA level in the presence of normal serum levels of IgG and IgM. It is the most common of the primary antibody deficiencies.
Contents
- 1 Epidemiology
- 2 Pathophysiology
- 3 Symptoms and diagnosis
- 4 Treatment
- 4.1 Use of IVIG as treatment
- 5 Prognosis
- 6 References
Epidemiology
Prevalence varies by population, but is on the order of up to 1 in 333 people,[2] making it relatively common for a genetic disease.
It is more common in males than in females.[3]
Pathophysiology
There is an inherited inability to produce immunoglobulin A (IgA), a part of the body's defenses against infection at the body's surfaces (mainly the surfaces of the respiratory and digestive systems). As a result, bacteria at these locations are somewhat more able to cause disease.
Types include:
| Type |
OMIM |
Gene |
Locus |
| IGAD1 |
137100 |
Unknown; MSH5 suggested[4][5] |
6p21 |
| IGAD2 |
609529 |
TNFRSF13B |
17p11 |
Symptoms and diagnosis
People with selective IgA deficiency are usually asymptomatic,[6][7] but can have increased frequency of infections, particularly in the respiratory, digestive and genitourinary systems, for example, sinusitis and urinary tract infections. These infections are generally mild and would not usually lead to an in-depth workup except when unusually frequent. They may present with severe reactions including anaphylaxis to blood transfusions or intravenous immunoglobulin due to the presence of IgA in these blood products. When suspected, the diagnosis can be confirmed by laboratory measurement of IgA level in the blood. Patients have an increased susceptibility to pneumonia and recurrent episodes of other respiratory infections and a higher risk of developing autoimmune diseases in middle age.[8]
Although it has some similarities to common variable immunodeficiency, it does not present the same lymphocyte subpopulation abnormalities.[9] It may anyway progress to CVID.[10]
Those patients with selective immunoglobulin A deficiency may be prone to recurrent infections when on hemodialysis.[11]
Treatment
The treatment consists of identification of comorbid conditions, preventive measures to reduce the risk of infection, and prompt and effective treatment of infections. Infections in an IgA-deficient person are treated as usual (i.e., with antibiotics). There is no treatment for the underlying disorder.
Use of IVIG as treatment
There is a historical popularity in using intravenous immunoglobulin (IVIG) to treat SIGAD, but the consensus is that there is no evidence that IVIG treats this condition.[12][13] In cases where a patient presents SIGAD and another condition which is treatable with IVIG, then a physician may treat the other condition with IVIG.[13] The use of IVIG to treat SIGAD without first demonstrating an impairment of specific antibody formation is extremely controversial.[7][13][14]
Prognosis
Prognosis is excellent, although there is an association with autoimmune disease. Of note, selective IgA deficiency can complicate the diagnosis of one such condition, celiac disease, as the deficiency masks the high levels of certain IgA antibodies usually seen in celiac disease.[15] Selective IgA deficiency occurs in 1 of 39 to 57 patients with celiac disease. This is much higher than the prevalence of selective IgA deficiency in the general population, which is estimated to be approximately 1 in 400 to 18 500, depending on ethnic background. The prevalence of celiac disease in patients with selective IgA deficiency ranges from 10% to 30%, depending on the evaluated population.[16]
As opposed to the related condition CVID, selective IgA deficiency is not associated with an increased risk of cancer.[17]
References
- ^ Hammarström, L; Vorechovsky, I; Webster, D (May 2000). "Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID)". Clinical and Experimental Immunology 120 (2): 225–231. doi:10.1046/j.1365-2249.2000.01131.x. PMC 1905641. PMID 10792368. Retrieved 17 April 2014.
- ^ "IgA Deficiency: Immunodeficiency Disorders: Merck Manual Professional". Retrieved 2008-03-01.
- ^ Weber-Mzell D, Kotanko P, Hauer AC, et al. (March 2004). "Gender, age and seasonal effects on IgA deficiency: a study of 7293 Caucasians". Eur. J. Clin. Invest. 34 (3): 224–8. doi:10.1111/j.1365-2362.2004.01311.x. PMID 15025682.
- ^ Sekine H, Ferreira RC, Pan-Hammarström Q, et al. (April 2007). "Role for Msh5 in the regulation of Ig class switch recombination". Proc. Natl. Acad. Sci. U.S.A. 104 (17): 7193–8. doi:10.1073/pnas.0700815104. PMC 1855370. PMID 17409188.
- ^ Online 'Mendelian Inheritance in Man' (OMIM) 137100
- ^ Tierney, Lawrence M.; McPhee, Stephen J.; Papadakis, Maxine A. (2008). Current medical diagnosis & treatment, 2008. McGraw-Hill Medical. p. 694. ISBN 0-07-149430-8.
- ^ a b Hammarström, L.; Vorechovsky, I.; Webster, D. (2000). "Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID)". Clinical and experimental immunology 120 (2): 225–231. doi:10.1046/j.1365-2249.2000.01131.x. PMC 1905641. PMID 10792368.
- ^ Koskinen S (1996). "Long-term follow-up of health in blood donors with primary selective IgA deficiency". J Clin Immunol 16 (3): 165–70. doi:10.1007/BF01540915. PMID 8734360.
- ^ Litzman J, Vlková M, Pikulová Z, Stikarovská D, Lokaj J (February 2007). "T and B lymphocyte subpopulations and activation/differentiation markers in patients with selective IgA deficiency". Clin. Exp. Immunol. 147 (2): 249–54. doi:10.1111/j.1365-2249.2006.03274.x. PMC 1810464. PMID 17223965.
- ^ Harrison's Principles of Internal Medicine, 18th edition, pag. 2704
- ^ Kuo MC, Hwang SJ, Chang JM, Tsai JC, Tsai JH, Lai YH (December 1998). "Recurrent infections in haemodialysis patients--do not forget selective immunoglobulin A deficiency". Nephrol. Dial. Transplant. 13 (12): 3220–2. doi:10.1093/ndt/13.12.3220. PMID 9870497.
- ^ American Academy of Allergy, Asthma, and Immunology. "Five Things Physicians and Patients Should Question" (PDF). Choosing Wisely: an initiative of the ABIM Foundation (American Academy of Allergy, Asthma, and Immunology). Retrieved August 14, 2012
- ^ a b c Francisco A. Bonilla; I. Leonard Bernstein; David A. Khan; Zuhair K. Ballas; Javier Chinen; Michael M. Frank; Lisa J. Kobrynski; Arnold I. Levinson; Bruce Mazer (May 2005). "Practice parameter for the diagnosis and management of primary immunodeficiency" (PDF). Annals of Allergy, Asthma & Immunology 94. Retrieved 27 August 2012.
- ^ Mark Ballow (2008). "85". In Robert R. Rich. Clinical immunology : principles and practice (3rd ed.). St. Louis, Mo.: Mosby/Elsevier. pp. 1265–1280. ISBN 978-0323044042.
- ^ Prince, Harry E.; Gary L. Norman; Walter L. Binder (November 2002). "Validation of an In-House Assay for Cytomegalovirus Immunoglobulin G (CMV IgG) Avidity and Relationship of Avidity to CMV IgM Levels". Clin Vaccine Immunol 9 (6): 1295–1300. doi:10.1128/CDLI.9.4.824-827.2002.
- ^ J. Decker Butzner1,a, K. E.; McGowan, KE; Lyon, EM; Butzner, JD (July 2008). "Celiac Disease and IgA Deficiency: Complications of Serological Testing Approaches Encountered in the Clinic". Clinical Chemistry 54 (7): 1203–1209. doi:10.1373/clinchem.2008.103606. PMID 18487281.
- ^ Mellemkjaer L, Hammarstrom L, Andersen V, et al. (2002). "Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study". Clin. Exp. Immunol. 130 (3): 495–500. doi:10.1046/j.1365-2249.2002.02004.x. PMC 1906562. PMID 12452841.
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Immune disorders: Lymphoid and complement immunodeficiency (D80–D85, 279.0–4)
|
|
| Primary |
| Antibody/humoral (B) |
| Hypogammaglobulinemia |
- X-linked agammaglobulinemia
- Transient hypogammaglobulinemia of infancy
|
|
| Dysgammaglobulinemia |
- IgA deficiency
- IgG deficiency
- IgM deficiency
- Hyper IgM syndrome (1
- 2
- 3
- 4
- 5)
- Wiskott-Aldrich syndrome
- Hyper-IgE syndrome
|
|
| Other |
- Common variable immunodeficiency
- ICF syndrome
|
|
|
| T cell deficiency (T) |
- thymic hypoplasia: hypoparathyroid (Di George's syndrome)
- euparathyroid (Nezelof syndrome
- Ataxia telangiectasia)
peripheral: Purine nucleoside phosphorylase deficiency
|
|
| Severe combined (B+T) |
- x-linked: X-SCID
autosomal: Adenosine deaminase deficiency
- Omenn syndrome
- ZAP70 deficiency
- Bare lymphocyte syndrome
|
|
|
| Acquired |
|
|
Leukopenia:
Lymphocytopenia |
- Idiopathic CD4+ lymphocytopenia
|
|
| Complement deficiency |
- C1-inhibitor (Angioedema/Hereditary angioedema)
- Complement 2 deficiency/Complement 4 deficiency
- MBL deficiency
- Properdin deficiency
- Complement 3 deficiency
- Terminal complement pathway deficiency
- Paroxysmal nocturnal hemoglobinuria
- Complement receptor deficiency
|
|
|
Index of the immune system
|
|
| Description |
- Physiology
- cells
- autoantigens
- autoantibodies
- complement
- surface antigens
- IG receptors
|
|
| Disease |
- Allergies
- Immunodeficiency
- Immunoproliferative immunoglobulin disorders
- Hypersensitivity and autoimmune disorders
- Neoplasms and cancer
|
|
| Treatment |
- Procedures
- Drugs
- antihistamines
- immunostimulants
- immunosuppressants
- monoclonal antibodies
|
|
|
|
Cell surface receptor deficiencies
|
|
G protein-coupled receptor
(including hormone) |
| Class A |
- TSHR (Congenital hypothyroidism 1)
- LHCGR (Luteinizing hormone insensitivity, Leydig cell hypoplasia, Male-limited precocious puberty)
- FSHR (Follicle-stimulating hormone insensitivity, XX gonadal dysgenesis)
- GnRHR (Gonadotropin-releasing hormone insensitivity)
- EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2)
- AVPR2 (Nephrogenic diabetes insipidus 1)
- PTGER2 (Aspirin-induced asthma)
|
|
| Class B |
- PTH1R (Jansen's metaphyseal chondrodysplasia)
|
|
| Class C |
- CASR (Familial hypocalciuric hypercalcemia)
|
|
| Class F |
- FZD4 (Familial exudative vitreoretinopathy 1)
|
|
|
Enzyme-linked receptor
(including
growth factor) |
| RTK |
- ROR2 (Robinow syndrome)
- FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome)
- FGFR2 (Apert syndrome, Antley–Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson–Weiss syndrome)
- FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome)
- INSR (Donohue syndrome
- Rabson–Mendenhall syndrome)
- NTRK1 (Congenital insensitivity to pain with anhidrosis)
- KIT (KIT Piebaldism, Gastrointestinal stromal tumor)
|
|
| STPK |
- AMHR2 (Persistent Müllerian duct syndrome II)
- TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia)
- TGFBR1/TGFBR2 (Loeys–Dietz syndrome)
|
|
| GC |
- GUCY2D (Leber's congenital amaurosis 1)
|
|
|
| JAK-STAT |
- Type I cytokine receptor: GH (Laron syndrome)
- CSF2RA (Surfactant metabolism dysfunction 4)
- MPL (Congenital amegakaryocytic thrombocytopenia)
|
|
| TNF receptor |
- TNFRSF1A (TNF receptor associated periodic syndrome)
- TNFRSF13B (Selective immunoglobulin A deficiency 2)
- TNFRSF5 (Hyper-IgM syndrome type 3)
- TNFRSF13C (CVID4)
- TNFRSF13B (CVID2)
- TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A)
|
|
| Lipid receptor |
- LRP: LRP2 (Donnai–Barrow syndrome)
- LRP4 (Cenani–Lenz syndactylism)
- LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1)
- LDLR (LDLR Familial hypercholesterolemia)
|
|
| Other/ungrouped |
- Immunoglobulin superfamily: AGM3, 6
- Integrin: LAD1
- Glanzmann's thrombasthenia
- Junctional epidermolysis bullosa with pyloric atresia
EDAR (EDAR hypohidrotic ectodermal dysplasia)
- PTCH1 (Nevoid basal-cell carcinoma syndrome)
- BMPR1A (BMPR1A juvenile polyposis syndrome)
- IL2RG (X-linked severe combined immunodeficiency)
|
|
- See also
- cell surface receptors
|
Index of cells
|
|
| Description |
- Structure
- Organelles
- peroxisome
- cytoskeleton
- centrosome
- epithelia
- cilia
- mitochondria
- Membranes
- Membrane transport
- ion channels
- vesicular transport
- solute carrier
- ABC transporters
- ATPase
- oxidoreduction-driven
|
|
| Disease |
- Structural
- peroxisome
- cytoskeleton
- cilia
- mitochondria
- nucleus
- scleroprotein
- Membrane
- channelopathy
- solute carrier
- ATPase
- ABC transporters
- other
- extracellular ligands
- cell surface receptors
- intracellular signalling
- Vesicular transport
- Pore-forming toxins
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