"SIgAD" redirects here. For the signals intelligence activity, see SIGAD.
| Selective immunoglobulin A deficiency |
|
| The dimeric IgA molecule. 1 H-chain, 2 L-chain, 3 J-chain, 4 secretory component |
| Specialty |
Immunology |
Selective immunoglobulin A (IgA) deficiency (SIgAD[1]) is a genetic immunodeficiency, a type of hypogammaglobulinemia. 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, in persons older than 4 years. It is the most common of the primary antibody deficiencies. Most such persons remain healthy throughout their lives and are never diagnosed.
Contents
- 1 Signs and symptoms
- 2 Cause
- 3 Pathophysiology
- 4 Diagnosis
- 5 Treatment
- 5.1 Use of IVIG as treatment
- 6 Prognosis
- 7 Epidemiology
- 8 See also
- 9 References
- 10 External links
Signs and symptoms
85–90% of IgA-deficient individuals are asymptomatic, although the reason for lack of symptoms is relatively unknown and continues to be a topic of interest and controversy.[2] Some patients with IgA deficiency have a tendency to develop recurrent sinopulmonary infections, gastrointestinal infections and disorders, allergies, autoimmune conditions, and malignancies.[2] 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. 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.[3]
IgA deficiency and common variable immunodeficiency (CVID) feature similar B cell differentiation arrests,[4] it does not present the same lymphocyte subpopulation abnormalities.[5] IgA-deficient patients may progress to panhypogammaglobulinemia characteristic of CVID.[4] Selective IgA and CVID are found in the same family.[4]
Cause
Selective IgA deficiency is inherited and has been associated with differences in chromosomes 18, 14 and 6. Selective IgA deficiency is often inherited, but has been associated with some congenital intrauterine infections.[4]
Pathophysiology
Pathogenesis of IgA Deficiency
‘In IgA-deficient patients, the common finding is a maturation defect in B cells to produce IgA’. ‘In IgA deficiency, B cells express IgA; however, they are of immature phenotype with the coexpression of IgM and IgD, and they cannot fully develop into IgA-secreting plasma cells’.[2] 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[6][7] |
6p21 |
| IGAD2 |
609529 |
TNFRSF13B |
17p11 |
Diagnosis
When suspected, the diagnosis can be confirmed by laboratory measurement of IgA level in the blood. SigAD is an IgA level < 7 mg/dL with normal IgG and IgM levels (reference range 70–400 mg/dl for adults; children somewhat less).
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.[8][9] 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.[9] The use of IVIG to treat SIGAD without first demonstrating an impairment of specific antibody formation is extremely controversial.[9][10][11]
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.[12]
As opposed to the related condition CVID, selective IgA deficiency is not associated with an increased risk of cancer.[13]
Patients with Selective IgA deficiency are at risk of anaphylaxis from blood transfusions.[4] These patients should receive IgA free containing blood products and ideally blood from IgA-deficient donors.[4]
Epidemiology
Prevalence varies by population, but is on the order of 1 in 100 to 1 in 1000 people,[14] making it relatively common for a genetic disease. SigAD 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.[15] It is also significantly more common in those with type 1 diabetes.
It is more common in males than in females.[16]
See also
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.
- ^ a b c Yel, L. (2010) 'Selective IgA Deficiency', Journal of Clinical Immunology, 30(1), pp. 10-16.
- ^ 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.
- ^ a b c d e f Harrison's Principles of Internal Medicine, 17th edition, pag. 2058
- ^ 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.
- ^ 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
- ^ 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: S1–S63. doi:10.1016/s1081-1206(10)61142-8. Retrieved 27 August 2012.
- ^ 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.
- ^ 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. PMC 120015 .
- ^ 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.
- ^ "IgA Deficiency: Immunodeficiency Disorders: Merck Manual Professional". Retrieved 2008-03-01.
- ^ 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.
- ^ 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.
External links
| Classification |
D
- ICD-10: D80.2
- ICD-9-CM: 279.01
- OMIM: 137100
- MeSH: D017098
- DiseasesDB: 29569
|
| External resources |
- MedlinePlus: 001476
- eMedicine: med/1159
|
|
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
|
|
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
|
