Selective immunoglobulin A deficiency

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"SIgAD" redirects here. For the signals intelligence activity, see SIGAD.
Selective immunoglobulin A deficiency
Immunglobulin A as Dimer.png
The dimeric IgA molecule. 1 H-chain, 2 L-chain, 3 J-chain, 4 secretory component
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, 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.

Signs and symptoms[edit]

‘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]

Although it has some similarities to common variable immunodeficiency (CVID), it does not present the same lymphocyte subpopulation abnormalities.[4] It may anyway progress to CVID.[5]

Those patients with selective immunoglobulin A deficiency may be prone to recurrent infections when on hemodialysis.[6]

Diagnosis[edit]

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).

Cause[edit]

Selective IgA deficiency is inherited and has been associated with differences in chromosomes 18, 14 and 6. The afflicted person usually has no other family members with the disorder.

Pathophysiology[edit]

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[7][8] 6p21
IGAD2 609529 TNFRSF13B 17p11

Treatment[edit]

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[edit]

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.[9][10] 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.[10] The use of IVIG to treat SIGAD without first demonstrating an impairment of specific antibody formation is extremely controversial.[10][11][12]

Prognosis[edit]

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.[13]

As opposed to the related condition CVID, selective IgA deficiency is not associated with an increased risk of cancer.[14]

Epidemiology[edit]

Prevalence varies by population, but is on the order of 1 in 100 to 1 in 1000 people,[15] 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.[16] It is also significantly more common in those with type 1 diabetes.

It is more common in males than in females.[17]

See also[edit]

References[edit]

  1. ^ 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 1905641Freely accessible. PMID 10792368. 
  2. ^ a b c Yel, L. (2010) 'Selective IgA Deficiency', Journal of Clinical Immunology, 30(1), pp. 10-16.
  3. ^ 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. 
  4. ^ 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 1810464Freely accessible. PMID 17223965. 
  5. ^ Harrison's Principles of Internal Medicine, 18th edition, pag. 2704
  6. ^ 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. 
  7. ^ 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 1855370Freely accessible. PMID 17409188. 
  8. ^ Online Mendelian Inheritance in Man (OMIM) 137100
  9. ^ 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 
  10. ^ 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. 
  11. ^ 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 1905641Freely accessible. PMID 10792368. 
  12. ^ 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. 
  13. ^ 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. 
  14. ^ 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 1906562Freely accessible. PMID 12452841. 
  15. ^ "IgA Deficiency: Immunodeficiency Disorders: Merck Manual Professional". Retrieved 2008-03-01. 
  16. ^ 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. 
  17. ^ 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.