Antibody Deficiency Syndromes (Including Diagnosis and Treatment)

  • Kenneth Paris
  • Lily Leiva
  • Ricardo U. Sorensen
Part of the Allergy Frontiers book series (ALLERGY, volume 5)

Antibody deficiency syndromes range from an absence of all immunoglobulins (agammaglobulinemia) to milder, but clinically relevant, deficiencies of specific antibodies in patients with normal immunoglobulin concentrations. In clinical practice, physicians encounter many forms of antibody deficiencies that do not fit the strict criteria for each syndrome that has been defined by several expert groups in primary immunodeficiencies [1, 2]. We recognize that antibody deficiencies are the most frequently reported immunodeficiencies in different areas of the world [3] and antibody deficiencies are the most frequently encountered immunodeficiencies in clinical immunology practice. The antibody deficiencies with the least clinical impact are found at the highest frequency in the population. For example, IgA deficiency, which can be observed in asymptomatic individuals, is the most frequently encountered immunodeficiency [4] while agammaglobulinemias are relatively rare. There may be a common misconception that the less frequent severe antibody deficiency syndromes are not relevant in clinical practice. However, early diagnosis of an antibody deficiency requires awareness and a thorough evaluation and may prevent permanent sequelae from the severe infections that can occur.


Allergy Clin Immunol Common Variable Immunodeficiency Primary Immunodeficiency Disease Antibody Deficiency Polysaccharide Antigen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Notarangelo L, Casanova J-L, Fischer A, et al. (2004) Primary immunodeficiency diseases: An update. J Allergy Clin Immunol 114: 677–687CrossRefPubMedGoogle Scholar
  2. 2.
    Conley M E, Nortarangelo L D, Etzioni A (1999) Diagnostic criteria for primary immunodeficiencies. Clin Immunol 93: 190–197CrossRefPubMedGoogle Scholar
  3. 3.
    Sorensen R U, Moore C (2000) Antibody deficiency syndromes. Peds Clin NA 47: 1225–1252CrossRefGoogle Scholar
  4. 4.
    Hanson L A, Bjorkander J, Oxelius V, Selective IgA deficiency. 1983: New York, pp. 62–84Google Scholar
  5. 5.
    Ochs H D, Wedgwood R J (1987) IgG subclass deficiencies. Ann Rev Med 38: 325–340CrossRefPubMedGoogle Scholar
  6. 6.
    Cooper M D (1987) Current concepts. B lymphocytes. Normal development and function. N Engl J Med 317: 1452–1456PubMedCrossRefGoogle Scholar
  7. 7.
    Conley M, Rohrer J, Minegishi Y (2000) X-linked agammaglobulinemia. Clin Rev Allergy Immunol 19: 183–204CrossRefPubMedGoogle Scholar
  8. 8.
    Wasserman R L, Sorensen R U (1999) Evaluating children with respiratory tract infections: the role of immunization with bacterial polysaccharide vaccine. Pediatr Infect Dis J 18: 157–163CrossRefPubMedGoogle Scholar
  9. 9.
    Lederman H M, Winkelstein J A (1985) X-linked agammaglobulinemia: an analysis of 96 patients. Medicine 64: 145–156CrossRefPubMedGoogle Scholar
  10. 10.
    Paris K, Sorensen R (2007) Assessment and clinical interpretation of polysaccharide antibody response. Ann Allergy Asthma Immunol 99: 462–464PubMedCrossRefGoogle Scholar
  11. 11.
    Landesman S H, Schiffman G (1981) Assessment of the antibody response to pneumococcal vacine in high risk population. Rev Infect Dis 3: S184–S197PubMedGoogle Scholar
  12. 12.
    Lawrence E M, Edwards K M, Schiffmann G, Thompson J M, Vaughn W K, Wright P F (1983) Pneumococcal vaccine in normal children. Primary and secondary vaccination. Am J Dis Child 137: 846–850PubMedGoogle Scholar
  13. 13.
    Ochs H, Buckley R H, Kobayashi R H, et al. (1992) Antibody responses to Bacteriophage oX174 in patients with adenosine deaminase deficiency. Blood 80: 1163–1171PubMedGoogle Scholar
  14. 14.
    Conley M, Mathias D, Treadaway J, Minegishi Y, Rohrer J M Y, Rohrer J (1998) Mutations in btk in patients with presumed X-linked agammaglobulinemia. Am J Hum Genet 62: 1034–1043CrossRefPubMedGoogle Scholar
  15. 15.
    Holinski-Feder E, Weiss M, Brandau O, et al. (1998) Mutation screening of the BTK gene in 56 families with X-linked agammaglobulinemia (XLA): 47 unique mutations without correlation to clinical course. Pediatrics 101: 276–284CrossRefPubMedGoogle Scholar
  16. 16.
    Wood P, Smith E, Hazelwood M, Joyce H, Granoff D, Kumararatne D (2000) Atypical btk deficiency presenting with selective polysaccharide antibody deficiency in the presence of normal serum immunoglobulin [Abstract]. J Allergy Clin Immunol 105: S219CrossRefGoogle Scholar
  17. 17.
    Kainulainen L, Varpula M, Liippo K, Svedstrom E, Nikoskelainen J, Ruuskanen O (1999) Pulmonary abnormalities in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol 104: 1031–1036CrossRefPubMedGoogle Scholar
  18. 18.
    Polmar SH, Sorensen RU, Immunoglobulin replacement therapy in primary immunodeficiency diseases, in Clinical Immunology: Principles and Practice, R. Rich, Ed. 1995, Mosby: St. Louis, pp. 1865–1875Google Scholar
  19. 19.
    Cunningham-Rundles C, Bodian C (1999) Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol 92: 34–48CrossRefPubMedGoogle Scholar
  20. 20.
    Spickett G (2001) Current perspectives on common variable immunodeficiency (CVID). Clin Exp Allergy 31(4): 536–542CrossRefPubMedGoogle Scholar
  21. 21.
    Espanol T, Catala M, Hernandez M, Caragol I, Bertran J M (1996) Development of a common variable immunodeficiency in IgA-deficient patients. Clin Immunol Immunopathol 80: 333–335CrossRefPubMedGoogle Scholar
  22. 22.
    Hermaszewski, R A, Webster A D (1993) Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications. Q J Med 86: 31–42PubMedGoogle Scholar
  23. 23.
    Cunningham-Rundles C (1989) Clinical and immunologic analyses of 103 patients with common variable immunodeficiency. J Clin Immunol 9: 22–33CrossRefPubMedGoogle Scholar
  24. 24.
    Luzi G, Zullo A, Iebba F, et al. (2003) Duodenal pathology and clinical-immunological implications in common variable immunodeficiency patients. Am J Gastroenterol 98(1): 118–121CrossRefPubMedGoogle Scholar
  25. 25.
    Fasano M B, Sullivan K E, Sarpong S B, et al. (1996) Sarcoidosis and common variable immunodeficiency. Report of 8 cases and review of the literature. Medicine 75: 251–261CrossRefPubMedGoogle Scholar
  26. 26.
    Kinlen L J, Webster A D, Bird A G, et al. (1985) Prospective study of cancer in patients with hypogammaglobulinaemia. Lancet 1: 263–266CrossRefPubMedGoogle Scholar
  27. 27.
    Cunningham-Rundles C, Siegal F P, Cunningham-Rundles S, Lieberman P (1987) Incidence of cancer in 98 patients with common varied immunodeficiency. J Clin Immunol 7: 294–299CrossRefPubMedGoogle Scholar
  28. 28.
    Hammarstrom L, Smith C I E, Genetic approach to common variable immunodeficiency and IgA deficiency, in Primary Immunodeficiency Diseases: A Molecular and Genetic Approach, H.D. Ochs, C.I.E. Smith, J.M. Puck, Eds. 1999, Oxford University Press: New York, pp. 205–262Google Scholar
  29. 29.
    Grimbacher B, Hutloff A, Schlesier M, et al. (2003) Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol 4(3): 261–268CrossRefPubMedGoogle Scholar
  30. 30.
    Braig D U, Schaffer A A, Glocker E, et al. (2003) Linkage of autosomal dominant common variable immunodeficiency to chromosome 5p and evidence for locus heterogeneity. Hum Genet 112(4): 369–378PubMedGoogle Scholar
  31. 31.
    Kralovicova J, Hammarstrom L, Plebani A, Webster AD, Vorechovsky I (2003) Fine-scale mapping at IGAD1 and genome-wide genetic linkage analysis implicate HLA-DQ/DR as a major susceptibility locus in selective IgA deficiency and common variable immunodeficiency. J Immunol 170(5): 2765–2775PubMedGoogle Scholar
  32. 32.
    Dalal I, Reid B, Nisbet-Brown E, Roifman C (1998) The outcome of patients with hypogamr-naglobulinemia in infancy and early childhood. J Pediatr 133: 144–146CrossRefPubMedGoogle Scholar
  33. 33.
    Siegel R, Issekutz T, Schwaber J, Rosen F, Geha R (1981) Deficiency of T helper cells in transient hypogamrnaglobulinemia of infancy. N Engl J Med 305: 1307–1313PubMedGoogle Scholar
  34. 34.
    Kilic S, Tezcan I, Sonal, Metin A, Ersoy F (2000) Transient hypogammaglobulinemia of infancy: clinical and immunologic features of 40 new cases. Pediatrics International 42: 647–650CrossRefPubMedGoogle Scholar
  35. 35.
    McGeady S J (1987) Transient hypogammaglobulinemia of infancy: need to reconsider name and definition. J Pediatr 110: 47–50CrossRefPubMedGoogle Scholar
  36. 36.
    Kornfeld S J, Kratz J, Haire R N, Litman G W, Good R A (1995) X-linked agammaglobulinemia presenting as transient hypogammaglobulinemia of infancy. J Allergy Clin Immunol 95: 915–917CrossRefPubMedGoogle Scholar
  37. 37.
    Schoaffer F, Monteiro R, Volanakis J, Cooper M (1991) IgA deficiency. Immunodeficiency Rev 3: 15–44Google Scholar
  38. 38.
    Fasth A (1982) Primary immunodeficiency disorders in Sweden: Cases among children 1974–1979. J Clin Immunol 2: 86–92CrossRefPubMedGoogle Scholar
  39. 39.
    Aucouturier P, Lacombe C, Bremard C, et al. (1989) Clin Immunol Immunopathol 51: 22–37CrossRefPubMedGoogle Scholar
  40. 40.
    Lefranc M P, Hammarstrom L, Smith C I, Lefranc G (1991) Gene deletions in the human immunoglobulin heavy chain constant region locus: molecular and immunological analysis. Immunol Rev 2: 265–281Google Scholar
  41. 41.
    Ohga S, Okada K, Asahi T, Ueda K, Sakiyama Y, Matsumoto S (1995) Recurrent pneumococ-cal meningitis in a patient with transient IgG subclass deficiency. Acta Paediatr Jpn 37: 196–200PubMedGoogle Scholar
  42. 42.
    Sorensen R U, Hidalgo H, Moore C, Leiva L E (1996) Antipneumococcal antibody titers and IgG subclasses in children with recurrent respiratory infections. Pediatr Pulmonol 22: 167–173CrossRefPubMedGoogle Scholar
  43. 43.
    Javier F C, Moore C M, Sorensen R U (2000) Distribution of primary immunodeficiency diseases diagnosed in a pediatric tertiary hospital. Ann Allergy Asthma Immunol 84: 25–30PubMedGoogle Scholar
  44. 44.
    Stanley P J, Corbo G, Cole P J (1984) Serum IgG subclasses in chronic and recurrent respiratory infections. Clin Exp Immunol 58: 703–708PubMedGoogle Scholar
  45. 45.
    Umetsu D T, Ambrosino D M, Quinti I, Siber G R, Geha R S (1985) Recurrent sinopulmonary infection and impaired antibody response to bacterial capsular polysaccharide antigen in children with selective IgG-subclass deficiency. N Engl J Med 313: 1247–1251PubMedCrossRefGoogle Scholar
  46. 46.
    Siber G R, Schur P H, Aisenberg A C, Weitzman S A, Schiffman G (1980) Correlation between serum IgG2 concentrations and the antibody response to bacterial polysaccharide antigens. N Engl J Med 303: 178–182PubMedCrossRefGoogle Scholar
  47. 47.
    Lim P L, Lau Y L (1994) Occurrence of IgG subclass antibodies to ovalbumin, avidin, and pneumococcal polysaccharide in children. Int Arch All Immunol 104: 137–143CrossRefGoogle Scholar
  48. 48.
    Sanders L A, Rijkers G T, Tenbergen-Meekes A-M, Voorhorst-Ogink M M, Zegers B J (1995) Immunoglobulin isotype-specific antibody responses to pneumococcal polysaccharide vaccine in patients with recurrent bacterial respiratory tract infections. Pediatr Res 37: 812–819CrossRefPubMedGoogle Scholar
  49. 49.
    Bird D, Duffy S, Isaacs D, Webster A D (1985) Reference ranges for IgG subclasses in preschool children. Arch Dis Child 60: 204–207CrossRefPubMedGoogle Scholar
  50. 50.
    Sorensen R U, Leiva L E, Giangrosso P A, et al. (1998) Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine. Pediatr Infect Dis J 17: 685–691CrossRefPubMedGoogle Scholar
  51. 51.
    Saxon A, Kobayashi R H, Stevens R H, Singer A D, Stiehm E R, Siegel S C (1980) In vitro analysis of humoral immunity in antibody deficiency with normal immunoglobulins. Clin Immunol Immunopathol 17: 235–244CrossRefPubMedGoogle Scholar
  52. 52.
    French M A H, Harrison G (1984) Systemic antibody deficiency in patients without serum immunoglobulin deficiency or with selectivie IgA deficiency. Clin Exp Immunol 56: 18–22PubMedGoogle Scholar
  53. 53.
    Ambrosino D M, Siber G R, Chilmonczyk J B, Jernberg J B, Finberg R W (1987) An immunodeficiency characterized by impaired antibody responses to polysaccharide. N Engl J Med 316: 790–793PubMedCrossRefGoogle Scholar
  54. 54.
    Sorensen R U, Leiva L E, Javier F C, et al. (1998) Influence of age on the response to Streptococcus pneumoniae vaccine in patients with recurrent infections and normal immuno-globulin concentrations. J Allergy Clin Immunol 102: 215–221CrossRefPubMedGoogle Scholar
  55. 55.
    Hidalgo H, Moore C, Leiva L E, Sorensen R U (1996) Preimmunization and postimmuniza-tion pneumococcal antibody titers in children with recurrent infections. Ann Allergy 76: 341–346CrossRefGoogle Scholar
  56. 56.
    Stryk S, Siegfried E, Knutsen A (1999) Selective antibody deficiency to bacterial polysac-charide antigens in patients with Netherton syndrome. Pediatr Dermatol 16(1): 19–22CrossRefPubMedGoogle Scholar
  57. 57.
    Ortigas A P, Leiva L E, Moore C, Bradford N, Sorensen R U (1999) Natural history of specific antibody deficiency after IgG replacement therapy. Ann Allergy Asthma Immunol 82: 71Google Scholar
  58. 58.
    Burks A, Sampson HA, Buckley RH (1986) Anaphylactic reactions after gamma globulin administration in patients with hypogamma-globulinemia: detection of IgE antibodies to IgA. N Engl J Med 314(9): 560–564PubMedCrossRefGoogle Scholar
  59. 59.
    Nelson R P, Ballow M (2003) Immunomodulation and immunotherapy: drugs, cytokines, cytokine receptors, and antibodies. J Allergy Clin Immunol 111: 720–732CrossRefGoogle Scholar
  60. 60.
    Quartier P, Debre M, De Blic J, et al. (1999) Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients. J Pediatr 134: 589–597CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Kenneth Paris
    • 1
    • 2
  • Lily Leiva
    • 3
    • 4
  • Ricardo U. Sorensen
    • 5
    • 6
  1. 1.Department of PediatricsResearch Institute for Children 4th Floor, Louisiana State University Health Sciences CenterUSA
  2. 2.Jeffrey Modell Diagnostic CenterChildren's HospitalNew OrleansUSA
  3. 3.Department of PediatricsResearch Institute for Children 4th Floor, Louisiana State University Health Sciences CenterUSA
  4. 4.Jeffrey Modell Diagnostic CenterChildren's HospitalNew OrleansUSA
  5. 5.Department of PediatricsResearch Institute for Children 4th Floor, Louisiana State University Health Sciences CenterUSA
  6. 6.Jeffrey Modell Diagnostic CenterChildren's HospitalNew OrleansUSA

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