Antibody deficiency and autoimmunity in 22q11.2 deletion syndrome (original) (raw)

Abstract

Background: Although severe T cell immunodeficiency in DiGeorge anomaly is rare, previous studies of humoral function in these patients have found no antibody abnormalities but have not examined the response to polysaccharide antigens. Isolated cases of autoimmunity have been reported. Several patients with 22q11.2 deletion attending our immunology clinic suffered recurrent sinopulmonary infection or autoimmune phenomena.

Aims: To investigate humoral immunodeficiency, particularly pneumococcal polysaccharide antibody deficiency, and autoimmune phenomena in a cohort of patients with 22q11.2 deletion.

Methods: A history of severe or recurrent infection and autoimmune symptoms were noted. Lymphocyte subsets, immunoglobulins, IgG subclasses, specific vaccine antibodies, and autoantibodies were measured. Subjects were vaccinated with appropriate antigens as indicated.

Results: Of 32 patients identified, 26 (81%) had severe or recurrent infection, of which 13 (50%) had abnormal serum immunoglobulin measurements and 11/20 ≥4 years old (55%) had an abnormal response to pneumococcal polysaccharide. Ten of 30 patients (33%) had autoimmune phenomena; six (20%) were symptomatic.

Conclusions: Humoral immunodeficiency is more common than previously recognised in patients with 22q11.2 deletion. Normal T cell function and immunoglobulin levels do not exclude poor specific antibody responses. Patients should be referred for formal immunological assessment of cellular and humoral immune function.

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Selected References

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  1. DePiero A. D., Lourie E. M., Berman B. W., Robin N. H., Zinn A. B., Hostoffer R. W. Recurrent immune cytopenias in two patients with DiGeorge/velocardiofacial syndrome. J Pediatr. 1997 Sep;131(3):484–486. doi: 10.1016/s0022-3476(97)80085-6. [DOI] [PubMed] [Google Scholar]
  2. Etzioni A., Pollack S. Autoimmune phenomena in DiGeorge syndrome. Isr J Med Sci. 1994 Nov;30(11):853–853. [PubMed] [Google Scholar]
  3. Griffioen A. W., Toebes E. A., Rijkers G. T., Claas F. H., Datema G., Zegers B. J. The amplifier role of T cells in the human in vitro B cell response to type 4 pneumococcal polysaccharide. Immunol Lett. 1992 May;32(3):265–272. doi: 10.1016/0165-2478(92)90060-2. [DOI] [PubMed] [Google Scholar]
  4. Griffiths H., Lea J., Bunch C., Lee M., Chapel H. Predictors of infection in chronic lymphocytic leukaemia (CLL). Clin Exp Immunol. 1992 Sep;89(3):374–377. doi: 10.1111/j.1365-2249.1992.tb06965.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gupta S., Aggarwal S., Nguyen T. Increased spontaneous apoptosis in T lymphocytes in DiGeorge anomaly. Clin Exp Immunol. 1998 Jul;113(1):65–71. doi: 10.1046/j.1365-2249.1998.00629.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hannet I., Erkeller-Yuksel F., Lydyard P., Deneys V., DeBruyère M. Developmental and maturational changes in human blood lymphocyte subpopulations. Immunol Today. 1992 Jun;13(6):215–218. doi: 10.1016/0167-5699(92)90157-3. [DOI] [PubMed] [Google Scholar]
  7. Junker A. K., Driscoll D. A. Humoral immunity in DiGeorge syndrome. J Pediatr. 1995 Aug;127(2):231–237. doi: 10.1016/s0022-3476(95)70300-4. [DOI] [PubMed] [Google Scholar]
  8. Kornfeld S. J., Zeffren B., Christodoulou C. S., Day N. K., Cawkwell G., Good R. A. DiGeorge anomaly: a comparative study of the clinical and immunologic characteristics of patients positive and negative by fluorescence in situ hybridization. J Allergy Clin Immunol. 2000 May;105(5):983–987. doi: 10.1067/mai.2000.105527. [DOI] [PubMed] [Google Scholar]
  9. Kourtis A. P., Ibegbu C. C., Lee F. K., Vogler L., Philips K., Nahmias A. J. Decreases in CD5+ B lymphocytes in children with the DiGeorge anomaly. Scand J Immunol. 1997 Sep;46(3):281–283. doi: 10.1046/j.1365-3083.1997.d01-127.x. [DOI] [PubMed] [Google Scholar]
  10. Käyhty H., Peltola H., Karanko V., Mäkelä P. H. The protective level of serum antibodies to the capsular polysaccharide of Haemophilus influenzae type b. J Infect Dis. 1983 Jun;147(6):1100–1100. doi: 10.1093/infdis/147.6.1100. [DOI] [PubMed] [Google Scholar]
  11. Ryan A. K., Goodship J. A., Wilson D. I., Philip N., Levy A., Seidel H., Schuffenhauer S., Oechsler H., Belohradsky B., Prieur M. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet. 1997 Oct;34(10):798–804. doi: 10.1136/jmg.34.10.798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Schubert M. S., Moss R. B. Selective polysaccharide antibody deficiency in familial DiGeorge syndrome. Ann Allergy. 1992 Sep;69(3):231–238. [PubMed] [Google Scholar]
  13. Smith C. A., Driscoll D. A., Emanuel B. S., McDonald-McGinn D. M., Zackai E. H., Sullivan K. E. Increased prevalence of immunoglobulin A deficiency in patients with the chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Diagn Lab Immunol. 1998 May;5(3):415–417. doi: 10.1128/cdli.5.3.415-417.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sullivan K. E., McDonald-McGinn D. M., Driscoll D. A., Zmijewski C. M., Ellabban A. S., Reed L., Emanuel B. S., Zackai E. H., Athreya B. H., Keenan G. Juvenile rheumatoid arthritis-like polyarthritis in chromosome 22q11.2 deletion syndrome (DiGeorge anomalad/velocardiofacial syndrome/conotruncal anomaly face syndrome). Arthritis Rheum. 1997 Mar;40(3):430–436. doi: 10.1002/art.1780400307. [DOI] [PubMed] [Google Scholar]