Zusammenfassung
Die Basisdiagnostik bei Verdacht auf Immundefekt soll die meisten lebensbedrohlichen und häufige immunologische Erkrankungen detektieren. Sie umfasst ein mikroskopisch differenziertes Blutbild und die Bestimmung von IgG, IgA, IgM und IgE (Ig: Immunglobulin). Ein SCID („severe combined immunodeficiency“) kann oft bereits anhand der meist (aber nicht immer!) vorhandenen Lymphopenie und dem Mangel an IgM diagnostiziert werden. Für CVID („common variable immunodeficiency“) sprechen ein persistierender IgG-Mangel nach Abschluss des 2. Lebensjahrs, ausgeschlossene sekundäre Ursachen des Antikörpermangels, 2 von 3 reduzierte Immunglobulinklassen und reduzierte Impfantikörpertiter. Durch diese immunologische Basisdiagnostik lassen sich vermutlich nur 40–50% der bisher bekannten Immundefekte erkennen. Die am klinischen Bild (Erreger, Art, Schwere und Verlauf der Infektion, syndromale Manifestationen, Zeichen einer gestörten Immunregulation) und den Ergebnissen der Basisdiagnostik ausgerichtete erweiterte immunologische Diagnostik ermöglicht eine Eingrenzung des Immundefekts. Die exakte Beschreibung des klinisch-immunologischen Phänotyps ist Voraussetzung für eine gezielte molekulargenetische Diagnostik.
Abstract
The basic diagnostic assessment of primary immunodeficiencies should allow recognition of most life-threatening and common conditions. This consists of a microscopic differential blood count and determination of immunoglobulin levels of IgG, IgA, IgM and IgE. Patients with severe combined immunodeficiency (SCID) often, but not always, present with lymphopenia and lack of IgM. Patients with a persistent lack of IgG, IgA and/or IgM and antibodies against recall antigens beyond the second year of life are suspected of having common variable immunodeficiency (CVID) if secondary causes for immunoglobulin loss can be excluded. This basic work-up will identify only 40–50% of primary immunodeficiencies. Advanced diagnostic work-up is based on findings such as isolated pathogens, severity and course of infections, syndrome manifestations and signs of immune dysregulation. Advanced work-up aims to narrow down the defect to a specific part of the immune system on a phenotypic level. The precise description of the clinical and immunological phenotype is a prerequisite to identify the underlying molecular defect.
This is a preview of subscription content, log in via an institution to check access.
Literatur
Albert MH, Notarangelo LD, Ochs HD (2010) Clinical spectrum, pathophysiology and treatment of the Wiskott-Aldrich syndrome. Curr Opin Hematol Nov 11. [Epub ahead of print]
Baumann U, Niehues T (2011) Infektanfälligkeit – Verdachtsmoment für Immundefekte. Monatsschr Kinderheilkd 5
Booth C, Gilmour KC, Veys P et al (2011) X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease. Blood 117:53–62
Boztug K, Klein C (2011) Genetic etiologies of severe congenital neutropenia. Curr Opin Pediatr 23:21–26
Bustamante J, Zhang SY, Bernuth H von et al (2008) From infectious diseases to primary immunodeficiencies. Immunol Allergy Clin North Am 28:235–258, vii
Cardenes M, Bernuth H von, Garcia-Saavedra A et al (2006) Autosomal recessive interleukin-1 receptor-associated kinase 4 deficiency in fourth-degree relatives. J Pediatr 148:549–551
Casrouge A, Zhang SY, Eidenschenk C et al (2006) Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 314:308–312
Ehl S, Schwarz K, Enders A et al (2005) A variant of SCID with specific immune responses and predominance of gamma delta T cells. J Clin Invest 115:3140–3148
Etzioni A (2010) Defects in the leukocyte adhesion cascade. Clin Rev Allergy Immunol 38:54–60
Fraitag S, Bodemer C (2010) Neonatal erythroderma. Curr Opin Pediatr 22:438–444
Glocker E, Ehl S, Grimbacher B (2007) Common variable immunodeficiency in children. Curr Opin Pediatr 19:685–692
Glocker E, Grimbacher B (2010) Chronic mucocutaneous candidiasis and congenital susceptibility to Candida. Curr Opin Allergy Clin Immunol 10:542–550
Hennewig U, Schulz A, Adams O et al (2007) Severe combined immunodeficiency signalized by eosinophilia and lymphopenia in rotavirus infected infants. Klin Padiatr 219:343–347
Honig M, Schwarz K (2006) Omenn syndrome: a lack of tolerance on the background of deficient lymphocyte development and maturation. Curr Opin Rheumatol 18:383–388
Kuhl JS, Schwarz K, Munch A et al (2011) Hyperbilirubinemia and rapid fatal hepatic failure in severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA-SCID). Klin Padiatr Jan 26. [Epub ahead of print]
Niehues T, Perez-Becker R, Schuetz C (2010) More than just SCID – the phenotypic range of combined immunodeficiencies associated with mutations in the recombinase activating genes (RAG) 1 and 2. Clin Immunol 135:183–192
Pachlopnik Schmid J, Canioni D, Moshous D et al (2011) Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency). Blood 117:1522–1529
Perez de Diego R, Sancho-Shimizu V, Lorenzo L et al (2010) Human TRAF3 adaptor molecule deficiency leads to impaired toll-like receptor 3 response and susceptibility to herpes simplex encephalitis. Immunity 33:400–411
Renner ED, Hartl D, Rylaarsdam S et al (2009) Comel-Netherton syndrome defined as primary immunodeficiency. J Allergy Clin Immunol 124:536–543
Rossberg S, Schwarz K, Meisel C et al (2009) Delayed onset of (severe) combined immunodeficiency (S)CID (T−B+NK+): complete IL-7 receptor deficiency in a 22 months old girl. Klin Padiatr 221:339–343
Schimke LF, Sawalle-Belohradsky J, Roesler J et al (2010) Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from atopic dermatitis. J Allergy Clin Immunol 126:611–7.e1
Schuetz C, Huck K, Gudowius S et al (2008) An immunodeficiency disease with RAG mutations and granulomas. N Engl J Med 358:2030–2038
Seger RA (2010) Chronic granulomatous disease: recent advances in pathophysiology and treatment. Neth J Med 68:334–340
Somech R, Simon AJ, Lev A et al (2009) Reduced central tolerance in Omenn syndrome leads to immature self-reactive oligoclonal T cells. J Allergy Clin Immunol 124:793–800
Stepensky P, Weintraub M, Yanir A et al (2010) IL-2-inducible T cell kinase deficiency: clinical presentation and therapeutic approach. Haematologica 96(3):472–476
Van Zelm MC, Reisli I, Van der Burg M et al (2006) An antibody-deficiency syndrome due to mutations in the CD19 gene. N Engl J Med 354:1901–1912
Villa A, Notarangelo LD, Roifman CM (2008) Omenn syndrome: inflammation in leaky severe combined immunodeficiency. J Allergy Clin Immunol 122:1082–1086
Wahn U, Seger R, Wahn V, Holländer GA (2005) Pädiatrische Allergologie und Immunologie, 4. Aufl. Urban & Fischer, Elsevier, München Jena
Interessenkonflikt
Der korrespondierende Autor weist auf folgende Beziehungen hin: Horst von Bernuth war in 2011 Referent für CSL Plasma im Rahmen einer Forbildung für Plasmaspender.
Stephan Ehl erhielt Vortragshonorare von CSL Behring und Baxter.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
von Bernuth, H., Schwarz, K., Renner, E. et al. Diagnostik primärer Immundefekte. Monatsschr Kinderheilkd 159, 434–442 (2011). https://doi.org/10.1007/s00112-010-2332-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00112-010-2332-z
Schlüsselwörter
- Basisdiagnostik
- Immunsystemerkrankungen
- SCID („severe combined immunodeficiency“)
- CVID („common variable immunodeficiency“)
- Molekulargenetische Diagnostik