Antibody Deficiencies

Kimberly C. Gilmour; Anita Chandra; D.S. Kumararatne

doi:10.1128/9781555818722.ch76

Chapter 76 : Antibody Deficiencies

Authors: Kimberly C. Gilmour¹, Anita Chandra², D.S. Kumararatne³

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Affiliations: 1: Immunology, Camelia Botnar Laboratories, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom; 2: Department of Clinical Biochemistry and Immunology, Box 109, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom; 3: Department of Clinical Biochemistry and Immunology, Box 109, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom

Content Type: Reference

Publication Year: 2016

Category: Immunology

Book DOI: 10.1128/9781555818722

Chapter DOI: 10.1128/9781555818722.ch76

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Abstract:

Antibody deficiency can be defined as a condition characterized by a reduction in serum immunoglobulin concentrations below the fifth centile for age. Antibody deficiency may affect all classes of immunoglobulins or may be confined to a single isotype.

Citation: Gilmour K, Chandra A, Kumararatne D. 2016. Antibody Deficiencies, p 737-748. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch76

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Antibody Deficiencies

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FIGURE 1

Investigation of possible antibody deficiency. This picture shows laboratory investigations in patients suspected of antibody deficiency.

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FIGURE 1

Investigation of possible antibody deficiency. This picture shows laboratory investigations in patients suspected of antibody deficiency.

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FIGURE 2

Extended B-cell immunophenotyping. The FACS plots demonstrate the gating strategy for B-cell immunophenotyping. Lymphocytes are gated based on forward (FSC) versus side scatter (SSC) (panel 1). The lymphocyte population is then used to gate B cells (CD19 versus side scatter) (panel 2). Using quadrants, naive B cells are defined as IgD+/CD27−, IgD+/CD27+ are non-switched memory B cells, and IgD−/CD27+ are switched memory B cells (panel 3). Transitional B cells are defined as IgM++CD38+ and IgM-CD38+ B cells and plasmablasts as IgM-CD38+ (panel 4). CD21low/CD38low B cells are indicated in panel 5. The presence of double-positive B cells greatly decreases the possibility of mutations in the AID gene, and they are used for back gating to confirm the IgM status of naive, switched, and non-switched memory B cells.

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FIGURE 2

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FIGURE 3

CD40L expression. Lymphocytes are defined by CD45 versus SSC. Prior to stimulation, there is limited CD25 and CD40L (CD154) expression (“Unstim” panels). Post stimulation in healthy individuals, there is an increase in both CD40L and CD25 expression (middle “Stim” panels). In patients with XHIM, although there is significant upregulation of CD25 (bottom right “Stim” panel), there is no increase in CD40L expression (top right “Stim” panel).

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FIGURE 3

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FIGURE 4

BTK analysis by FACs. Monocytes are gated by CD14+ versus SSC. Histograms showing isotype staining and BTK staining are then overlaid. Many hypomorphic mutations in BTK show a partial overlay as shown in the patient sample.

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FIGURE 4

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FIGURE 5

XIAP and SAP by FACs. Lymphocytes are defined based on FSC vs. SSC (panel 1). CD8+ T cells are then gated based on CD3+/CD8+ (panel 2). Isotype, XIAP (green), and SAP (pink) are analyzed as overlaid histograms (panel 3), where the XIAP shift about 1 log and the SAP about 2 logs. An XLP2 patient lacks XIAP (panel 4). An XLP1 patient lacks SAP (panel 5).

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FIGURE 5

References

/content/book/10.1128/9781555818722.ch76

1. Orange JS, Ballow M, Stiehm ER, Ballas ZK, Chinen J, De La Morena M, Kumararatne D, Harville TO, Hesterberg P, Koleilat M, McGhee S, Perez EE, Raasch J, Scherzer R, Schroeder H, Seroogy C, Huissoon A, Sorensen RU, Katial R. 2012. Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol 130( Suppl) : S1– S24.[CrossRef].[PubMed]

2. Vetrie D, Vorechovský I, Sideras P, Holland J, Davies A, Flinter F, Hammarström L, Kinnon C, Levinsky R, Bobrow M , et al 1993. The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature 361 : 226– 233.[CrossRef].[PubMed]

3. Yel L, Minegishi Y, Coustan-Smith E, Buckley RH, Trübel H, Pachman LM, Kitchingman GR, Campana D, Rohrer J, Conley ME. 1996. Mutations in the mu heavy-chain gene in patients with agammaglobulinemia. N Engl J Med 335 : 1486– 1493.[CrossRef].[PubMed]

4. Minegishi Y, Coustan-Smith E, Wang YH, Cooper MD, Campana D, Conley ME. 1998. Mutations in the human lambda5/14.1 gene result in B cell deficiency and agammaglobulinemia. J Exp Med 187 : 71– 77.[PubMed].[CrossRef]

5. Minegishi Y, Hendershot LM, Conley ME. 1999. Novel mechanisms control the folding and assembly of lambda5/14.1 and VpreB to produce an intact surrogate light chain. Proc Natl Acad Sci USA 96 : 3041– 3046.[PubMed].[CrossRef]

6. Ferrari S, Lougaris V, Caraffi S, Zuntini R, Yang J, Soresina A, Meini A, Cazzola G, Rossi C, Reth M, Plebani A. 2007. Mutations of the Igbeta gene cause agammaglobulinemia in man. J Exp Med 204 : 2047– 2051.[CrossRef].[PubMed]

7. Minegishi Y, Rohrer J, Coustan-Smith E, Lederman HM, Pappu R, Campana D, Chan AC, Conley ME. 1999. An essential role for BLNK in human B cell development. Science 286 : 1954– 1957.[PubMed].[CrossRef]

8. Korthäuer U, Graf D, Mages HW, Brière F, Padayachee M, Malcolm S, Ugazio AG, Notarangelo LD, Levinsky RJ, Kroczek RA. 1993. Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM. Nature 361 : 539– 541.[CrossRef].[PubMed]

9. Ferrari S, Giliani S, Insalaco A, Al-Ghonaium A, Soresina AR, Loubser M, Avanzini MA, Marconi M, Badolato R, Ugazio AG, Levy Y, Catalan N, Durandy A, Tbakhi A, Notarangelo LD, Plebani A. 2001. Mutations of CD40 gene cause an autosomal recessive form of immunodeficiency with hyper IgM. Proc Natl Acad Sci USA 98 : 12614– 12619.[CrossRef].[PubMed]

10. Angulo I, Vadas O, Garçon F, Banham-Hall E, Plagnol V, Leahy TR, Baxendale H, Coulter T, Curtis J, Wu C, Blake-Palmer K, Perisic O, Smyth D, Maes M, Fiddler C, Juss J, Cilliers D, Markelj G, Chandra A, Farmer G, Kielkowska A, Clark J, Kracker S, Debré M, Picard C, Pellier I, Jabado N, Morris JA, Barcenas-Morales G, Fischer A, Stephens L, Hawkins P, Barrett JC, Abinun M, Clatworthy M, Durandy A, Doffinger R, Chilvers ER, Cant AJ, Kumararatne D, Okkenhaug K, Williams RL, Condliffe A, Nejentsev S. 2013. Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage. Science 342 : 866– 871.[CrossRef].[PubMed]

11. Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, Vlkova M, Hernandez M, Detkova D, Bos PR, Poerksen G, von Bernuth H, Baumann U, Goldacker S, Gutenberger S, Schlesier M, Bergeron-van der Cruyssen F, Le Garff M, Debré P, Jacobs R, Jones J, Bateman E, Litzman J, van Hagen PM, Plebani A, Schmidt RE, Thon V, Quinti I, Espanol T, Webster AD, Chapel H, Vihinen M, Oksenhendler E, Peter HH, Warnatz K. 2008. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood 111 : 77– 85.[CrossRef].[PubMed]

12. Morbach H, Eichhorn EM, Liese JG, Girschick HJ. 2010. Reference values for B cell subpopulations from infancy to adulthood. Clin Exp Immunol 162 : 271– 279.[CrossRef].[PubMed]

13. Gilmour KC, Walshe D, Heath S, Monaghan G, Loughlin S, Lester T, Norbury G, Cale CM. 2003. Immunological and genetic analysis of 65 patients with a clinical suspicion of X-linked hyper-IgM. Mol Pathol 56 : 256– 262.[PubMed].[CrossRef]

14. van El CG, Cornel MC, Borry P, Hastings RJ, Fellmann F, Hodgson SV, Howard HC, Cambon-Thomsen A, Knoppers BM, Meijers-Heijboer H, Scheffer H, Tranebjaerg L, Dondorp W, de Wert GM ESHG Public and Professional Policy Committee. 2013. Whole-genome sequencing in health care. Recommendations of the European Society of Human Genetics. Eur J Hum Genet 21( Suppl 1) : S1– S5.[PubMed]

15. Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G. 2002. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30 : e57.[PubMed].[CrossRef]

16. Ram G, Chinen J. 2011. Infections and immunodeficiency in Down syndrome. Clin Exp Immunol 164 : 9– 16.[CrossRef].[PubMed]

17. Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM. 2013. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 369 : 1502– 1511.[CrossRef].[PubMed]

18. Minegishi Y, Coustan-Smith E, Rapalus L, Ersoy F, Campana D, Conley ME. 1999. Mutations in Igalpha (CD79a) result in a complete block in B-cell development. J Clin Invest 104 : 1115– 1121.[CrossRef].[PubMed]

19. Conley ME, Dobbs AK, Quintana AM, Bosompem A, Wang Y-D, Coustan-Smith E, Smith AM, Perez EE, Murray PJ. 2012. Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K. J Exp Med 209 : 463– 470.[CrossRef].[PubMed]

20. van Zelm MC, Reisli I, van der Burg M, Castaño D, van Noesel CJ, van Tol MJ, Woellner C, Grimbacher B, Patiño PJ, van Dongen JJ, Franco JL. 2006. An antibody-deficiency syndrome due to mutations in the CD19 gene. N Engl J Med 354 : 1901– 1912.[CrossRef].[PubMed]

21. Kuijpers TW, Bende RJ, Baars PA, Grummels A, Derks IAM, Dolman KM, Beaumont T, Tedder TF, van Noesel CJM, Eldering E, van Lier RAW. 2010. CD20 deficiency in humans results in impaired T cell-independent antibody responses. J Clin Invest 120 : 214– 222.[CrossRef].[PubMed]

22. Thiel J, Kimmig L, Salzer U, Grudzien M, Lebrecht D, Hagena T, Draeger R, Voelxen N, Bergbreiter A, Jennings S, Gutenberger S, Aichem A, Illges H, Hannan JP, Kienzler A-K, Rizzi M, Eibel H, Peter H-H, Warnatz K, Grimbacher B, Rump J-A, Schlesier M. 2012. Genetic CD21 deficiency is associated with hypogammaglobulinemia. J Allergy Clin Immunol 129 : 801– 810.e6.[CrossRef].[PubMed]

23. van Zelm MC, Smet J, Adams B, Mascart F, Schandené L, Janssen F, Ferster A, Kuo C-C, Levy S, van Dongen JJM, van der Burg M. 2010. CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J Clin Invest 120 : 1265– 1274.[CrossRef].[PubMed]

24. Xu GL, Bestor TH, Bourc'his D, Hsieh CL, Tommerup N, Bugge M, Hulten M, Qu X, Russo JJ, Viegas-Péquignot E. 1999. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402 : 187– 191.[CrossRef].[PubMed]

25. de Greef JC, Wang J, Balog J, den Dunnen JT, Frants RR, Straasheijm KR, Aytekin C, van der Burg M, Duprez L, Ferster A, Gennery AR, Gimelli G, Reisli I, Schuetz C, Schulz A, Smeets DF, Sznajer Y, Wijmenga C, van Eggermond MC, van Ostaijen-Ten Dam MM, Lankester AC, van Tol MJ, van den Elsen PJ, Weemaes CM, van der Maarel SM. 2011. Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2. Am J Hum Genet 88 : 796– 804.[CrossRef].[PubMed]

26. Grimbacher B, Hutloff A, Schlesier M, Glocker E, Warnatz K, Dräger R, Eibel H, Fischer B, Schäffer AA, Mages HW, Kroczek RA, Peter HH. 2003. Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol 4 : 261– 268.[CrossRef].[PubMed]

27. Sayos J, Wu C, Morra M, Wang N, Zhang X, Allen D, van Schaik S, Notarangelo L, Geha R, Roncarolo MG, Oettgen H, De Vries JE, Aversa G, Terhorst C. 1998. The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM. Nature 395 : 462– 469.[CrossRef].[PubMed]

28. Rigaud S, Fondanèche M-C, Lambert N, Pasquier B, Mateo V, Soulas P, Galicier L, Le Deist F, Rieux-Laucat F, Revy P, Fischer A, de Saint Basile G, Latour S. 2006. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. Nature 444 : 110– 114.[CrossRef].[PubMed]

29. Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS. 2005. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet 37 : 829– 834.[CrossRef].[PubMed]

30. Warnatz K, Salzer U, Rizzi M, Fischer B, Gutenberger S, Böhm J, Kienzler A-K, Pan-Hammarström Q, Hammarström L, Rakhmanov M, Schlesier M, Grimbacher B, Peter H-H, Eibel H. 2009. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans. Proc Natl Acad Sci USA 106 : 13945– 13950.[CrossRef].[PubMed]

31. Revy P, Muto T, Levy Y, Geissmann F, Plebani A, Sanal O, Catalan N, Forveille M, Dufourcq-Labelouse R, Gennery A, Tezcan I, Ersoy F, Kayserili H, Ugazio AG, Brousse N, Muramatsu M, Notarangelo LD, Kinoshita K, Honjo T, Fischer A, Durandy A. 2000. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 102 : 565– 575.[PubMed].[CrossRef]

32. Imai K, Slupphaug G, Lee W-I, Revy P, Nonoyama S, Catalan N, Yel L, Forveille M, Kavli B, Krokan HE, Ochs HD, Fischer A, Durandy A. 2003. Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nat Immunol 4 : 1023– 1028.[CrossRef].[PubMed]

33. Péron S, Metin A, Gardès P, Alyanakian MA, Sheridan E, Kratz CP, Fischer A, Durandy A. 2008. Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination. J Exp Med 205 : 2465– 2472.[CrossRef].[PubMed]

34. Stepensky P, Keller B, Buchta M, Kienzler A-K, Elpeleg O, Somech R, Cohen S, Shachar I, Miosge LA, Schlesier M, Fuchs I, Enders A, Eibel H, Grimbacher B, Warnatz K. 2013. Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects. J Allergy Clin Immunol 131 : 477– 485.e1.[CrossRef].[PubMed]

35. Boisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z, Abhyankar A, Israël L, Trevejo-Nunez G, Bogunovic D, Cepika A-M, MacDuff D, Chrabieh M, Hubeau M, Bajolle F, Debré M, Mazzolari E, Vairo D, Agou F, Virgin HW, Bossuyt X, Rambaud C, Facchetti F, Bonnet D, Quartier P, Fournet J-C, Pascual V, Chaussabel D, Notarangelo LD, Puel A, Israël A, Casanova J-L, Picard C. 2012. Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat Immunol 13 : 1178– 1186[CrossRef].[PubMed]

36. Döffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A, Bodemer C, Kenwrick S, Dupuis-Girod S, Blanche S, Wood P, Rabia SH, Headon DJ, Overbeek PA, Le Deist F, Holland SM, Belani K, Kumararatne DS, Fischer A, Shapiro R, Conley ME, Reimund E, Kalhoff H, Abinun M, Munnich A, Israël A, Courtois G, Casanova JL. 2001. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet 27 : 277– 285.[CrossRef].[PubMed]

37. Courtois G, Smahi A, Reichenbach J, Döffinger R, Cancrini C, Bonnet M, Puel A, Chable-Bessia C, Yamaoka S, Feinberg J, Dupuis-Girod S, Bodemer C, Livadiotti S, Novelli F, Rossi P, Fischer A, Israël A, Munnich A, Le Deist F, Casanova J-L. 2003. A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency. J Clin Invest 112 : 1108– 1115.[CrossRef].[PubMed]

Tables

Antibody Deficiencies

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TABLE 1

The main phenotypes of primary antibody deficiencies a

TABLE 1

The main phenotypes of primary antibody deficiencies a

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TABLE 2

Inheritance of antibody deficiencies

TABLE 2

Inheritance of antibody deficiencies