Utility of Peripheral Blood B Cell Subsets Analysis in Common Variable Immunodeficiency

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2012 Jan 13

PMID 22236004

Citations 12

Authors

M Al Kindi

J Mundy

T Sullivan

W Smith

F Kette

A Smith

R Heddle

P Hissaria

Affiliations

Soon will be listed here.

Abstract

Abnormalities in peripheral blood B cell subsets have been identified in common variable immunodeficiency (CVID) patients and classification systems based upon their numbers have been proposed to predict the clinical features. We analysed B lymphocyte subsets by multi-colour flow cytometry (MFC) in a cohort of well-characterized CVID patients to look at their clinical relevance and validate the published association of different classification criteria (Freiburg, Paris and Euroclass) with clinical manifestations. CVID patients had a reduced proportion of total and switched memory B cells (MBC, swMBC) compared to normal controls (P < 0·0006). Patients classified in Freiburg Ia had a higher prevalence of granulomatous diseases (P = 0·0034). The previously published associations with autoimmune diseases could not be confirmed. The Euroclass classification was not predictive of clinical phenotypes. The absolute numbers of all B cell subsets were reduced in CVID patients compared to controls. There was a significant linear correlation between low absolute total B cells and MBC with granulomatous disease (P < 0·05) and a trend towards lower B cells in patients with autoimmune diseases (P = 0·07). Absolute number of different B cell subsets may be more meaningful than their relative percentages in assessing the risk of granulomatous diseases and possibly autoimmunity.

Citing Articles

B Cell Subsets in Colombian Adults with Predominantly Antibody Deficiencies, Bronchiectasis or Recurrent Pneumonia.

Giraldo-Ocampo S, Bonelo A, Zea-Vera A Adv Respir Med. 2022; 90(4):254-266.

PMID: 36004955 PMC: 9717342. DOI: 10.3390/arm90040035.

Lymphocyte Subgroups and KREC Numbers in Common Variable Immunodeficiency: A Single Center Study.

Yaz I, Ozbek B, Ng Y, Cetinkaya P, Oskay Halacli S, Tan C J Clin Immunol. 2020; 40(3):494-502.

PMID: 32056073 DOI: 10.1007/s10875-020-00761-2.

Common Variable Immunodeficiency and Liver Involvement.

Song J, Lleo A, Yang G, Zhang W, Bowlus C, Gershwin M Clin Rev Allergy Immunol. 2017; 55(3):340-351.

PMID: 28785926 PMC: 5803456. DOI: 10.1007/s12016-017-8638-z.

The immunophenotypic fingerprint of patients with primary antibody deficiencies is partially present in their asymptomatic first-degree relatives.

Bogaert D, De Bruyne M, Debacker V, Depuydt P, De Preter K, Bonroy C Haematologica. 2016; 102(1):192-202.

PMID: 27634199 PMC: 5210250. DOI: 10.3324/haematol.2016.149112.

The B-cell compartment in antibody-deficient infants and young children - developing common variable immunodeficiency or transient immune maturation?.

Szczawinska-Poplonyk A, Tapolska-Jozwiak K, Samara H Ital J Pediatr. 2016; 42(1):71.

PMID: 27461226 PMC: 4962439. DOI: 10.1186/s13052-016-0279-y.

References

Mouillot G, Carmagnat M, Gerard L, Garnier J, Fieschi C, Vince N . B-cell and T-cell phenotypes in CVID patients correlate with the clinical phenotype of the disease. J Clin Immunol. 2010; 30(5):746-55. DOI: 10.1007/s10875-010-9424-3. View

Eades-Perner A, Gathmann B, Knerr V, Guzman D, Veit D, Kindle G . The European internet-based patient and research database for primary immunodeficiencies: results 2004-06. Clin Exp Immunol. 2007; 147(2):306-12. PMC: 1810463. DOI: 10.1111/j.1365-2249.2006.03292.x. View

Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E . The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2007; 111(1):77-85. DOI: 10.1182/blood-2007-06-091744. View

Warnatz K, Schlesier M . Flowcytometric phenotyping of common variable immunodeficiency. Cytometry B Clin Cytom. 2008; 74(5):261-71. DOI: 10.1002/cyto.b.20432. View

Berglund L, Wong S, Fulcher D . B-cell maturation defects in common variable immunodeficiency and association with clinical features. Pathology. 2008; 40(3):288-94. DOI: 10.1080/00313020801911470. View

Yong P, Orange J, Sullivan K . Pediatric common variable immunodeficiency: immunologic and phenotypic associations with switched memory B cells. Pediatr Allergy Immunol. 2010; 21(5):852-8. DOI: 10.1111/j.1399-3038.2010.01004.x. View

Rezaei N, Aghamohammadi A, Moin M, Pourpak Z, Movahedi M, Gharagozlou M . Frequency and clinical manifestations of patients with primary immunodeficiency disorders in Iran: update from the Iranian Primary Immunodeficiency Registry. J Clin Immunol. 2006; 26(6):519-32. DOI: 10.1007/s10875-006-9047-x. View

Warnatz K, Denz A, Drager R, Braun M, Groth C, Wolff-Vorbeck G . Severe deficiency of switched memory B cells (CD27(+)IgM(-)IgD(-)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood. 2002; 99(5):1544-51. DOI: 10.1182/blood.v99.5.1544. View

Kaveri S, Maddur M, Hegde P, Lacroix-Desmazes S, Bayry J . Intravenous immunoglobulins in immunodeficiencies: more than mere replacement therapy. Clin Exp Immunol. 2011; 164 Suppl 2:2-5. PMC: 3087903. DOI: 10.1111/j.1365-2249.2011.04387.x. View

10.

Pirzada Y, Khuder S, Donabedian H . Predicting AIDS-related events using CD4 percentage or CD4 absolute counts. AIDS Res Ther. 2006; 3:20. PMC: 1570471. DOI: 10.1186/1742-6405-3-20. View

11.

Losi C, Silini A, Fiorini C, Soresina A, Meini A, Ferrari S . Mutational analysis of human BAFF receptor TNFRSF13C (BAFF-R) in patients with common variable immunodeficiency. J Clin Immunol. 2005; 25(5):496-502. DOI: 10.1007/s10875-005-5637-2. View

12.

Cooper M, Faulk W, Fudenberg H, GOOD R, HITZIG W, Kunkel H . Classification of primary immunodeficiencies. N Engl J Med. 1973; 288(18):966-7. DOI: 10.1056/NEJM197305032881814. View

13.

Salzer U, Chapel H, Webster A, Pan-Hammarstrom Q, Schmitt-Graeff A, Schlesier M . Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet. 2005; 37(8):820-8. DOI: 10.1038/ng1600. View

14.

Conley M, Notarangelo L, Etzioni A . Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999; 93(3):190-7. DOI: 10.1006/clim.1999.4799. View

15.

Grimbacher B, Hutloff A, Schlesier M, Glocker E, Warnatz K, Drager R . Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol. 2003; 4(3):261-8. DOI: 10.1038/ni902. View

16.

Cunningham-Rundles C, Bodian C . Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999; 92(1):34-48. DOI: 10.1006/clim.1999.4725. View

17.

Spickett G, Farrant J, North M, Zhang J, Morgan L, Webster A . Common variable immunodeficiency: how many diseases?. Immunol Today. 1997; 18(7):325-8. DOI: 10.1016/s0167-5699(97)01086-4. View

18.

Castigli E, Wilson S, Garibyan L, Rachid R, Bonilla F, Schneider L . TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005; 37(8):829-34. DOI: 10.1038/ng1601. View

19.

Kalina T, Stuchly J, Janda A, Hrusak O, Ruzickova S, Sediva A . Profiling of polychromatic flow cytometry data on B-cells reveals patients' clusters in common variable immunodeficiency. Cytometry A. 2009; 75(11):902-9. DOI: 10.1002/cyto.a.20801. View

20.

Piqueras B, Lavenu-Bombled C, Galicier L, Bergeron-van der Cruyssen F, Mouthon L, Chevret S . Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J Clin Immunol. 2003; 23(5):385-400. DOI: 10.1023/a:1025373601374. View