Serum B cell activating factor and interleukin 10 levels in common variable immunodeficiency: relationship with clinical findings

  • Radovan Mijanovic Clinic of Allergy and Immunology, Clinical Center of Serbia, Belgrade
  • Sladjana Andrejevic Clinic of Allergy and Immunology, Clinical Center of Serbia, Belgrade, Serbia; School of Medicine, University of Belgrade, Belgrade
  • Vladimir Jurisic Faculty of Medical Sciences, University of Kragujevac
  • Branka Bonaci-Nikolic Clinic of Allergy and Immunology, Clinical Center of Serbia, Belgrade, Serbia; School of Medicine, University of Belgrade
DOI: https://doi.org/10.2298/VSP161115068M
Ključne reči: common variable immunodeficiency, b-cell activating factor, cytokines, interleukins, lung diseases, splenomegaly, autoimmune diseases

Sažetak


Abstract

 

Background/Aim. Common variable immunodeficiency (CVID) is an immunologically and clinically heterogeneous disorder. Disturbed cytokine production is implicated in dys­functional immune response. The aim of this study was to in­vestigated B-cell activating factor (BAFF) and interleukin (IL)-10 levels in CVID patients. Methods. The study included 28 CVID patients diagnosed and followed during a 20-year period (mean follow-up 14.5 years). Control groups consisted of 4 pa­tients with X-linked agammaglobulinemia (XLA) and 21 healthy subjects. According to clinical characteristics, the CVID patients were divided into four groups which partly overlap: chronic pulmonary diseases (n = 21), splenomegaly (n = 13), autoimmune diseases (n = 9) and patients with recur­rent infections despite regular intravenous immunoglobulin (IVIg) substitution (n = 4). The serum levels of BAFF and IL-10 were measured by commercial ELISA. Results. The BAFF levels were found to be higher in all CVID patients compared to the healthy controls (p < 0.01). The most significant differ­ences were observed in the patients with pulmonary diseases and splenomegaly (p < 0.0001). Also, concentrations of IL-10 were higher in all CVID patients in comparison with the XLA patients (p < 0.05) and healthy subjects (p < 0.01). A statisti­cally significant positive correlation (r = 0.86; p < 0.01) was found between the levels of BAFF and IL-10 in the CVID pa­tients with autoimmune diseases. We demonstrated that the CVID patients with chronic pulmonary diseases had higher levels of IL-10, while the CVID patients with recurrent infec­tions had higher BAFF concentrations in comparison to the patients without these features (p < 0.05). Conclusion. In spite of the limited number of patients, this is the first report from Serbia, examining the serum levels of BAFF and IL-10 in the CVID patients. Our study showed significantly increased con­centrations of serum BAFF and IL-10 in the patients with CVID compared to the healthy subjects. Further studies are needed to confirm our findings that the BAFF levels are more pronounced in patients with recurrent infections while IL-10 levels are higher in patients with chronic pulmonary diseases.

Biografije autora

Radovan Mijanovic, Clinic of Allergy and Immunology, Clinical Center of Serbia, Belgrade
Internal intensive care unit, Emergency Center, specialist of Internal medicine, subspecialist of allergology and clinical immunology, Primarius
Vladimir Jurisic, Faculty of Medical Sciences, University of Kragujevac
Professor of Pathophysiology at the Faculty of Medical Sciences, University of Kragujevac
Branka Bonaci-Nikolic, Clinic of Allergy and Immunology, Clinical Center of Serbia, Belgrade, Serbia; School of Medicine, University of Belgrade
Professor of Internal medicine at the School of medicine, University of Belgrade

Reference

REFERENCES

Gathmann B, Mahlaoui N, Ceredih , Gerard L, Oksenhendler E, Warnatz K, et al. Clinical picture and treatment of 2212 pa-tients with common variable immunodeficiency. J Allergy Clin Immunol 2014; 134(1): 116‒26.

Chapel H, Lucas M, Patel S, Lee M, Cunningham-Rundles C, Resnick E, et al. Confirmation and improvement of criteria for clinical phenotyping in common variable immunodeficiency disorders in replicate cohorts. J Allergy Clin Immunol 2012; 130(5): 1197‒8.e9.

Bateman EA, Ayers L, Sadler R, Lucas M, Roberts C, Woods A, et al. T cell phenotypes in patients with common variable immunodeficiency disorders: associations with clinical phenotypes in comparison with other groups with recurrent infections. Clin Exp Immunol 2012; 170(2): 202‒11.

Varzaneh FN, Keller B, Unger S, Aghamohammadi A, Warnatz K, Rezaei N. Cytokines in common variable immunodeficiency as signs of immune dysregulation and potential therapeutic tar-gets: A review of the current knowledge. J Clin Immunol 2014; 34(5): 524‒43.

Mackay F, Browning JL. BAFF: A fundamental survival factor for B cells. Nat Rev Immunol 2002; 2(7): 465‒75.

Miyagaki T, Fujimoto M, Sato S. Regulatory B cells in human in-flammatory and autoimmune diseases: From mouse models to clinical research. Int Immunol 2015; 27(10): 495‒504.

Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24(1): 1‒8.

Rezaei N, Amirzargar AA, Shakiba Y, Mahmoudi M, Moradi B, Aghamohammadi A. Proinflammatory cytokine gene single nuc-leotide polymorphisms in common variable immunodeficien-cy. Clin Exp Immunol 2009; 155(1): 21‒7.

Kreuzaler M, Rauch M, Salzer U, Birmelin J, Rizzi M, Grimbacher B, et al. Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors. J Immunol 2012; 188(1): 497‒503.

Warnatz K, Salzer U, Rizzi M, Fischer B, Gutenberger S, Böhm J, et al. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans. Proc Natl Acad Sci U S A 2009; 106(33): 13945‒50.

Knight AK, Radigan L, Marron T, Langs A, Zhang L, Cun-ningham-Rundles C. High serum levels of BAFF, APRIL, and TACI in common variable immunodeficiency. Clin Immunol 2007; 124(2): 182‒9.

Jin R, Kaneko H, Suzuki H, Arai T, Teramoto T, Fukao T, et al. Age-related changes in BAFF and APRIL profiles and upregu-lation of BAFF and APRIL expression in patients with prima-ry antibody deficiency. Int J Mol Med 2008; 21(2): 233‒8.

Barbosa RR, Silva SL, Silva SP, Melo AC, Pereira-Santos CM, Barata JT, et al. Reduced BAFF-R and increased TACI expres-sion in common variable immunodeficiency. J Clin Immunol 2014; 34(5): 573‒83.

Vincent FB, Morand EF, Mackay F. BAFF and innate immuni-ty: New therapeutic targets for systemic lupus erythematosus. Immunol Cell Biol 2012; 90(3): 293‒303.

Hel Z, Huijbregts RP, Xu J, Nechvatalova J, Vlkova M, Litzman J. Altered serum cytokine signature in common variable immu-nodeficiency. J Clin Immunol 2014; 34(8): 971‒8.

Said EA, Dupuy FP, Trautmann L, Zhang Y, Shi Y, El-Far M, et al. Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infec-tion. Nat Med 2010; 16(4): 452‒9.

Petri M, Stohl W, Chatham W, McCune JW, Chevrier M, Ryel J, et al. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum 2008; 58(8): 2453‒9.

Mellor-Pita S, Citores MJ, Castejon R, Yebra-Bango M, Tutor-Ureta P, Rosado S, et al. Monocytes and T lymphocytes contribute to a predominance of interleukin 6 and interleukin 10 in systemic lupus erythematosus. Cytom B Clin Cytom. 2009; 76(4): 261‒70.

Kutukculer N, Gulez N, Karaca NE, Aksu G, Berdeli A. Three different classifications, B lymphocyte subpopulations, TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF13 (APRIL) gene mutations, CTLA-4 and ICOS gene polymor-phisms in Turkish patients with common variable immunode-ficiency. J Clin Immunol 2012; 32(6): 1165‒79.

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

Giovannetti A, Pierdominici M, Mazzetta F, Marziali M, Renzi C, Mileo AM, et al. Unravelling the complexity of T cell abnor-malities in common variable immunodeficiency. J Immunol 2007; 178(6): 3932‒43.

Gregersen S, Aaløkken TM, Mynarek G, Kongerud J, Aukrust P, Frøland SS, et al. High resolution computed tomography and pulmonary function in common variable immunodeficiency. Respir Med 2009; 103(6): 873‒80.

Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood 2012; 119(7): 1650‒7.

Quinti I, Soresina A, Spadaro G, Martino S, Donnanno S, Agostini C, et al. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol 2007; 27(3): 308‒16.

O'Shea JJ, Ma A, Lipsky P. Cytokines and autoimmunity. Nat Rev Immunol 2002; 2(1): 37‒45.

Schreiber JR. Role of Toll like receptors in the antibody re-sponse to encapsulated bacteria. Front Biosci (Elite Ed) 2012; 4: 2638‒46.

Saussine A, Tazi A, Feuillet S, Rybojad M, Juillard C, Bergeron A, et al. Active chronic sarcoidosis is characterized by increased transitional blood B cells, increased IL-10-producing regulato-ry B cells and high BAFF levels. PLoS ONE 2012; 7(8): e43588.

Alexandrakis MG, Roussou P, Pappa CA, Messaritakis I, Xekalou A, Goulidaki N, et al. Relationship between circulating BAFF serum levels with proliferating markers in patients with mul-tiple myeloma. Biomed Res Int 2013; 2013: 389579.

Saulep-Easton D, Vincent FB, Quah PS, Wei A, Ting SB, Croce CM, et al. The BAFF receptor TACI controls IL-10 produc-tion by regulatory B cells and CLL B cells. Leukemia 2016; 30(1): 163‒72.

Rezaei N, Aghamohammadi A, Kardar GA, Nourizadeh M, Pourpak Z. T- helper 1 and 2 cytokine assay in patients with common variable immunodeficiency. J Investig Allergol Clin Immunol 2008; 18(6): 449‒53.

Kasztalska K, Ciebiada M, Cebula-Obrzut B, Górski P. Intra-venous immunoglobulin replacement therapy in the treatment of patients with common variable immunodeficiency disease: An open-label prospective study. Clin Drug Investig 2011; 31(5): 299‒307.

Barsotti NS, Almeida RR, Costa PR, Barros MT, Kalil J, Kokron CM. IL-10-Producing Regulatory B Cells Are Decreased in Patients with Common Variable Immunodeficiency. PLoS ONE 2016; 11(3): e0151761.

Zhou Z, Huang R, Danon M, Mayer L, Cunningham-Rundles C. IL-10 production in common variable immunodeficiency. Clin Immunol Immunopathol 1998; 86(3): 298‒304.

Holm AM, Aukrust P, Aandahl EM, Müller F, Taskén K, Frøland SS. Impaired secretion of IL-10 by T cells from patients with common variable immunodeficiency: Involvement of protein kinase A type I. J Immunol 2003; 170(11): 5772‒7.

Schmidt NW, Thieu VT, Mann BA, Ahyi AN, Kaplan MH. Bru-ton's tyrosine kinase is required for TLR-induced IL-10 pro-duction. J Immunol 2006; 177(10): 7203‒10.

Barbosa RR, Silva SP, Silva SL, Tendeiro R, Melo AC, Pedro E, et al. Monocyte activation is a feature of common variable im-munodeficiency irrespective of plasma lipopolysaccharide le-vels. Clin Exp Immunol 2012; 169(3): 263‒72.

Rezaei N, Aghamohammadi A, Mahmoudi M, Shakiba Y, Kardar GA, Mahmoudi M, et al. Association of IL-4 and IL-10 gene promoter polymorphisms with common variable immunodefi-ciency. Immunobiology 2010; 215(1): 81‒7.

Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regu-lation and functions of the IL-10 family of cytokines in in-flammation and disease. Annu Rev Immunol 2011; 29: 71‒109.

Rezaei N, Aghamohammadi A, Nourizadeh M, Kardar GA, Pourpak Z, Zare A, et al. Cytokine production by activated T cells in common variable immunodeficiency. J Investig Allergol Clin Immunol 2010; 20(3): 244‒51.

Eisenstein EM, Chua K, Strober W. B cell differentiation defects in common variable immunodeficiency are ameliorated after stimulation with anti-CD40 antibody and IL-10. J Immunol 1994; 152(12): 5957‒68.

Objavljeno
2021/01/26
Broj časopisa
Vol. 76 Br. 1 (2019): Vol. 76 Br. 1 (2019): Vojnosanit Pregl 2019; January Vol. 76 (No. 1)
Rubrika
Originalni članak