The relationship between neutropenia and disease prognosis in patients with Common Variable Immunodeficiency (CVID)
Main Article Content
Keywords
common variable immunodeficiency, neutropenia, autoimmune cytopenia, primary immunodeficiency, survival analysis
Abstract
Objective: This study aimed to determine the frequency of neutropenia in patients with common variable immunodeficiency (CVID) and investigate its relationship with disease prognosis.
Methods: Data from 84 patients diagnosed with CVID and followed between 2019 and 2024 at the Department of Adult Clinical Immunology and Allergy, Necmettin Erbakan University, were retrospectively reviewed. Patients were divided into two groups based on the presence or absence of neutropenia. Demographic data, clinical findings, laboratory parameters, and survival rates were compared. Statistical analyses included the Mann–Whitney U test, the Chi-square test, and the Kaplan–Meier survival analysis.
Results: A total of 84 patients diagnosed with CVID were included in the study, with a median age of 38 years (range, 20–79 years). Of the participants, 48.8% were females (n = 41). Neutropenia was observed in 28.5% of patients (n = 24). The most common presenting complaints included autoimmune cytopenias, such as anemia and thrombocytopenia. Compared to non-neutropenic patients (n = 60), those with neutropenic CVID had a significantly higher mortality rate (33.3% vs 6.7%, P = 0.004). According to Kaplan–Meier survival analysis, the 8-year survival rates were 57.5 and 92.5% for neutropenic and for non-neutropenic CVID patients (p < 0.001), respectively.
Conclusion: This study suggests that neutropenia in CVID patients may be more than just a hematological issue; it could also serve as an important clinical marker associated with increased mortality. Recognizing and closely monitoring neutropenia is essential for effective CVID management.
References
2 Ameratunga R, Jordan A, Cavadino A, Ameratunga S, Hills T, Steele R, et al. Bronchiectasis is associated with delayed diagnosis and adverse outcomes in the New Zealand Common Variable Immunodeficiency Disorders cohort study. Clin Exp Immunol. 2021;204(3):352–60. 10.1111/cei.13595
3 Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, et al. The EUROclass trial: Defining subgroups in common variable immunodeficiency. Blood. 2008;111(1):77–85. 10.1182/blood-2007-06-091744
4 Boileau J, Mouillot G, Gérard L, Carmagnat M, Rabian C, Oksenhendler E, et al. Autoimmunity in common variable immunodeficiency: Correlation with lymphocyte phenotype in the French DEFI study. J Autoimmun. 2011;36(1):25–32. 10.1016/j.jaut.2010.10.002
5 Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, et al. The European Society for Immunodeficiencies (ESID) registry working definitions for the clinical diagnosis of inborn errors of immunity. J Allergy Clin Immunol Pract. 2019;7(6):1763–70. 10.1016/j.jaip.2019.02.004
6 Cham B, Bonilla MA, Winkelstein J. Neutropenia associated with primary immunodeficiency syndromes. Seminars Hematol. 2002;39(2):107–12. 10.1053/shem.2002.31916
7 Feuille EJ, Anooshiravani N, Sullivan KE, Fuleihan RL, Cunningham-Rundles C. Autoimmune cytopenias and associated conditions in CVID: A report from the USIDNET Registry. J Clin Immunol. 2018;38(1):28–34. 10.1007/s10875-017-0456-9
8 Lemos S, Jacob CM, Pastorino AC, Castro APB, Fomin ÂB, Carneiro-Sampaio MM. Neutropenia in antibody-deficient patients under IVIG replacement therapy. Pediatr Allergy Immunol. 2009;20(1):97–101. 10.1111/j.1399-3038.2008.00741.x
9 Paquin-Proulx D, Sandberg JK. Persistent immune activation in CVID and the role of IVIg in its suppression. Front Immunol. 2014;5:637. 10.3389/fimmu.2014.00637
10 Lopes-da-Silva S, Rizzo LV. Autoimmunity in common variable immunodeficiency. J Clin Immunol. 2008;28:46–55.
11 Odnoletkova I, Kindle G, Quinti I, Grimbacher B, Knerr V, Gathmann B, et al. The burden of common variable immunodeficiency disorders: A retrospective analysis of the European Society for Immunodeficiency (ESID) registry data. Orphanet J Rare Dis. 2018;13(1):201. 10.1186/s13023-018-0941-0
12 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. 10.1182/blood-2011-09-377945
13 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. 10.1007/s10875-007-9075-1
14 Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: Clinical and immunological features of 248 patients. Clin Immunol (Orlando, Fla). 1999;92(1):34–48. 10.1006/clim.1999.4725
15 Guffroy A, Mourot-Cottet R, Gérard L, Gies V, Lagresle C, Pouliet A, et al. Neutropenia in patients with common variable immunodeficiency: A rare event associated with severe outcome. J Clin Immunol. 2017;37(7):715–6. 10.1007/s10875-017-0434-2
16 Berkovitch M, Dolinski G, Tauber T, Aladjem M, Kaplinsky C. Neutropenia as a complication of intravenous immunoglobulin (IVIG) therapy in children with immune thrombocytopenic purpura: Common and non-alarming. Int J Immunopharmacol. 1999;21(6):411–5. 10.1016/s0192-0561(99)00020-x
17 Niebanck AE, Kwiatkowski JL, Raffini LJ. Neutropenia following IVIG therapy in pediatric patients with immune-mediated thrombocytopenia. J Pediatr Hematol Oncol. 2005;27(3):145–7. 10.1097/01.mph.0000155871.26380.84
18 Bride KL, Vincent T, Smith-Whitley K, Lambert MP, Bleesing JJ, Seif AE, et al. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: Results of a prospective multi-institutional trial. Blood. 2016;127(1):17–28. 10.1182/blood-2015-07-657981
19 Ghorbani M, Fekrvand S, Shahkarami S, Yazdani R, Sohani M, Shaghaghi M, et al. The evaluation of neutropenia in common variable immune deficiency patients. Expert Rev Clin Immunol. 2019;15(11):1225–33. 10.1080/1744666x.2020.1677154