Clinical and immunological features of 44 common variable immunodeficiency patients: the experience of a single center in Turkey
Main Article Content
Keywords
Common variable immunodeficiency, Hypogammaglobulinemia, Immunoglobulin therapy
Abstract
Introduction and objectives: Common variable immunodeficiency (CVID) is one of the most prevalent forms of primary immunodeficiency characterized by hypogammaglobinemia. Its heterogeneous clinical features include recurrent respiratory tract infections and other complications such as gastrointestinal, autoimmunity, and lymphoproliferative disorders. The aim of this article is to evaluate the general characteristics of CVID patients.
Materials and methods: Clinical and immunological features of 44 CVID patients were evaluated retrospectively with long-term follow-up. Patients who participated in the study were diagnosed according to the criteria of the European Society for Immunodeficiency Diseases (ESID).
Results: The median age at onset of symptoms was 2.75 years (range 6 months to 17 years), and the median age at diagnosis was 7.75 years (range 4---20 years). The average delay in diagnosis was 4.6 years (range 1---14 years). Positive family history was 18.2%. Before treatment, patients’ median total serum IgG was 271.5 mg/dL, median IgA was 7.5 mg/dL, and median IgM was 21 mg/dL. Infections were the most common clinical manifestation, and 63.6% of patients presented with sinopulmonary infection as the first manifestation. Bronchiectasis developed in 23 CVID subjects, while bronchiectasis was detected prior to CVID diagnosis in eight patients. All patients received immunoglobulin replacement therapy, and one patient died because of granulomatous lymphocytic interstitial lung disease (GLILD).
Conclusions: CVID is a heterogeneous group of immunologic disorders with unknown etiology. There are significant differences in the clinical presentation and prevalence of CVID-related complications among countries. Local guidelines for diagnosis and clinical follow-up are needed.
References
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28. Ogershok PR, Hogan MB, Welch JE, Corder WT, Wilson NW. Spectrum of illness in pediatric common variable immunodeficiency. Ann Allergy Asthma Immunol. 2006;97:653---6, http://dx.doi.org/10.1016/S1081-1206(10)61096-4.
29. Gangemi S, Allegra A, Musolino C. Lymphoproliferative disease and cancer among patients with common variable immunodeficiency. Leuk Res. 2015;39:389---96, http://dx.doi.org/10.1016/j.leukres.2015.02.002.
30. Ardeniz O, Bas¸o˘glu OK, Güns¸ar F, Unsel M, Bayraktaro˘glu S, Mete N, et al. Clinical and immunological analysis of 23 adult patients with common variable immunodeficiency. J Investig Allergol Clin Immunol. 2010;20:222---36.
31. Busse PJ, Razvi S, Cunningham-Rundles C. Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency. J Allergy Clin Immunol. 2002;109:1001---4, http://dx.doi.org/10.1067/mai.2002.124999.
32. Jolles S, Orange JS, Gardulf A, Stein MR, Shapiro R, Borte M, et al. Current treatment options with immunoglobulin G for the individualization of care in patients with primary immunodeficiency disease. Clin Exp Immunol. 2015;179:146---60, http://dx.doi.org/10.1111/cei.12485.
33. Abolhassani H, Sadaghiani MS, Aghamohammadi A, Ochs HD, Rezaei N. Home-based subcutaneous immunoglobulin versus hospital-based intravenous immunoglobulin in treatment of primary antibody deficiencies: systematic review and meta analysis. J Clin Immunol. 2012;32:1180---92, http://dx.doi.org/10.1007/s10875-012-9720-1.
34. Chua I, Quinti I, Grimbacher B. Lymphoma in common variable immunodeficiency: interplay between immune dysregulation, infection and genetics. Curr Opin Hematol. 2008;15:368---74, http://dx.doi.org/10.1097/MOH.0b013e328302c7b6.
35. Piquer Gibert M, Alsina L, Giner Munoz ˜ MT, Cruz Martínez O, Ruiz Echevarria K, Dominguez O, et al. Non-Hodgkin lymphoma in pediatric patients with common variable immunodeficiency. Eur J Pediatr. 2015;174:1069---76, http://dx.doi.org/10.1007/s00431-015-2508-6.
2. Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119:1650---7, http://dx.doi.org/10.1182/blood-2011-09-377945.
3. Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, CunninghamRundles C, de la Morena MT, et al. International Consensus Document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4:38---59, http://dx.doi.org/10.1016/j.jaip.2015.07.025.
4. Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies, Representing PAGID (PanAmerican Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999;93:190---7, http://dx.doi.org/10.1006/clim.1999.4799.
5. European Society for Immunodeficiencies. New Clinical Diagnosis Criteria for the ESID Registry; 2020. https://esid.org/Working-Parties/Registry/Diagnosis-criteria
6. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34---48, http://dx.doi.org/10.1006/clim.1999.4725.
7. Gathmann B, Mahlaoui N, CEREDIH, Gérard L, Oksenhendler E, Warnatz K, Schulze I, et al. Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol. 2014;134:116---26, http://dx.doi.org/10.1016/j.jaci.2013.12.1077.
8. Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136:1186---205, http://dx.doi.org/10.1016/j.jaci.2015.04.049.
9. Aksu G, Genel F, Koturo˘glu G, Kurugöl Z, Kütükc¸üler N. Serum immunoglobulin (IgG, IgM, IgA) and IgG subclass concentrations in healthy children: a study using nephelometric technique. Turk J Pediatr. 2006;48:19---24.
10. Ikincio˘gullari A, Kendirli T, Do˘gu F, E˘gin Y, Reisli I, Cin S, et al. Peripheral blood lymphocyte subsets in healthy Turkish children. Turk J Pediatr. 2004;46:125---30.
11. Kilic SS, Ozel M, Hafizoglu D, Karaca NE, Aksu G, Kutukculer N. The prevalences [correction] and patient characteristics of primary immunodeficiency diseases in Turkey--- two centers study. J Clin Immunol. 2013;33:74---83, http://dx.doi.org/10.1007/s10875-012-9763-3.
12. Karaca NE, Severcan EU, Bilgin BG, Azarsiz E, Akarcan S, Gunaydın NC, et al. Familial inheritance and screening of first-degree relatives in common variable immunodeficiency and immunoglobulin A deficiency patients. Int J Immunopathol Pharmacol. 2018;32, http://dx.doi.org/10.1177/2058738418779458.
13. Alkan G, Keles S, Reisli ˙I. Evaluation of clinical and immunological characteristics of children with common variable immunodeficiency. Int J Pediatr. 2018:3527480, http://dx.doi.org/10.1155/2018/3527480.
14. Erdem SB, Gulez N, Genel F, Karaman S, Nacaroglu HT. Characteristics of the patients followed with the diagnosis of common variable immunodeficiency and the complications. Cent Eur J Immunol. 2019;44:119---26, http://dx.doi.org/10.5114/ceji.2019.87060.
15. Lin LJ, Wang YC, Liu XM. Clinical and immunological features of common variable immunodeficiency in China. Chin Med J. 2015;128:310---5, http://dx.doi.org/10.4103/0366-6999.150092.
16. Aghamohammadi A, Farhoudi A, Moin M, Rezaei N, Kouhi A, Pourpak Z, et al. Clinical and immunological features of 65 Iranian patients with common variable immunodeficiency. Clin Diagn Lab Immunol. 2005;12:825---32, http://dx.doi.org/10.1128/CDLI.12.7.825-832.2005.
17. Karakoc-Aydiner E, Ozen AO, Baris S, Ercan H, Ozdemir C, Barlan I. Alteration in humoral immunity is common among family members of patients with common variable immunodeficiency. J Investig Allergol Clin Immunol. 2014;24:346---51.
18. 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;27:308---16, http://dx.doi.org/10.1007/s10875-007-9075-1.
19. Ramírez-Vargas N, Arablin-Oropeza SE, Mojica-Martínez D, Yamazaki-Nakashimada MA, de la Luz García-Cruz M, Terán-Juárez LM, et al. Clinical and immunological features of common variable immunodeficiency in Mexican patients. Allergol Immunopathol (Madr). 2014;42:235---40, http://dx.doi.org/10.1016/j.aller.2013.01.007.
20. Mohammadinejad P, Aghamohammadi A, Abolhassani H, Sadaghiani MS, Abdollahzade S, Sadeghi B, et al. Pediatric patients with common variable immunodeficiency: long-term follow-up. J Investig Allergol Clin Immunol. 2012;22:208---14.
21. Aydogan M, Eifan AO, Gocmen I, Ozdemir C, Bahceciler NN, Barlan IB. Clinical and immunologic features of pediatric patients with common variable immunodeficiency and respiratory complications. J Investig Allergol Clin Immunol. 2008;18:260---5.
22. Rivoisy C, Gérard L, Boutboul D, Malphettes M, Fieschi C, Durieu I, et al. Parental consanguinity is associated with a severe phenotype in common variable immunodeficiency. J Clin Immunol. 2012;32:98---105, http://dx.doi.org/10.1007/s10875-011-9604-9.
23. Shah JL, Amin SB, Verma N, Mohammed TL. Granulomatous-lymphocytic interstitial lung disease in a patient with common variable immunodeficiency. Curr Probl Diagn Radiol. 2018;47:282---4, http://dx.doi.org/10.1067/j.cpradiol.2017.04.007.
24. Bates CA, Ellison MC, Lynch DA, Cool CD, Brown KK, Routes JM. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol. 2004;114:415---21, http://dx.doi.org/10.1016/j.jaci.2004.05.057.
25. Agarwal S, Cunningham-Rundles C. Autoimmunity in common variable immunodeficiency. Curr Allergy Asthma Rep. 2009;9:347---52, http://dx.doi.org/10.1007/s11882-009-0051-0.
26. Wang J, Cunningham-Rundles C. Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID). J Autoimmun. 2005;25:57---62, http://dx.doi.org/10.1016/j.jaut.2005.04.006.
27. Pituch-Noworolska A, Siedlar M, Kowalczyk D, Szaflarska A, Błaut-Szlósarczyk A, Zwonarz K. Thrombocytopenia in common variable immunodeficiency patients --- clinical course, management, and effect of immunoglobulins. Cent Eur J Immunol. 2015;40:83---90, http://dx.doi.org/10.5114/ceji.2015.50838.
28. Ogershok PR, Hogan MB, Welch JE, Corder WT, Wilson NW. Spectrum of illness in pediatric common variable immunodeficiency. Ann Allergy Asthma Immunol. 2006;97:653---6, http://dx.doi.org/10.1016/S1081-1206(10)61096-4.
29. Gangemi S, Allegra A, Musolino C. Lymphoproliferative disease and cancer among patients with common variable immunodeficiency. Leuk Res. 2015;39:389---96, http://dx.doi.org/10.1016/j.leukres.2015.02.002.
30. Ardeniz O, Bas¸o˘glu OK, Güns¸ar F, Unsel M, Bayraktaro˘glu S, Mete N, et al. Clinical and immunological analysis of 23 adult patients with common variable immunodeficiency. J Investig Allergol Clin Immunol. 2010;20:222---36.
31. Busse PJ, Razvi S, Cunningham-Rundles C. Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency. J Allergy Clin Immunol. 2002;109:1001---4, http://dx.doi.org/10.1067/mai.2002.124999.
32. Jolles S, Orange JS, Gardulf A, Stein MR, Shapiro R, Borte M, et al. Current treatment options with immunoglobulin G for the individualization of care in patients with primary immunodeficiency disease. Clin Exp Immunol. 2015;179:146---60, http://dx.doi.org/10.1111/cei.12485.
33. Abolhassani H, Sadaghiani MS, Aghamohammadi A, Ochs HD, Rezaei N. Home-based subcutaneous immunoglobulin versus hospital-based intravenous immunoglobulin in treatment of primary antibody deficiencies: systematic review and meta analysis. J Clin Immunol. 2012;32:1180---92, http://dx.doi.org/10.1007/s10875-012-9720-1.
34. Chua I, Quinti I, Grimbacher B. Lymphoma in common variable immunodeficiency: interplay between immune dysregulation, infection and genetics. Curr Opin Hematol. 2008;15:368---74, http://dx.doi.org/10.1097/MOH.0b013e328302c7b6.
35. Piquer Gibert M, Alsina L, Giner Munoz ˜ MT, Cruz Martínez O, Ruiz Echevarria K, Dominguez O, et al. Non-Hodgkin lymphoma in pediatric patients with common variable immunodeficiency. Eur J Pediatr. 2015;174:1069---76, http://dx.doi.org/10.1007/s00431-015-2508-6.
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Dec 15, 2020
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Nepesov, S., Aygun, F., Firtina, S., Cokugras, H., & Camcioglu, Y. (2020). Clinical and immunological features of 44 common variable immunodeficiency patients: the experience of a single center in Turkey. Allergologia Et Immunopathologia, 48(6), 675-685. https://all-imm.com/index.php/aei/article/view/106
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How to Cite
Nepesov, S., Aygun, F., Firtina, S., Cokugras, H., & Camcioglu, Y. (2020). Clinical and immunological features of 44 common variable immunodeficiency patients: the experience of a single center in Turkey. Allergologia Et Immunopathologia, 48(6), 675-685. https://all-imm.com/index.php/aei/article/view/106