Clinical review for general practice

Common variable immunodeficiency (CVID) belongs to the group of primary immunodeficiencies with a predominant deficiency in antibody synthesis and the most common diagnosis among clinically significant cases of primary immunodeficiency in adults. The main laboratory criterion for this disease is considered to be hypogammaglobulinemia (a decrease in the level of IgG less than 4.5 g/l with a decrease in the level of IgA, with/without a decrease in the level of IgM). Clinical manifestations of CVID are diverse: infectious syndrome (chronic infections of the lower respiratory tract, sinusitis, otitis, infectious diarrhea, septic arthritis), autoimmune syndrome (cytopenias, systemic rheumatic diseases), non-infectious pathology of the gastrointestinal tract (celiac-like or IBD-like syndromes , nodular hyperplasia of the mucosa), interstitial lung diseases, pathological non-malignant lymphoproliferation (lymphadenopathy, hepatosplenomegaly), oncological diseases, the formation of non-caseating granulomas in the internal organs). Due to the lack of a typical clinical picture, the diagnosis of CVID in adults is often made many years late, especially if the clinical picture is dominated by non-infectious manifestations. The article presents a clinical case when the patient had recurrent lymphadenopathy as the main symptom for several years. After examination by various specialists, she was referred to an immunologist because hypoproteinemia and a sharp decrease in the gamma fraction of globulins have been revealed. An immunological study revealed agammaglobulinemia and a pronounced imbalance of T-lymphocyte subpopulations (a significant decrease in the number of CD4+ cells and an increase in CD8+ cells). The clinical significance of T-lymphocyte disorders in CVID, the need for treatment with adequate doses of intravenous immunoglobulins are discussed. 

1. Seidel MG, Kindle G, Gathmann B 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.
2. Щербина А.Ю., Кузьменко Н.Б. Классификация первичных иммунодефицитов как отражение современных представлений об их патогенезе и терапевтических подходах. 2017; 3: 51–57.
[Shherbina AJu, Kuz'menko NB. Klassifikacija pervichnyh immunodeficitov kak otrazhenie sovremennyh predstavlenij ob ih patogeneze i terapevticheskih podhodah. 2017; 3: 51–7 (in Russian).]
3. Gupta A Primary Immunodeficiency Disorders: Where Do We Stand? Indian J Pediatr 2019; 86 (10): 873–4.
4. Васильева М.М., Сай И.А. Первичные иммунодефициты с преимущественным нарушением синтеза антител. Здравоохранение Дальнего Востока. 2021; 4: 24–32.
[Vasil'eva M.M., Saj I.A. Pervichnye immunodeficity s preimushhestvennym narusheniem sinteza antitel. Zdravoohranenie Dal'nego Vostoka. 2021; 4: 24–32 (in Russian).]
5. Ягудина Л.А., Хакимова Д.М. Общая вариабельная иммунная недостаточность в клинической практике. Казанский медицинский журнал. 2015; 96 (2): 249–52.
[Jagudina L.A., Hakimova D.M. Obshhaja variabel'naja immunnaja nedostatochnost' v klinicheskoj praktike. Kazanskij medicinskij zhurnal. 2015; 96 (2): 249–52 (in Russian).]
6. Белевцев М.В., Шитикова М.Г., Гурьянова И.Е. и др. Иммунологические и генетические особенности общей вариабельной иммунной недостаточности у детей и взрослых в Республике Беларусь. Медико-биологические проблемы жизнедеятельности. 2019; 1 (21): 104–11.
[Belevcev M.V., Shitikova M.G., Gur'janova I.E. et al. Immunologicheskie i geneticheskie osobennosti obshhej variabel'noj imunnoj nedostatochnosti u detej i v roslyh v Respublike Belarus'. Mediko-biologicheskie problemy zhiznedejatel'nosti; 2019; 1 (21): 104–11 (in Russian).]
7. Yazdani R, Habibi S, Sharifi S et al. Common variable immunodeficiency: epidemiology, pathogenesis, clinical manifestations, diagnosis, classification and management. J Investig Allergol Clin Immunol 2020; 30 (1): 14–34.
8. Mouillot G, Carmagnat M, Gerard L et al. В-сеll and T-cell phenotypes in CVID patients correlate with clinical phenotype of the disease. J Clin Immunol 2010; 30 (5): 746–55.
9. Azizi G, Rezaei N, Kiaee F et al. T-cell abnormalities in common variable immune deficiency. J Investig Allergol Clin Immunol 2016; 26 (4): 233–42.
10. Sakia B, Gupta S. Common variable immunodeficiency. Indian J Pediatr 2016; 83 (4): 338–44.
11. Fernando SL, Jang HS-I, Li J. The immune dysregulation of common variable immunodeficiency disorders. Immunol Lett 2021; 230: 21–6.
12. Караулов А.В., Сидоренко И.В., Капустина А.С. Совершенствование верификации и тактики ведения первичного иммунодефицита –
общей вариабельной иммунной недостаточности у взрослых. Иммунопатология, аллергология, инфектология. 2011; 3: 32–41.
[Karaulov A.V., Sidorenko I.V., Kapustina A.S. Sovershenstvovanie verifikacii i taktiki vedenija pervichnogo immunodeficita – obshhej variabel'noj immunnoj nedostatochnosti u vzroslyh. Immunopatologija, allergologija, infektologija. 2011; 3: 32–41 (in Russian).]
13. Sanchez LA, Maggadottir SM, Pantell MS et al. Two sides of the same coin: pediatric-onset and adult-onset common variable immune deficiency. J Clin Immunol 2017; 37 (6): 592–602.
14. Giovanetti A, Pierdominici M, Mazetta F et al. Unravelling the complexity of T-cell abnormalities in common variable immunodeficiency. J Immunol 2007; 178 (6): 3932–43.
15. Шабашова Н.В., Филиппова И.В., Учеваткина А.Е., Фролова Е.В. ОВИН у взрослых. Терапевтический архив. 2016; 82 (11): 94–8.
[Shabashova N.V., Filippova I.V., Uchevatkina A.E., Frolova E.V. OVIN u vzroslyh. Ter. Arkh. 2016; 82 (11): 94–8 (in Russian).]
16. Bertinchamp R, Gerard L, Boutboul D et al. Exclusion of patients with severe N-cell defect improves the definition of common variable immunodeficiency. J Allergy Immunol Pract 2016; 4 (6): 1147–57.
17. Donq J, Liaq H, Wen D, Wanq J. Adult common immunodeficiency. Am J Med Sci 2016; 351 (3): 239–43.