Functional status of blood neutrophils in congenital defects of antibody production

Abstract

We evaluated some functional indices of neutrophils in 100 adult patients with a verified diagnosis of primary antibody production deficiency (44 patients with common variable immunodeficiency – CVID, and 56 patients with selective IgA deficiency – SigAD). The diagnosis was made according to the criteria of the Pan-American Group for Immunodeficiency and European Society for Immunodeficiency. The criteria for diagnosis were based on clinical data, medical history and results of laboratory tests. All patients with CVID received regular immunoglobulin replacement therapy, and the SIgAD patients received symptomatic treatment on demand. The examination was performed beyond the infectious episodes, inflammatory events or exacerbation of chronic disorders upon admission for planned hospitalisation, before any therapeutic and diagnostic procedures. In addition to standard clinical and laboratory examination appointed for the mentioned diseases, we assessed fnctional status of neutrophils: superoxide-anion radical production, NETosis, phagocytosis and apoptosis. Taking into account clinical manifestations, the patients with CVID were divided into 6 clinical subgroups: without CVID-related complications (13.6%); with infectious complications, i.e., bronchiectatic disease (15.9%), autoimmune syndromes (22.7%), polyclonal lymphoid infiltration (13.6%), enteropathic syndrome (34.1%), and malignant neoplasms (9.1%). Four phenotypes were identified in the patients with SIgAD: absence of SIgAD-related complications (28.6%); autoimmune syndrome (16.1%), non-malignant lymphoproliferation (3.6%) and enteropathy (28.6%). Higher incidence of non-infectious complications (autoimmune syndrome, non-malignant lymphoproliferation, enteropathies) was found in СVID compared to SIgAD patients (χ2 = 10.27; p = 0.001). Patients from the both groups showed changes in neutrophil reactivity compared to control values expressing higher basal generation of superoxide radicals (p < 0.001), NETosis activity (p = 0.005) and apoptosis (p < 0.001) with decreased phagocytic function (p < 0.001) and lower reserve for reactive oxygen species formation (p < 0.001). The maximal degree of changes in phagocytosis and superoxide-producing activity was observed in СVID; altered NETosis was revealed in SIgAD. The development of non-infectious complications was accompanied by a significant increase in stimulated NETosis indexes, thus suggesting a promising index in order to assess stability of clinical course and to predict development of complications in congenital defects of antibody production.

Keywords

• selective iga deficiency
• common variable immunodeficiency
• adult patients
• clinical phenotypes
• neutrophils
• netosis