Importance of cellular immunity link for efficiency of replacement therapy in common variable immune deficiency

Abstract

Lifetime use of IgG replacement therapy is the standard of CVID treatment. However, full control over stabilization of chronic infection loci is not always achieved, even if this therapy is continuously applied. The purpose of this study was to carry out comparative analysis of changes in cellular component of adaptive and innate immune response, depending on effectiveness of replacement therapy of patients with infectious CVID phenotype. The observation group consisted of 15 patients with CVID who were diagnosed since early childhood in 100% of cases. They had prolonged respiratory infections followed by the development of complications requiring continuous treatment with antibiotics.After reaching mean age of 15 years old, the intensity of infection-associated antibody deficiency was 6-8 times per year. After verification of the diagnosis, the patients received replacement therapy, first at the saturation dose, and, after stabilization of IgG at the level of 7-8 g/l, at the monthly maintenance dose. The clinical course of the disease was traced during a full year of replacement therapy, and the cellular immunity indices were evaluated. In all patients, after a year of therapy corresponding to clinical guidelines, there was an improvement in quality of life indices, decreased rates of recurrent bacterial infections. At the same time, 40% of them continued to suffer, on average, 5.4±1.1 times a year and required long-term courses of antibiotic therapy. Evaluation of immune status did not reveal statistically significant differences in IgG plasma saturation between the groups of patients with different treatment efficiency: 8.7 (8-9) g/l and 9.1 (8.5-10.5) g/l, at p = 0.5. The differences related to immune cell factors in cases of smaller effect of IVIG therapy are manifested in higher relative numbers of T effectors containing lytic Granzyme B granules and CD14+CD284+ monocytes, accompanied by lower spontaneous active oxygen forms produced by neutrophils, lesser contents of CD16+ natural killers in peripheral blood.The obtained data illustrate the value of monitoring, not only serum IgG level, but also the parameters of the cellular immune response. Such analysis may be essential as a prognostic criterion for efficacy of IVIG therapy. Reduced levels of some parameters of innate immunity cells serves a basis to formulate the concept of combined treatment and usage of tools that alter functions of immunocompetent cells.

Keywords

• cvid
• ivig replacement therapy
• cellular immunity