Features of the immunoreactivity T and B lymphocytes subpopulations and cytokine imbalance in patients with hepatosplenomegaly of different etiology

Abstract

The aim was to study the mechanisms of immunological dysregulation of cytokine and immunoglobulin production, changes in the CD expression of T and B lymphocyte subpopulations in patients with hepatosplenomegaly of different etiology. Materials and methods. We examined 73 patients with liver cirrhosis complicated by portal hypertension, hepatosplenomegaly, and bleeding from phlebectasia. We identified three groups of patients depending on the triggering factors of cirrhosis: the first (I) group – HBV/HCV; the second (II) group – CMV/VEB; the third (III) group – hereditary enzymopathies. The study material was lymphocytes and blood serum. We used the methods of ELISA, immunofluorescence and flow cytometry. Results. An increase in the concentration of IgA and IgM was revealed against the background of normal number of CD22+ B lymphocytes with HBV/HCV (I group), high level of IgM and their producers, B lymphocytes, with CMV/VEB (II group), in group III with hereditary enzymopathies, the concentration of all immunoglobulins was normal with an increased content of B lymphocytes. Multidirectional changes in the content of cytokines were revealed: in group I the synthesis of anti-inflammatory cytokines IL-4, IL-10 and in group II – pro-inflammatory IL-1β, INF-γ, TNF-α dominated; in group III the concentration of IL-6 and vascular growth factor (VEGF) was maximally increased. The number of activated CD3+CD4+CD25+ T cells was reduced in groups I and II – by 2.3 and 2.0 times respectively, in group III – increased by 1.2 times. The number of regulatory T lymphocytes CD3+CD4+CD25+CD127neg was reduced by half in I and II groups. Expression of co-stimulatory molecules CD3+CD4+CD28+ was low in all groups and the maximum decrease was in group III. In patients with HCV/HBV, an increase in the expression of the late activation marker of lymphocytes CD3+HLA-DR+ by an average of 63 % was noted. Conclusions. The revealed immune disorders in hepatosplenomegaly of different etiology are characterized by multidirectional changes. Approaches to the treatment of these patients should be complex, taking into account the trigger factors that cause dysregulation of immune responses, which leads to further destruction, and focuses at remodeling target organs.

Perspective Chapter: Specific predictors of the autoimmune reactions formation in case of immunocompetent organs damage in patients with myasthenia gravis and hepatosplenomegaly

“…In group I, a maximum twofold increase in the serum concentration of IgA was revealed, as a strong opsonizer and participant in the antigen-antibody-complement complex. This was probably due to the entry of large amounts of IgA contained in the intestinal mucosa through portosystemic anastomoses directly into the bloodstream during abdominal infection [68].…”