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  • Author: D. Kyurkchiev x
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E. Krasimirova and D. Kyurkchiev

Abstract

Systemic sclerosis (SSc) is a chronic progressive autoimmune disease characterized by skin and multiorgan involvement with alterations in both the innate and adaptive immunities. The hallmark of the disease is widespread fibrosis engaging the skin and multiple internal organs, as well as the musculoskeletal system. There is mounting evidence that T cells are key players in the pathogenesis of scleroderma. The current review discusses the role of the different T helper (Th) lymphocyte subsets in the processes of inflammation and fibrosis, characteristics for the pathogenesis of the disease. Cytokines produced by Th cell populations have a major effect on endothelial cells and fibroblasts in the context of favoring/inhibiting the vasculopathy and the fibrosis spread. The Th2 pro-fibrotic cytokines IL-4 and IL-13 have been shown to induce collagen synthesis by fibroblasts, whereas IFN-γ demonstrates an inhibitory effect. Increased Th17 cells are present in the scleroderma skin infiltrates. The combination of IL-17, IFN-γ and TGF-β levels in CD45RO and CD45RA cells from patients with SSc is useful to distinguish between the limited and the diffuse phenotype of the disease. There are accumulating data for functional and numerical alterations in the Tregs in SSc. High levels of TNF-α which might reduce the suppressive ability of Tregs have been described. According to some studies, the number of Tregs in scleroderma skin biopsies has been decreased against the normal absolute number of Tregs in peripheral blood of the same patients, which suggests suppressed immunomodulatory response. Other studies reported increased frequency of Tregs in peripheral blood of patients with systemic sclerosis and established a correlation with disease activity. The main immunological challenge remains the identification of the trigger of the autoimmune response in SSc, the causes for preferential Th2-type cell responses and the immunological differences between the diffuse and the limited cutaneous form of the disease.

Open access

Tsvetelina Velikova, R. Miladinova, E. Ivanova-Todorova, D. Kyurkchiev and Z. Spasova

Abstract

Crohn's disease (CD) may have some severe complications that pose an increasing health burden and negatively impact the quality of life. There are two major types - intestinal and extraintestinal complications, in which immune and non-immune mechanisms take place. We aimed to search for some associations between specific extraintestinal manifestation and intestinal complications in CD patients with some clinicallaboratory findings, immunological markers, and the therapy administered. We examined retrospectively medical files of 26 patients with CD at mean age 42 ± 13 years, including the laboratory results. The immunological markers fecal calprotectin (FC) and fecal lactoferrin (FL) were assessed in frozen fecal samples of the chosen patients. Seventy-three percent of the investigated CD patients had some extraintestinal manifestation and/or intestinal complications, at least 13/26 had intestinal complications. All three patients with extraintestinal signs were positive for FC and 2/3 were positive for FL. We observed a higher serum level of CRP (24.49 mg/l vs. 3.13 mg/l, p = 0.010), slightly lowered serum level of hemoglobin (120 g/l vs. 145 g/l, p = 0.044) and about 2-fold lower iron level (7.23 μmol/l vs. 14.0 μmol/l, p = 0.019) in patients with intestinal complications compared to patients without complications, respectively. Four out of thirteen patients with intestinal complications were without immunosuppressive therapy at the time of our study, and nine out of thirteen - on immunosuppressive drugs. Routine laboratory and immunology testing could be beneficial for gastroenterologists in identifying patients at high risk for the development of complications and in the decision making for more aggressive therapy early after diagnosis.