Are cytotoxic effector cells changes in peripheral blood of patients with Sjögren's syndrome related to persistent virus infection: Suggestions and conundrums.

Etiology of Sjögren's syndrome (SS) is still unknown, but there is strong evidence that certain pathogens of bacterial or viral origin can incite autoimmune response. The aim of this study was to quantitatively evaluate changes of the main cell populations (dendritic cells, natural killer, natural killer T and cytotoxic T lymphocytes) presumably participating in virus clearance in peripheral blood of patients with primary SS (pSS). In analyzing cytotoxic T lymphocytes (CTL) populations we observed alterations in the frequency of highly cytotoxic effector CD8high/57+/27-/45RA+, less cytotoxic CD8high/57-/27-/45RA+ effector cells and cytotoxic memory CD8high/57+/27+/45RA- effector cells. We found a decrease of conventional dendritic cells (cDC) population in peripheral blood of pSS patients. It is possible that, a decrease of effector CTL and cDC, accompanied by increase of transitory phenotype memory CTL in peripheral blood of pSS patients may be associated with viral etiopathogenesis of Sjögren's syndrome.

Skeletal Muscle-Derived Stem/Progenitor Cells: A Potential Strategy for the Treatment of Acute Kidney Injury.

Skeletal muscle-derived stem/progenitor cells (MDSPCs) have been thoroughly investigated and already used in preclinical studies. However, therapeutic potential of MDSPCs isolated using preplate isolation technique for acute kidney injury (AKI) has not been evaluated. We aimed to characterize rat MDSPCs, compare them with bone marrow mesenchymal stem cells (BM-MSCs), and evaluate the feasibility of MDSPCs therapy for gentamicin-induced AKI in rats. We have isolated and characterized rat MDSPCs and BM-MSCs. Characteristics of rat BM-MSCs and MDSPCs were assessed by population doubling time, flow cytometry, immunofluorescence staining, RT-PCR, and multipotent differentiation capacity. Gentamicin-induced AKI model in rat was used to examine MDSPCs therapeutic effect. Physiological and histological kidney parameters were determined. MDSPCs exhibited similar immunophenotype, stem cell gene expression, and multilineage differentiation capacities as BM-MSCs, but they demonstrated higher proliferation rate. Single intravenous MDSPCs injection accelerated functional and morphological kidney recovery, as reflected by significantly lower serum creatinine levels, renal injury score, higher urinary creatinine, and GFR levels. PKH-26-labeled MDSPCs were identified within renal cortex 1 and 2 weeks after cell administration, indicating MDSPCs capacity to migrate and populate renal tissue. In conclusion, MDSPCs are capable of mediating functional and histological kidney recovery and can be considered as potential strategy for AKI treatment.

Distribution of Peripheral Lymphocyte Populations in Primary Sjögren's Syndrome Patients.

Purpose of this study was to evaluate the lymphocyte populations' distribution changes in peripheral blood of patients with primary Sjögren's syndrome (pSS). Lymphocyte populations' distribution changes in peripheral blood of pSS patients were investigated in 52 patients with pSS and in 28 healthy controls by flow cytometry. We found decreased absolute count of CD3(+) T cell population in pSS patients. Analysis of CD4(+) T cell population showed significant proportion and absolute count differences in pSS patient's blood with SSA/SSB antibodies (Abs) in comparison to controls. No significant differences were observed analyzing CD4(+) and CD8(+) Treg subpopulation. Proportion and absolute counts of Th17 cells were significantly lower in pSS patient's blood. Absolute counts of CD8(+) T cells were significantly lower in pSS patients in comparison to controls and also impaired proportion and absolute counts of CD8(+) subpopulations according to CD27(+) and CD57(+) were observed. Absolute counts of NKT and NK cells were decreased in pSS with Abs. B cells proportion was increased only in blood of pSS with Abs. Lymphocyte distribution impairment can be due to genetically determined lymphopenia or lymphocyte migration from periphery to inflammatory sites or/and increased susceptibility to apoptosis.

Could the complement component C4 or its fragment C4d be a marker of the more severe conditions in patients with primary Sjögren's syndrome?

Our aim is to evaluate the complement component C4 (C4) and its fragment C4d (C4d) levels, focusing on their associations with other markers of B cells' activity in patients with primary Sjögren's syndrome (pSS). Humoral factors C4, C4d, B cell-activating factor (BAFF), κ and λ free light chains (FLCs) and IgG (by immunoassay) were investigated in 58 patients with pSS and in 28 healthy controls. We observed significantly higher levels of BAFF, κ and λ FLC and IgG, and significantly lower level of C4 in pSS patients, while the level of C4d was similar in the both groups. Significantly higher levels of BAFF, κ and λ FLCs, IgG, and significantly lower C4 level were found in anti-SSA/SSB antibodies (Abs) seropositive pSS patients' group comparing with healthy controls. Level of C4d was significantly lower in anti-SSA/SSB Abs seropositive pSS patients comparing with seronegative pSS patients and healthy controls. C4d correlated with C4, anti-SSB Abs level and κ/λ ratio. Significantly higher κ FLC and IgG levels were found in anti-SSA/SSB Abs seronegative pSS patients comparing with healthy controls. Anti-SSA/SSB seropositivity in pSS patients is associated with the decreased level of C4d. These results show that C4d can be an appropriate marker of antibody response and complement activation in pSS patients with Abs, and possibly may show the more severe condition-exhaustion of C4. Further studies are required to determine whether C4d assessment could be a relevant biomarker for the more severe condition and the worse prognosis of pSS.

Activity of T-helper cells in patients with primary Sjogren's syndrome.

AIM: To investigate the T-helper (Th1, Th2 and Th17) cell activity in the peripheral blood of patients with primary Sjögren's syndrome (pSS), non-Sjögren's sicca syndrome (nSS) and healthy controls. PATIENTS AND METHODS: Peripheral blood mononuclear cells from 34 pSS, 13 nSS patients and 13 healthy controls were stimulated, labeled for cluster of differentiation-4 (CD4), interferon-γ (IFN-γ), interleukin-4 (IL-4) and IL-17A and analyzed by flow cytometry. RESULTS: The activities of Th1 and Th17 cells in patients with pSS were similar to those of the control group. The percentage of both IFN-γ- and IL-17-producing Th17/Th1-like cells was significantly higher in the pSS, as compared to the control group, whereas that of Th2 cells was lower. A significant correlation was found between all Th-subset activities in the control group. However, in the pSS group, a correlation was found only between Th1 with Th2 and Th17 and Th17 with Th17/Th1-like. CONCLUSION: The imbalance in Th-subset activities in peripheral blood may play a role in the pathogenesis of pSS.