Heat shock protein 70 and anti-heat shock protein 70 antibodies in nasal secretions of patients with chronic rhinosinusitis.

BACKGROUND: The issue of heat shock protein (HSP) 70 and anti-HSP70 antibodies in chronic rhinosinusitis (CRS) has never been explored. OBJECTIVE: To determine the nasal secretion (NS) levels of HSP70 and anti-HSP70 antibodies in patients with CRS with nasal polyps (CRSwNP) and patients with CRS without nasal polyps (CRSsNP), and to evaluate their associations with CRS clinical severity and correlation with NS interleukin (IL), IL-5 and interferon λ. METHODS: CRS severity was determined by Lund-Mackay scores. Levels of immunoglobulin E (IgE), IL-4, IL-5, interferon λ, HSP70, and anti-HSP70 antibody levels in NS were measured by enzyme-linked immunosorbent assay. RESULTS: Forty-six patients with CRSsNP (25 women [54.3%] and 21 men [45.7%], mean [standard deviation {SD}]) age, 34.1 ± 12.3 years; 54 patients with CRSwNP (24 women [44.4%] and 30 men [55.6%], mean [SD] age, 37.9 ± 17.5 years). A group of 40 healthy subjects served as controls. Compared with the controls (with a mean [SD] NS HSP70 level of 0.05 ± 0.03 µg/mL), mean [SD] NS HSP70 levels in both the CRSsNP group (0.16 ± 0.07 µg/mL) and CRSwNP group (0.21 ± 0.10 µg/mL) were increased (p < 0.001). Similarly, the mean (SD) NS anti-HSP70 antibody levels were significantly higher in patients with CRSwNP (0.25 ± 0.09 optical density value [ODV]) compared with CRSsNP (0.13 ± 0.04 ODV) (p < 0.001) and healthy controls (0.14 ± 0.02 ODV) (p < 0.001). NS HSP70 in subjects with CRSwNP showed a significant positive correlation with the Lund-Mackay score (r = 0.31; p < 0.05). NS levels of either HSP70 or anti-HSP70 antibodies were strongly correlated with NS IL-4 in the CRSwNP group (r = 0.62, p < 0.001; and r = 0.69, p < 0.001, respectively). CONCLUSION: NS concentrations of HSP70 and secretory IgA anti HSP70 antibodies are increased in CRSwNP (but not in CRSsNP) and correlate positively with the Lund-Mackay score, NS IL-4, and NS IL-5.

Biomarker assessment in chronic rhinitis and chronic rhinosinusitis: Endothelin-1, TARC/CCL17, neopterin, and α-defensins.

BACKGROUND: Chronic rhinitis (CR) is characteristically divided into several major clinical phenotypes: allergic rhinitis (AR); nonallergic, noninfectious rhinopathy (NAR); and chronic rhinosinusitis (CRS). CRS has two phenotypic variants: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). An area of growing interest is to identify biologic markers that could assess different aspects of CR phenotypes. OBJECTIVE: The aim of the study was to evaluate four CR biomarkers: endothelin-1 (ET-1), thymus and activation-regulated chemokine (CCL17), neopterin, and α-defensins in subjects with AR, NAR, and CRS. METHODS: Fifty-one patients with AR, 43 patients with NAR, 46 patients with CRSsNP, 54 patients with CRSwNP, and 40 healthy controls were included. ET-1, TARC/CCL17, neopterin, and α-defensins levels in subjects' serum and nasal secretions (NS) were measured by the enzyme-linked immunosorbent assay. RESULTS: High NS levels of ET-1, TARC/CCL17, and α-defensins were characteristic for CRSwNP, although only high NS levels of neopterin were found in the CRSsNP phenotype. AR phenotype was characterized by high NS levels of ET-1 and TARC/CCL17. In the subjects with NAR, none of these biomarker levels in serum and NS differed from those of healthy controls. CONCLUSIONS: CR can be categorized by ET-1, TARC/CCL17, neopterin, and α-defensins into several disease phenotypes. Further studies are needed to better investigate pathophysiologic roles of these biomarkers in CRS.

Neuron-specific enolase in nasal secretions as a novel biomarker of olfactory dysfunction in chronic rhinosinusitis.

BACKGROUND: Olfactory dysfunction is a diagnostic criterion for chronic rhinosinusitis (CRS). During chronic inflammation and olfactory neuronal damage in CRS, it is likely that neuron-specific enolase (NSE) can leak into nasal secretions (NS) and serum. Therefore, we postulated that NSE levels in NS and in circulation may be indicative of olfactory dysfunction in CRS. OBJECTIVE: To evaluate the relationship between the NS and serum concentrations of NSE with olfactory dysfunction in subjects with CRS. METHODS: The patients with CRS were classified into two groups, depending on the presence of polyps: CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). A group of age- and sex-matched healthy volunteers served as controls. Olfactory function assessment was performed by using Sniffin' Sticks. NSE concentrations in serum and NS were analyzed by using the enzyme immunometric assay kit specific for the γ subunit. RESULTS: The study included 46 patients with CRSsNP, 25 women (54.3%) and 21 men (45.7%), mean (standard deviation [SD]) age, 34.1 ± 12.3 years; and 54 patients with CRSwNP, 24 women (44.4%) and 30 men (55.6%), mean (SD) age, 37.9 ± 17.5 years. A group of 40 healthy volunteers who were matched for age and sex served as controls. Significantly higher serum and NS levels of NSE were measured in patients with CRS compared with healthy controls (p < 0.001). In the CRSwNP group, both mean (SD) serum (83.5 ± 37.6 ng/mL) and mean (SD) NS (6.1 ± 2.3 ng/mL) levels of NSE were significantly higher than in the CRSsNP group (46.4 ± 7.3 ng/mL [p < 0.001] and 1.7 ± 0.5 ng/mL [p < 0.001], respectively). In both the CRSsNP and CRSwNP groups (but not in the healthy controls), significant negative correlations between NS NSE levels and TDI scores (r = -0.63, p < 0.001 for the CRSwNP group, and r = -0.51, p < 0.001 for CRSsNP group) were observed, which meant that higher NSE was associated with worse olfactory function. CONCLUSIONS: The study demonstrated a contribution of CRS to NSE and olfactory dysfunction.

Expression of TLR2 and TLR4 on peripheral blood monocytes during exacerbation of atopic dermatitis.

BACKGROUND: In atopic dermatitis (AD), monocytes, which accumulate in the inflamed skin, are characterized by a significantly impaired Toll-like receptors (TLR) expression and TLR2-mediated cytokine secretion. However, data on expression of TLR on monocytes of peripheral blood (PB) in AD are not available. OBJECTIVE: To investigate TLR2 and TLR4 expression on PB monocytes during AD exacerbation and to assess the relationships between TLR expressions with AD clinical severity and with serum interleukin (IL) 4, IL-10, and IL-17a levels. METHODS: The objective Scoring Atopic Dermatitis index, TLR2 and TLR4 expression on CD14(+) human leukocyte antigen-DR (HLA-DR(+)) PB monocytes by flow cytometry, serum IL-4, IL-10, IL-17a (enzyme-linked immunosorbent assay) and total immunoglobulin E levels were measured at study entry and after 4 months in patients with AD and healthy controls. RESULTS: Eighty-two patients with AD, 35 women (45.1%) and 47 men (54.9%), mean (standard deviation [SD]) age, 42.2 ± 11.5 years, were included. Thirty healthy volunteers served as controls. We observed a significant difference in the levels of TLR2 expression in the CD14(+) HLA-DR(+) PB monocytes of patients with AD (mean [SD], 51.6 ± 23.1% and 264 ± 118 cells/mm(3)) at exacerbation (but not at the end of the 4-month postexacerbation period) compared with the healthy control subjects (mean [SD], 22.3 ± 10.6% and 105 ± 50 cells/mm(3); p < 0.001). TLR4 expression in PB monocytes was significantly greater in AD (mean [SD], 50.1 ± 20.9% and 275 ± 114 cells/mm(3)) than in the healthy subjects (mean [SD], 31.2 ± 8.7% and 147 ± 41 cells/mm(3); p < 0.001) both at exacerbation and at the 4-month postexacerbation period. Significant correlations between TLR2(+) (but not TLR4(+)) PB monocytes and the objective Scoring Atopic Dermatitis index (r = 0.604, p < 0.001), serum levels of IL-17a and TLR2(+) PB monocytes (r = 0.416, p = 0.027), and IL-4 and TLR2(+) PB monocytes (r = -0.307, p = 0.014) were observed during AD exacerbation. CONCLUSION: PB CD14(+) HLA-DR(+) TLR2(+) monocytes might have a role in the skewing of a T-helper 2/T-helper 17-mediated immune response during AD flare.

Anticytokine autoantibodies in chronic rhinosinusitis.

BACKGROUND: Anticytokine autoantibodies (AAbs) involve a great panel of cytokines both in healthy subjects and in patients with various diseases, but their incidence and pathophysiologic role are widely debated. The issue of AAbs in chronic rhinosinusitis (CRS) has never been explored. OBJECTIVE: The aim of the study was to check AAbs in patients with CRS and with nasal polyps (CRSwNP) and patients with CRS and without nasal polyps (CRSsNP). METHODS: One-hundred subjects with CRS and 40 healthy controls were included. CRS severity was determined by the 22-item Sino-Nasal Outcome Test and Lund-Mackay scores. Levels of immunoglobulin A (IgA), secretory IgA, IgG, IgE, interleukin (IL) 1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-17A, and AAbs levels in subjects' serum and nasal secretions (NS) were measured by the enzyme-linked immunosorbent assay. RESULTS: Forty-six patients with CRSsNP, 25 women (54.3%) and 21 men (45.7%), mean (standard deviation [SD]) ages 34.1 ± 12.3 years; and 54 patients with CRSwNP, 24 women (44.4%) and 30 men (55.6%), mean (SD) ages 37.9 ± 17.5 years. A group of 40 healthy subjects served as controls. In both CRSsNP and CRSwNP groups, serum and NS IL-1ß, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-17A levels were higher compared with healthy controls, but there was no difference in the serum levels of cytokines between the CRSsNP and CRSwNP groups. Binding IgA antibodies against IL-1ß, IL-2, IL-5, and IL-8 were found at low levels in NS of both patients with CRSsNP and patients with CRSwNP. The highest levels of AAbs were detected against IL-5 (0.43 ± 0.38 optical density values) and IL-17A (0.51 ± 0.32 optical density values) in NS of patients with CRSwNP. In the CRSwNP group, a positive correlation was found between NS IL-5 and anti-IL-5 AAbs (r = 545; p < 0.001). Positive correlations between anti-IL-5 AAbs with NS total IgE (r = 0.424; p = 0.001) and with NS secretory IgA (r = 0.545; p < 0.001) were noted in the CRSwNP group. CONCLUSIONS: In patients with CRS, IgA class AAbs were detected in NS, whereas the highest levels of anti-IL-5 and anti-IL-17A AAbs were detected in patients with CRSwNP. Maybe these AAbs indicate disruption of immune tolerance and mucosal autoimmunity.

Plasma endothelin-1 levels during exacerbation of atopic dermatitis.

BACKGROUND: Endothelin (ET) -1 was found to participate in the pathogenesis of bronchial asthma. At present, there is no information regarding the role of ET-1 in the pathophysiology of atopic dermatitis (AD). OBJECTIVE: We assessed blood ET-1 levels during the exacerbation of AD and during the 4 months postexacerbation period, to assess the relationships between blood ET-1 levels and clinical severity of AD and pruritus. METHODS: Patients with AD and during exacerbation were recruited from the dermatology department at the Chita Medical Academy (Chita, Russia). Objective Severity Scoring of Atopic Dermatitis index, itch intensity, plasma concentrations of ET-1, and serum total immunoglobulin E levels were measured at study entry and after 4 months. RESULTS: Eighty-two patients with AD, 35 women (45.1%) and 47 men (54.9%), mean (SD) age of 42.2 ± 11.5 years were included. Thirty healthy volunteers served as controls. The mean (SD) objective Severity Scoring of Atopic Dermatitis index score during AD exacerbation was 48.8 ± 19.4 and at the 4 months postexacerbation period was 16.1 ± 8.3 (p < 0.01). Mean (SD) itch score during AD exacerbation was 6.9 ± 1.9 and, at 4 months postexacerbation was 2.6 ± 0.7 (p < 0.01). Mean (SD) plasma levels of ET-1 in patients with AD (0.74 ± 0.45 fmol/mL) were significantly higher than in healthy subjects (0.43 ± 0.24 fmol/mL) (p < 0.001). Significant correlations were found between plasma ET-1 levels with the objective Severity Scoring of Atopic Dermatitis index (r = 0.51; p < 0.001), Itch severity (r = 0.62; p < 0.001), and with serum immunoglobulin E levels (r = 0.63; p < 0.001) at the exacerbation time point in patients with AD. CONCLUSION: During AD exacerbation, plasma ET-1 levels were elevated and were positively correlated with AD clinical severity, itch intensity, and serum IgE levels.

Lymphocyte-platelet crosstalk in Graves' disease.

OBJECTIVE: Platelets can modulate lymphocytes' role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves' disease (GD). METHODS: One hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation. RESULTS: The group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3, HLA-DR+ lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10 cells/µL) than TMG group (251 ± 97 × 10 cells/µL; P < 0.05) and control group (262 ± 95 × 10 cells/µL; P < 0.05). In GD group, more platelet-bound lymphocytes (332 ± 91 /µL) were found than that in TMG group (116 ± 67/µL, P < 0.005) and control group (104 ± 58 /µL; P < 0.001). CONCLUSIONS: GD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.

New noninvasive index for evaluation of the vascular age of healthy and sick people.

We conducted a study on 861 healthy and sick subjects and demonstrated that some calculated parameters based on measurement of the dynamic light scattering (DLS) signal from the finger correlate highly with chronological age ranging from 1.5 to 85 years old. Measurements of DLS signals were obtained during both occlusion and nonocclusion of blood flow in the finger. For the nonocclusion case we found that the low-frequency component of the DLS signal significantly correlates with the biological age while the high-frequency component of the DLS signal resembles the arterial pulse-wave and does correlate with age. However, the most prominent correlation between the DLS characteristics and age was noted with the stasis stage measurements. We propose that the observed age-related phenomena are caused by alterations in local blood viscosity and interactions of the endothelial cells with erythrocytes. Further, a new noninvasive index based on the age-related optical characteristics was introduced. This noninvasive index may be used as a research and diagnostic tool to examine the endothelial and thrombolytic properties of the vascular system.