SWATH-MS-based proteomics reveals functional biomarkers of Th1/Th2 responses of tropomyosin allergy in mouse models.

Type-I food allergies are hypersensitive reactions compromising the immune organs and epithelial barriers. To investigate the organ-specific proteomic alterations of the allergy responses, the spleen and intestine of mice sensitized with high (shrimp and clam) and weak (fish) allergenic tropomyosins were analyzed using sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS)-based proteomics. The results showed that Th1 and Th2 tropomyosin-induced responses in the spleen are characterized by the unique upregulation of innate (cochlin) and adaptive (Ig κ chain V-III region PC 7175) immune regulators, respectively. In the intestine, tropomyosin allergy concurred with the downregulation of 35 differentiating proteins featuring the overall impairment of metabolic pathways, absorption processes and ammonium ion responses. These data provide new functional biomarkers of tropomyosin-induced immune responses as well as candidate targets for intervention.

[Change of plasma TH1/TH2 cytokines levels in patients with hemorrhagic fever with renal syndrome].

OBJECTIVE: To observe changes in T cell subsets and TH1/TH2 secreted cytokines in the plasma of patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: Totally 22 patients with HFRS (9 mild cases and 13 moderate cases) were enrolled. Blood samples were taken 1, 4, and 12 weeks after presentation. T cell subsets were tested by flow cytometry (FCM), and the expression of cytokines in plasma were analysed with enzyme-linked immunosorbent assay (ELISA). Another 16 healthy blood donors were enrolled as the control group. RESULTS: CD3 + CD8 + T lymphocytes increased at week 1 and 4 (P < 0.01), which was more significant in mild cases than in moderate cases (P < 0.05). The change of CD3 + CD4 + T lymphocytes during the disease course were not significantly different from that in control group (P > 0.05). One week after presentation, TH1 [interleukin (IL)-2 and interferon-gamma (IFN-gamma)] and TH2 (IL-6, IL-10) cytokine productions were significantly higher in HFRS patients than in the control group (P < 0.01); IL-2 and IL-10 remained high levels during the whole observation period, and were still significantly higher than in the control group (P < 0.01). At week 4, the plasma IL-5 level was significantly higher in HFRS patients than in the control group (P < 0.01), and were still significantly higher than in the control group at week 12 (P < 0.01). At week 1 and 4, the plasma INF-gamma levels were significantly higher in moderate patients than in mild patients (P < 0.05); at week 12, the plasma IL-10 level was significantly higher in moderate patients than in mild patients(P < 0.05). CONCLUSIONS: CD3 + CD4 + T lymphocytes remarkably increases at the early stage of disease in patients with mild HFRS. The early cell mediated immune response is helpful for disease control. The cytokines INF-gamma and IL-10 increase more obviously in moderate patients, indicating that cytokines also are key pathogenic factors of HRFS.

[The dynamics of T lymphocyte subsets in hemorrhagic fever with renal syndrome].

OBJECTIVES: To investigate the T cell subsets changes in hemorrhagic fever with renal syndrome (HFRS) patients. METHODS: 22 HFRS patients who were diagnosed in Qin Huang Dao Third Hospital from April 2005 to July 2005 were enrolled in this study and divided into two groups according to clinical manifestations. T cell subsets of the 22 patients were monitored at week 1, 4 and 12. Another 56 subjects were enrolled as healthy controls. RESULTS: B cell count was normal during the 12 weeks in all the subjects. NK cell decreased significantly at week 1, and recovered at week 4 rapidly. CD(4)(+)T cell count was normal throughout the course of the disease, but the percentage of memory phenotype increased at week 1 and 4, reaching(64.1 +/- 17.5)% and (59.9 +/- 10.1)%, but recovered at week 12. CD(4)(+)CD(28)(+)T cells were normal throughout the entire study. CD(8)(+)T cell count increased dramatically at week 1 and 4, but finally recovered at week 12. The count of CD(8)(+)CD(28)(-)T cells increased significantly at week 1 in low-grade goup, but in median-grade group, this increase lagged to week 4 and was not as significant as in low-grade group. The percentage of CD(38)(+) or HLA-DR(+) subsets of CD(8)(+)T cell increased at week 1, 4. CONCLUSION: The results confirmed the relationship between HFRS progression and cellular immunity. It revealed that, at the early stage of HFRS, rapid and effective cytotoxicity T lymphocyte response may contribute to clear Hantavirus away and improve HFRS symptom.

[Change of plasma pro-inflammatory cytokines levels in patients with hemorrhagic fever with renal syndrome].

OBJECTIVE: To observe the changes of the plasma pro-inflammatory cytokines levels in patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: Enzyme-linked immunosorbent assay (ELISA) was performed to detect the plasma pro-inflammatory cytokines levels of 22 HFRS patients (9 mild cases and 13 moderate cases) 1, 4, and 12 weeks after they were diagnosed. Sixteen healthy blood donors were recruited as control group. RESULTS: The levels of interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, and IL-8 in HFRS patients were significantly higher than those in control group 1 week after they were diagnosed (all P < 0.01). The levels of IL-6 and TNF-alpha in HFRS patients returned to the normal levels four weeks after the diagnosis, while those of IL-1beta, IL-8, and IL-10 remained significantly higher than those in control group 12 weeks after the diagnosis (all P < 0.01). The IL-8 and IL-10 levels in mild HFRS patients were significantly higher than those in moderate HFRS patients at the same period (all P < 0.05). CONCLUSION: Abnormal expressions and secretion of pro-inflammatory cytokines occurs during the disease course of HFRS.

[Nosocomial fungal infections, analysis of 149 cases].

OBJECTIVE: To investigate the manifestation, diagnosis, antifungal therapy and outcome of nosocomial fungal infections. METHODS: The clinical data of 149 patients with nosocomial fungal infections admitted in the PUMC hospital from Dec. 1981 to Nov. 2001, 67 males and 82 females with an average age of 52.32 years, including the manifestation, diagnosis, treatment and outcome, were reviewed retrospectively. RESULTS: 134 out of the 149 patients suffered from deep mycoses. All cases had underlying conditions, including primary pulmonary diseases (n = 29), rheumatic disease (n = 20), hematological disease such as leukemia or lymphoma (n = 18), HIV infection/AIDS (n = 13), major surgery (n = 10), and intracerebral hemorrhage or cerebral infarction (n = 24). The predisposing factors or risk factors for deep mycoses included use of high dose broad-spectrum antibiotics over a long period (n = 37), steroids/cytotoxic chemotherapy (n = 29), immunosuppressant (n = 17), chemotherapy (n = 10), intravenous lines and incubation (n = 36), and tracheotomy or endotracheal intubation (n = 12). The infectious sites were lung, meninges, cerebral parenchyma, blood, etc. in the order of prevalence. Depending on infectious site and type of fungus, the clinical manifestations included fever (63.76%), respiratory symptom such as cough (37.58%), leucocytosis (39.6%), chest X-ray images (24.49%) etc. CNS fungal infection included meningitis, brain abscess, and granuloma. Meningitis due to Cryptococcus resembled that due to Mycobacterium tuberculosis. The main pathogenic fungal species were Candida albicans, C. tropicalis, C. parapsilosis, C. neoformans, and Aspergillus species. Amphotericin B, fluconazole, and flucytosine were used alone or in combination. The overall mortality rate was 29.53% (44/149). Out of the 149 patients 67 were cured, 29 made improvement. The incidence of fungal infection remarkably increased recently with 75 cases appearing in the past 5 years (50.34%). CONCLUSION: The incidence of fungal infection is increasing recently which is correlated with use of high dose broad-spectrum antibiotics over a long period, high dose steroids/cytotoxic chemotherapy, immunosuppressant, chemotherapy, and improvement of examination skills, etc. The main pathogens are still Candida albicans and non-albicans Candida species. Early diagnosis is very important.