Increased serum levels of macrophage inflammatory protein-3α and cystatin a predict a poor prognosis of nasopharyngeal carcinoma.

This study was aimed to investigate the roles of serum macrophage inflammatory protein-3α (MIP-3α) and cystatin A in nasopharyngeal carcinoma (NPC) prognosis.The serum levels of MIP-3α and cystatin A in 140 primary NPC patients without distant metastasis were detected by enzyme-linked immunosorbent assay before and after treatment. The results were compared with those in 100 healthy controls. The log-rank test was used to compare survival curves of the 2 groups. Multivariate analysis of prognostic factors used Cox proportional hazards regression model.Serum levels of MIP-3α and cystatin A in pretreatment patients with NPC were higher than those in healthy controls. Concentrations of these 2 factors in the majority of patients after the therapy decreased to control level. Patients with high serum level of MIP-3α and cystatin A before treatment had poorer overall survival (OS), local recurrence-free survival, and distant metastasis-free survival than the ones with low level. In addition, serum pretreatment MIP-3α and cystatin A levels were independent prognostic factors for OS and distant metastasis-free survival of NPC patients; serum posttreatment MIP-3α and cystatin A levels were independent prognostic factors of local recurrence-free survival.Our results revealed that serum MIP-3α and cystatin A may be promising candidate prognostic factors for NPC, and higher serum levels of MIP-3α and cystatin A correlate with shorter probability of OS, local recurrence, and distant metastasis.

Serum cystatin C and microalbuminuria in the detection of vascular and renal damage in early stages.

BACKGROUND: The aim of this study was to assess serum cystatin C and urinary albumin in the early detection of impairment in cardiovascular and renal function. MATERIAL ANS METHODS: Cystatin C was quantified in sera from healthy people, moreover, cystatin C was quantified in a group of patients diagnosed with chronic kidney disease for predicting a measured glomerular filtration rate <60 ml/min/1.73 m2. Finally serum cystatin C and microalbuminuria were measured in patients with increasing of risk of impairment in cardiovascular and renal function (hypertension, diabetes and hyperlipidemia). RESULTS: When the serum cystatin C was quantified in a group of risk, we observe as when being increased the cystatin C, the values of the glomerular filtration rate decreased (p <0.05), the cystatin values C were increased when increasing the age of the patients (p <0.05) and cystatin C values higher than 0.95 mg/l were not observed in patient smaller than 50 years old. In the group of risk, serum cystatin C was high regarding to the values obtained in healthy people in 27.6%, microalbuminuria in the 20.3% and both parameters were high in the 14.4% of patients with a glomerular filtration rate >90 ml/min/1.73 m2, while in patients with a glomerular filtration rate 60-90 ml/min/1.73 m2, cystatin C was high in the 51.7% and the microalbuminuria only in the 6.4%. CONCLUSIONS: Determinations of serum cystatin C associated to the quantification of urinary albumin in patients with cardiovascular risk can optimize the early detection of vascular and renal damage. Cystatin C can show vascular and renal damage in patients without urinary albumin.

Serum cysteine proteases and their inhibitors in rheumatoid arthritis: relation to disease activity and radiographic progression.

This study aims to investigate the serum levels of cysteine proteases cathepsins B and H and their inhibitors stefin A, stefin B, and cystatin C, as well as traditional inflammatory markers such as C-reactive protein in patients with rheumatoid arthritis and to correlate these markers with scores of disease activity and radiographic progression. Seventy-two patients with rheumatoid arthritis were included from two previously described cohorts of patients with chronic polyarthritis. At inclusion, disease activity was assessed by a 28-joint count, patient global assessment, and serum C-reactive protein. Erosive status of hands and wrists was expressed by the Larsen score and recorded at inclusion and after 1 year. Serum levels of cathepsin B, cathepsin H, stefin A, stefin B, and cystatin C were determined by enzyme-linked immunosorbent assay. Neither cathepsin B nor cathepsin H serum levels were associated with disease activity, presence or progression of erosive disease. Number of swollen joints correlated with serum levels of stefin A and B and correlated negatively with cystatin C serum levels. Erosive disease was associated with high serum levels of C-reactive protein and stefin A and low serum levels of cystatin C. Progression of radiographic destruction was associated with high serum levels of C-reactive protein, stefin A and B, whereas serum levels of cystatin C were not associated with radiographic progression. The findings in this study support further investigation in the regulation of the activity of cathepsins and their inhibitors in erosive rheumatoid arthritis.

Identification of candidate nasopharyngeal carcinoma serum biomarkers by cancer cell secretome and tissue transcriptome analysis: potential usage of cystatin A for predicting nodal stage and poor prognosis.

Nasopharyngeal carcinoma (NPC) is usually diagnosed at advanced clinical stages, resulting in poor outcomes. To discover serum biomarkers for improved NPC diagnosis and/or management, we simultaneously analyzed the NPC cell secretome and tissue transcriptome to identify candidate genes/proteins that are highly upregulated in NPC tissues and also secreted/released from NPC cells. Among the 30 candidates identified, 11 proteins were chosen for further validation using the serum samples from NPC patients and healthy controls, including cystatin A, cathepsin B, manganese superoxide dismutase and matrix metalloproteinase 2. The results showed that serum levels of all the four proteins were indeed higher in NPC patients versus healthy controls and that the use of a three-marker panel (cystatin A, manganese superoxide dismutase and matrix metalloproteinase 2) can contribute to a better NPC detection than each marker alone. In addition, a higher pretreated serum level of cystatin A was found to be associated with a higher nodal stage and poorer prognosis of NPC patients and cystatin A could modulate the migration and invasion of NPC cells in vitro. Altogether, our results indicate that analysis of both the cancer cell secretome and tissue transcriptome is a feasible strategy for efficient identification of novel NPC serum marker panel.

Modulation of allergenicity of major house dust mite allergens Der f 1 and Der p 1 by interaction with an endogenous ligand.

Although many allergens bind endogenous molecules other than Abs in the human body, whether the interaction can modulate allergenicity has been unknown. Here, we investigated the effect of the interaction of recombinant major mite group 1 allergens (Der f 1 and Der p 1), which belong to the papain-like cysteine protease family, with an endogenous protease inhibitor, cystatin A, on their allergenicity. Cystatin A bound reduced forms of the allergens, in which the cysteine residue at the catalytic center of the protease activity was reduced by treatment with L-cysteine, but did not bind oxidized forms. Cystatin A partially inhibited the binding of IgE in mite-allergic volunteers' sera to the reduced forms, but unexpectedly enhanced the basophil histamine-releasing activity. A catalytic site-mutant of Der f 1 behaved in terms of histamine release, similarly to the reduced form. Molecular modeling showed that cystatin A interacts with the allergens within a narrow area. The results indicate that interaction with cystatin A reduces the limited number of IgE epitopes of the allergens but enhances their biological activity to release histamine, suggesting a new concept, that interaction between allergens and their endogenous ligands modulates the allergenicity even toward enhancement in the effector phase. On the other hand, i.p. immunization without alum of mice with cystatin A-treated reduced Der f 1 induced less serum Der f 1-specific IgE than immunization with reduced Der f 1 alone, suggesting that endogenous protease inhibitors suppress the induction of allergen-specific IgE, which is dependent on the enzymatic activity of cysteine protease-allergens, in the sensitization process.