寻常型银屑病患者血清MMP-2、Npt、IL-18和IP-10测定的临床意义

目的：探讨寻常型银屑病（psoriasis vulgaris）患者的发病、进展与免疫学机制。方法：确诊为寻常型银屑病的患者35例为患者组;另有35名健康体检的正常成人作为对照组。血清基质金属蛋白酶-2（met-alloproteinase-2,MMP-2）、新蝶呤（neopterin,Npt）、IL-18和干扰素诱导蛋白-10（interferon induced protein-10,IP-10）四项指标水平均采用竞争酶联免疫吸附（competitive ELISA）法检测。结果：患者组治疗前MMP-2、Npt、IL-18和IP-10四项血清指标水平均较对照组升高非常显著（P均〈0.01）;治疗后MMP-2水平下降非常显著（P〈0.01）,已降至对照组水平（P〉0.05）;Npt含量也下降显著（P〈0.05）,但与对照组比较仍存在显著差异（P〈0.05）;IL-18水平经治疗后下降显著（P〈0.05）,但水平仍较对照组升高非常显著（P〈0.01）;IP-10水平治疗后下降无显著性（P〉0.05）,其含量仍较对照组升高非常显著（P〈0.01）。结论：寻常型银屑病的发生及病情进展与血清MMP-2、Npt、IL-18和IP-10四项指标水平的变化关系密切,其测定有助于了解其发病机制、病情及预后评估。     

血清新蝶呤水平对SARS病情严重程度的早期评估

目的探讨血清新蝶呤水平与SARS病程及严重程度的关系。方法应用ELISA方法检测129例SARS病人和156例健康献血者的血清新蝶呤含量。结果SARS病人血清新蝶呤水平在症状出现的首日即升高,129份急性期血清中新蝶呤含量平均值为（34.2±20.0）nmol/L,SARS恢复期病人及健康献血者血清中新蝶呤含量在正常范围,急性期血清新蝶呤含量是恢复期的5倍以上。SARS病人血清新蝶呤水平与发热期的长短及疾病的严重程度呈正相关。结论血清新蝶呤水平可作为SARS严重程度的早期指征之一。     

病毒性肝炎患者血清新喋呤检测的临床意义

研究血清新喋呤水平与慢性病毒性肝炎、肝炎肝硬化、慢性重型肝炎和感染的关系和意义。采用ELISA法检测35例慢性乙型肝炎，26例肝炎肝硬化，35例慢性重型肝炎。其中合并感染患者共19例。研究显示慢性重型肝炎组血清新喋呤水平明显高于肝炎肝硬化组和慢性肝炎组；合并感染患者血清新喋呤高于非感染患者。新喋呤水平与TBil和TBA密切相关。病毒性肝炎患者血清新喋呤水平与肝病严重程度和感染有关，对病情判断和感染诊断有参考意义。     

Interferon (IFN)‐γ‐mediated inflammation and the kynurenine pathway in relation to bone mineral density: the Hordaland Health Study

The risk of osteoporosis increases in inflammatory disorders. In cell‐mediated immune activation, interferon (IFN)‐γ stimulates macrophage release of neopterin and increases the activity of indoleamine 2,3‐dioxygenase (IDO), thereby stimulating tryptophan degradation along the kynurenine pathway. Plasma levels of neopterin and the kynurenine/tryptophan ratio (KTR) are thus markers of IFN‐γ‐mediated inflammation. Several kynurenine pathway metabolites (kynurenines) possess immunomodulatory properties. The aim of this study was to investigate associations between markers of IFN‐γ‐mediated inflammation and kynurenines with bone mineral density (BMD). The community‐based Hordaland Health Study (HUSK), with middle‐aged (46–49 years) and older (71–74 years) participants, was conducted from 1998 to 2000 (n = 5312). Hip BMD in relation to neopterin, KTR and kynurenines were investigated, using linear and logistic regression analyses. In the oldest group, neopterin (P ≤ 0·019) and KTR (P ≤ 0·001) were associated inversely with BMD after multiple adjustment. Comparing the highest to the lowest quartiles, the odds ratios of low BMD (being in the lowest quintile of BMD) in the oldest cohort were for neopterin 2·01 among men and 2·34 among women (P ≤ 0·007) and for KTR 1·80 for men and 2·04 for women (P ≤ 0·022). Xanthurenic acid was associated positively with BMD in all sex and age groups while 3‐hydroxyanthranilic acid was associated positively with BMD among women only (P ≤ 0·010). In conclusion, we found an inverse association between BMD and markers of IFN‐γ‐mediated inflammation in the oldest participants. BMD was also associated with two kynurenines in both age groups. These results may support a role of cell‐mediated inflammation in bone metabolism.     

A non-specific biomarker of disease activity in HIV/AIDS patients from resource-limited environments

Background

A general non-specific marker of disease activity that could alert the clinician and prompt further investigation would be of value in patients with HIV/AIDS, especially in resource limited environments.

Objective

To investigate the potential of neopterin as non-specific biomarker in patients with advanced HIV/AIDS.

Methods

Cross-sectional study in 105 HIV positive patients (75 on highly active antiretroviral treatment (HAART). Neopterin was assessed by enzyme linked immune-absorbent assay and cytokines by flow cytometry.

Results

Neopterin levels were significantly higher (p<0.001) for the total patient than for the control group. Significant correlations between neopterin and plasma indicators of inflammation showed neopterin to be a good indicator of active inflammatory status and of the effect of HAART on the immune system. Neopterin was superior to C-reactive protein and to individual cytokines as indicator of immune deficiency. Increased neopterin levels were associated with a decline in albumin, haemoglobin and the albumin/globulin ratio, and with increases in red cell distribution width.

Conclusions

Plasma neopterin is a good non-specific biomarker of disease activity in HIV/AIDS patients. It is a good indicator of inflammatory activity, perpetuation of inflammation-associated co-morbidities, degree of immune deficiency and has predictive value for underlying disease, and for monitoring the HAART response.     

Post-Transplant sCD30 and Neopterin as Predictors of Chronic Allograft Nephropathy: Impact of Different Immunosuppressive Regimens

Immunological monitoring for chronic allograft nephropathy (CAN) is of great potential interest. We assessed serum soluble CD30 (sCD30) together with in vitro Th2-type responses (IL-4, IL-10, CD4 helper activity) and neopterin in a prospective study of 84 renal transplant recipients with 2-year follow-up. Patients were randomized to CsA/Aza, CsA/MMF and Tacr/Aza, respectively, to analyze the effect of immunosuppression on posttransplant sCD30 and neopterin. ATG induction and acute rejections did not alter sCD30 levels whereas CMV disease was associated with transient upregulation of sCD30 (p = 0.003 at 4 months) and sustained upregulation of neopterin (corrected for graft function (Neo/CR) p = 0.005 at 2 years). Tacr versus CsA treatment proved to be an independent variable associated with downregulation of 1-year sCD30, which was positively related to Neo/CR (p = 0.007 and 0.01, respectively; logistic regression). Importantly, increased 1-year sCD30 and Neo/CR were associated with decreased glomerular filtration rate at 2 years (p = 0.02 and p < 0.0005, respectively) and evidence of CAN (p < 0.0005). High 1-year sCD30 could not be attributed to enhanced Th2-type responses and was not associated with HLA antibody formation. Our data suggest that elevated sCD30 and neopterin predict graft deterioration by CAN. Tacr effectively downregulates these responses and might be of advantage in patients with elevated sCD30 or neopterin.     

Serum neopterin as well as ferritin,soluble interleukin-2 receptor,KL-6 and anti-MDA5 antibody titer provide markers of the response to therapy in patients with interstitial lung disease complicating anti-MDA5 antibody-positive dermatomyositis

Abstract

Objective: This study identified biomarkers that can be used to assess disease activity and response to therapy in patients with interstitial lung disease complicating anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive clinically amyopathic dermatomyositis (CADM).

Methods: In 15 patients with interstitial lung disease complicating anti-MDA5 Ab-positive CADM, anti-MDA5 Ab, neopterin, interleukin (IL)-18, ferritin, and soluble interleukin 2 receptor (sIL-2R) levels were measured in cryopreserved serum specimens before and at multiple times after remission induction therapy, and their correlations were assessed.

Results: Anti-MDA5 Ab, neopterin, IL-18, ferritin, and sIL-2R levels did not differ significantly between patients who survived and those who succumbed to the disease. In many cases, serum anti-MDA5 Ab titers were over the upper limit (over 150 index value) before treatment in the usual measuring method, and gradually decreased to the normal range at stable phase. Meanwhile, serum neopterin levels (21.6 [15.3–48.3] nmol/L) were significantly elevated in newly diagnosed patients and fell to 6.8 (5–11.4) nmol/L at 6 months after treatment introduction.

Conclusions: Elevated serum neopterin as well as ferritin, sIL-2R, KL-6, and anti-MDA5 Ab titer might help identify patients with interstitial lung disease complicated with DM and might be useful in monitoring response to therapy.     

Effect of comorbidity on urinary neopterin in patients with breast carcinoma

K. MELICHAROVÁ, H. KALÁBOVÁ, L. KR?MOVÁ, L. URBÁNEK, D. SOLICHOVÁ, B. MELICHAR (2010) European Journal of Cancer Care 19 , 340–345
Effect of comorbidity on urinary neopterin in patients with breast carcinoma Urinary neopterin is increased in less than 20% of patients with breast carcinoma. Moderately increased neopterin concentrations are also known to accompany comorbid conditions commonly observed in patients with breast carcinoma, for example, diabetes mellitus or complications of atherosclerosis. In the present study, we evaluated the effect of the presence of comorbid conditions on urinary neopterin. A trend for higher neopterin concentrations was observed in patients with most of the comorbid conditions, but significantly higher neopterin was observed only in patients aged 70 years or older and in a heterogeneous group of patients with comorbidity other than diabetes mellitus, thyroid disorder, hyperlipidaemia, cardiac disorder or other malignancy. Significantly higher neopterin levels were noted in patients with two or more comorbid conditions. In conclusion, present data demonstrate an association between systemic immune activation reflected in increased urinary neopterin concentrations and age or presence of comorbid diseases in patients with breast carcinoma. A cumulative effect was observed with the presence of two or more comorbid conditions resulting in significantly increased urinary neopterin. These observations should be taken into account when interpreting the changes of parameters of systemic immune and inflammatory response in patients with breast carcinoma.