Total IgE as a Marker for Chronic Spontaneous Urticaria

ObjectiveImmunoglobulin E (IgE) and its receptor, FcɛRI, importantly contribute to the pathophysiology of chronic spontaneous urticaria (CSU). Recent findings point to a possible role of total IgE as a marker of CSU disease activity, endotypes, and responses to treatment. The evidence in support of total IgE included in the diagnostic workup of patients with CSU has not yet been reviewed.MethodsPublications were searched via PubMed. The search terms used were “chronic urticaria” and “total IgE.” Studies were screened by titles and abstracts, and 141 were used in the review.ResultsCSU patients frequently had elevated total IgE serum levels (up to 50%), but normal or very low total IgE levels also occurred. High total IgE may represent high disease activity, longer disease duration, high chance of responding to omalizumab treatment, quick relapse after stopping omalizumab, and lower chance of responding to cyclosporine. Low IgE, in contrast, may suggest Type IIb autoimmune CSU, poor response to treatment with omalizumab and a better chance to benefits from cyclosporine treatment. Furthermore, IgE in different CSU cohorts may have different physicochemical properties that could explain differences in treatment responses to IgE-directed therapies.ConclusionThe results of our review suggest that total IgE is a valuable marker for CSU, and we recommend its assessment in the routine diagnostic workup of CSU patients.     

Interleukin 18 in the CNS

Interleukin (IL)-18 is a cytokine isolated as an important modulator of immune responses and subsequently shown to be pleiotropic. IL-18 and its receptors are expressed in the central nervous system (CNS) where they participate in neuroinflammatory/neurodegenerative processes but also influence homeostasis and behavior. Work on IL-18 null mice, the localization of the IL-18 receptor complex in neurons and the neuronal expression of decoy isoforms of the receptor subunits are beginning to reveal the complexity and the significance of the IL-18 system in the CNS. This review summarizes current knowledge on the central role of IL-18 in health and disease.     

Interleukin 8 Is a Surrogate Marker for Rapid Diagnosis of Bacteriuria

Urinary tract infection (UTI) is one of the most common sources of infection in children under 5. Rapid diagnosis is a need to avoid complications of UTI. The goal of the present study was to evaluate the use of urinary interleukin 8 (IL8) as a rapid laboratory method for diagnosis of UTI. A total of 116 children were included in the study. They were complaining of different diseases with pyuria. In addition twenty healthy children were included as control subjects. Urine samples were subjected to full chemical, cytological and bacteriological examinations. In addition, urinary IL8 was measured. Patients showed significantly elevated urine IL-8 levels (80–820 pg/ml) compared to control subjects (6–10 pg/ml) (p?<?0.0001). There was significant correlation between interleukin 8 level and white blood cells counts in urine (p?=?0.039). The mean?±?SD of urinary IL-8 was significantly increased 165.8?±?115.1 in urine with bacterial growth (Staphylococcus species and Escherichia coli) p?<?0.001 than in urine without growth. Urine with Escherichia coli (E. coli) growth had significantly higher IL 8 level than growth with other types of organisms. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value had higher level for IL8 compared to other parameters in urine examination i.e., nitrite, WBCs and RBCs (85.7%, 60%, 64%, 87%, 64% respectively). This study highlights that bacteriuria is associated with higher level of urinary interleukin 8 than pyuria without bacteriuria. Thus from this study we can conclude that IL8 can be used as rapid surrogate marker for rapid laboratory diagnosis of urosepsis.     

Interleukin 18 maintains a long-standing inflammation in coeliac disease patients

Dietary gluten induces an early response in the intestine of coeliac disease patients (CD), within a few hours, and this is driven by high levels of proinflammatory cytokines, including IFNgamma and IL-15, as has been thoroughly shown by gluten stimulation of biopsy explants. Our aim was to identify the immune mediators involved in the long-standing inflammation in untreated CD patients at diagnosis. mRNA and protein levels of TNFalpha, IL-12(p35), IL-12(p40), IL-15, IL-18 and IL-23(p19) were quantified in biopsies from active CD patients, CD patients on a gluten-free diet (GFD), healthy controls, and patients with non-CD inflammation and mild histological changes in the intestine. Biopsies from CD patients on a GFD were also stimulated in vitro with gliadin, and protein expression of IL-15 and IL-18 was analysed. Levels of IL-12 and IL-23 mRNA are nearly absent, and TNFalpha levels remain unchanged among different groups. Both the active and inactive forms of IL-18 protein have been found in all samples from active CD, and protein expression was only localized within the crypts. Levels of IL-15 mRNA remain unchanged, and protein expression, localized within the lamina propria, is found in a small number of samples. In vitro stimulation with gluten induces the expression of IL-15 and IL-18. In active CD, the early response following gluten intake characterized by high IFNgamma levels is driven by IL-18, and probably IL-15, and this alternates with periods of long-standing inflammation with moderate IFNgamma levels, maintained by IL-18 alone.     

C-Reactive Protein Measurements as a Marker of the Severity of Chronic Obstructive Pulmonary Disease Exacerbations

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the lungs. Acute exacerbations of COPD (AE-COPD) are a result of infectious or non-infectious instances. In our study, we aimed to determine whether serum C-reactive protein (CRP) levels are predictive indicators for disease severity and prognosis in hospitalized patients with AE-COPD. A total of 64 patients (36 regular ward and 28 ICU patients) were included in the study. Cases were identified and classified according to the Global Initiative for COPD. The first CRP test levels at acceptance at the ward or intensive care unit were counted in the study. CRP levels of patients in intensive care were significantly higher than those of patients in the regular ward. Mean values of CRP were detected to be 6.28?±?6.53 mg/dl in the regular ward cases and 16.9?±?12.03 mg/dl in the ICU patients (p?<?0.01). The stage of COPD did not indicate a significant difference in terms of CRP values. Mean CRP values were found to be 16.02?±?6.95 mg/dl in mortal cases and 9.76?±?11.09 mg/dl in survivors (p?<?0.01). High CRP levels were considered as a prognostic parameter and indicator of severity of AE-COPD. Increased mortality risk was found to be associated with high CRP values.     

Interleukin 1 as a cytokine inducer

Human interleukin 1 (IL 1) exerts an interferon-like antiviral activity in certain strains of human diploid fibroblasts. It is shown that this antiviral effect is indirect, in that it is mediated by production of interferon-beta. IL 1 also induces synthesis of the mRNA of another secreted protein, 26K, whose biological function is still controversial. Finally, IL 1 has bone marrow colony stimulating activity which is shown to be due to induction of colony stimulating factor in adherent phagocytic cells present in the bone marrow cultures. These findings emphasize the concept that several of the varied biological effects of IL 1 may be indirect.     

Neutrophil CD64 as a Marker of Bacterial Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are responsible for most mortality in patients with chronic obstructive pulmonary disease (COPD) and are caused mainly by bacterial infection. We analyzed and compared neutrophil CD64 expression (using the ratio of CD64 level in neutrophils to that in lymphocytes as an index), serum C-reactive protein (CRP), procalcitonin (PCT) levels, white blood cell (WBC) count, and neutrophil percentage among healthy subjects and patients with stable COPD or AECOPD. Compared with patients with COPD and healthy subjects, patients with AECOPD demonstrated significantly increased CD64 index, CRP, PCT, WBC count, and neutrophil percentage. Interestingly, CD64 index and PCT were both significantly higher in patients with AECOPD with positive bacterial sputum culture than those with negative culture. Furthermore, CD64 index and PCT were positively correlated in AECOPD, and there was also correlation between CD64 index and CRP, WBC, and neutrophil percentage. These data suggest that CD64 index is a relevant marker of bacterial infection in AECOPD. We divided patients with AECOPD into CD64-guided group and conventional treatment group. In CD64-guided group, clinicians prescribed antibiotics based on CD64 index; while in the conventional treatment group, clinicians relied on experience and clinical symptoms to determine the necessity for antibiotics. We found that the efficacy of antibiotic treatment in CD64-guided group was significantly improved compared with the conventional treatment group, including reduction of hospital stays and cost and shortened antibiotic treatment duration. Thus, the CD64 index has important diagnostic and therapeutic implications for antibiotic treatment of patients with AECOPD.     

Interleukin 18 (IL-18) upregulation in acute rejection of kidney allograft

Interleukin 18 (IL-18) is a potent proinflammatory cytokine involved in the host defence by upregulating both innate and acquired immune responses and may be of particular importance also in mechanisms of kidney allograft rejection. Immunohistochemical staining of protocol biopsies showed constitutive IL-18 expression in the epithelium of distal tubules with the induction of immunoreactivity in acute rejection patients where also proximal tubules, infiltrating leukocytes, and endothelium were strongly positive. Furthermore, serum levels of IL-18 were significantly elevated in patients with acute rejection of kidney allograft (1247+/-389 pg/l) as compared to patients with uncomplicated outcome of kidney transplantation (444+/-164 pg/l) and subjects with acute tubulointerstitial nephropathy (385+/-155 pg/l, p<0.0001 for both comparisons). Tissue culture model of renal epithelial cells expressed IL-18 mRNA constitutively and released mature IL-18 in response to TNF-alpha and IFN-gamma. We assume that upregulation of epithelial IL-18 plays an important role in immune and immunopathological reactions in renal parenchyma and contributes to rejection mechanisms of kidney allograft.     

端粒酶是一种胚胎性肿瘤标志物

本文对不同时期的人流胚胎组织和肿瘤组织端粒酶活性进行了分析。胚胎组织普遍存在端粒酶活性,其活性水平随胚胎发育时期和组织种类而异。不仅多数恶性肿瘤组织有端粒酶活性,而且某些癌前病变组织如中－重度不典型增生的肠腺癌中也可检测到瑞粒酶活性。结果证实端粒酶是一个新的胚胎性的肿瘤标志物,端粒酶活性分析对肿瘤的早期诊断具有较高的参考价值。     

Chitotriosidase as a Marker of Macrophage Stimulation

Serum chitotriosidase activity was determined in different conditions accompanied by macrophage stimulation. Stimulation of macrophages with zymosan, yeast polysaccharide carboxymethylglucan (fraction II), and lysosomotropic preparation Triton WR-1339 1.5-2.0-fold increased enzyme activity. Chitotriosidase activity in intact Wistar rats was similar to that in humans, while in CBA and A/Sn mice this parameter was 5-fold higher. Sharp increase in chitotriosidase activity in the serum from patients with type I Gaucher's disease was probably related to intense secretion of the enzyme by macrophages. Under experimental conditions, stimulation of rat and mouse macrophages (mainly liver cells) caused no increase in chitotriosidase activity typical of patients with Gaucher's disease.     

Bactericidal Activity in Whole Blood as a Potential Surrogate Marker of Immunity after Vaccination against Tuberculosis

The development of new tuberculosis (TB) vaccines will require the identification of correlates of human protection. This study examined the balance between immunity and virulence in a whole blood infection model in which intracellular mycobacterial survival was measured using BACTEC. In the blood of tuberculin-negative donors, counts of Mycobacterium tuberculosis H₃₇Ra organisms fell by 0.14 log₁₀ CFU during 96 h of whole blood culture, whereas counts of Mycobacterium bovis BCG, M. tuberculosis H₃₇Rv, and a clinical TB isolate's organisms increased by 0.13, 0.43, and 1.04 log₁₀ CFU, respectively (P < 0.001), consistent with their relative virulence. Inhibition of tumor necrosis factor alpha by the addition of methylprednisolone or pentoxifylline or removal of CD4⁺ or CD8⁺ T cells by magnetic beads had deleterious effects on immune control of intracellular growth only in the blood of tuberculin-positive donors. Repeated vaccination of eight tuberculin-negative volunteers with M. bovis BCG resulted in a 0.3 log (50%) reduction in BCG CFU counts in the model compared to baseline values (P < 0.05). Three of the volunteers responded only after the second vaccination. These experiments indicate that whole blood culture may be used to measure immunity to M. tuberculosis and that further studies of repeated BCG vaccination are warranted.     

Altered Generation of Interleukin 1 in Chronic Human Schistosomiasis Mansoni

Chronic schistosomiasis mansoni is associated with impaired cell-mediated immune responsiveness (CMI). To assess co-stimulatory factors essential in the induction phase of CMI, interleukin 1 (IL-1) concentration was determined in the sera and cell culture supernatants of Schistosoma mansoni-infected patients, and circulating monocytes were phenotyped, labelling membrane IL-1 and HLA-DP. In addition, adherent cell oxidative-burst capacity was investigated. Since involvement of IL-1 beta in the pathogenesis of severe granulomatous lesions could not be ruled out, 17 patients with intestinal schistosomiasis and 17 patients with hepatosplenic schistosomiasis were matched for intensity of infection and monitored 3-6 months after praziquantel therapy. Seventeen age- and sex-matched uninfected residents of the study area in Alagoas, Brazil, acted as controls. Whereas schistosomiasis patients and controls did not differ in the expression of monocyte surface antigens and the capacity of adherent cells to generate H2O2, IL-1 beta release by monocytes in vitro was significantly reduced in both intestinal and hepatosplenic patients. Low concentrations of circulating IL-1 beta were detected in comparable frequencies in untreated patients and controls. Three months after therapy, IL-1 beta was detectable in serum in an increased proportion of intestinal schistosomiasis patients. IL-1 release in vitro gradually increased in all patients and reached control values 6 months after therapy.     

Interleukin 18-independent engagement of interleukin 18 receptor-alpha is required for autoimmune inflammation

T helper type 1 (T(H)1) lymphocytes are considered to be the main pathogenic cell type responsible for organ-specific autoimmune inflammation. As interleukin 18 (IL-18) is a cofactor with IL-12 in promoting T(H)1 cell development, we examined the function of IL-18 and its receptor, IL-18R, in autoimmune central nervous system inflammation. Similar to IL-12-deficient mice, IL-18-deficient mice were susceptible to experimental autoimmune encephalomyelitis. In contrast, IL-18R alpha-deficient mice were resistant to experimental autoimmune encephalomyelitis, indicating involvement of an IL-18R alpha ligand other than IL-18 with encephalitogenic properties. Moreover, engagement of IL-18R alpha on antigen-presenting cells was required for the generation of pathogenic IL-17-producing T helper cells. Thus, IL-18 and T(H)1 cells are dispensable, whereas IL-18R alpha and IL-17-producing T helper cells are required, for autoimmune central nervous system inflammation.     

Interleukin 18 levels reflect the severity of acute pancreatitis

The serum interleukin 18 (IL-18) levels were significantly increased in cases of acute pancreatitis, corresponding to the severity of the disease. The IL-18 levels were also significantly correlated with the serum tumor necrosis factor alpha (TNF-alpha) and bilirubin levels. The possible involvement of IL-18 in the development of liver dysfunction in acute pancreatitis is suggested.     

非HLA因素致大鼠肾移植CAN加快模型的建立

目的建立大鼠异体肾移植慢性移植肾肾病(CAN)加快模型,为研究非HLA免疫因素及非免疫因素致CAN的病因、病理及病理生理机制提供平台。方法采用雄性Fisher大鼠和Lewis大鼠分别作为供-受体,并以假手术组作为对照,进行异体原位肾移植。受体移植术前对供肾进行强化冷缺血处理1 h,于术后4 w,8 w,12 w分别观察各受体血肌酐和移植肾组织病理变化情况。结果移植术后4周Fisher-Lewis组开始出现血肌酐的升高及移植肾CAN的病理改变,8~12周病变渐趋明显,与对照组比较有统计学差异(P<0.05)。结论以Fisher和Lewis近交系大鼠作为供-受体建立的大鼠异体肾移植CAN加快模型是一种可靠、实用和研究价值高的肾移植实验动物模型。