Distinguishing between primary measles infection and vaccine failure reinfection by IgG avidity assay.

In this study in the Islamic Republic of Iran 365 measles cases were evaluated to distinguish between primary infection with measles and reinfection due to secondary vaccine failure. All cases previously confirmed by detection of specific IgM were tested for IgG avidity. A secondary immune response was seen in 18.4% of patients. All unvaccinated patients (16.7%) showed a primary immune response. Of 244 patients with documented vaccination, 75.8% showed a primary immune response and 24.2% showed a secondary immune response, thereby indicating a secondary vaccine failure. Almost all measles reinfections (99%) were seen in patients >10 years old, indicating that vaccination for 10-year-old children is recommended.

Distinguishing between primary measles infection and vaccine failure reinfection by IgG avidity assay

In this study in the Islamic Republic of Iran 365 measles cases were evaluated to distinguish between primary infection with measles and reinfection due to secondary vaccine failure. All cases previously confirmed by detection of specific IgM were tested for IgG avidity. A secondary immune response was seen in 18.4% of patients. All unvaccinated patients [16.7%] showed a primary immune response. Of 244 patients with documented vaccination, 75.8% showed a primary immune response and 24.2% showed a secondary immune response, thereby indicating a secondary vaccine failure. Almost all measles reinfections [99%] were seen in patients >10 years old, indicating that vaccination for 10- year- old children is recommended

Identification of peptides specific for antibodies in vitiligo using a phage library.

Patients with vitiligo produce specific autoantibodies that can be detected in their sera. These antibodies are believed to play a role in the pathogenesis of this disease. A random peptide library displayed on phage is a technique that can be used to identify the epitopes that react with monoclonal and polyclonal antibodies. We used this technique to identify the epitopes that react specifically with the vitiligo autoantibodies. By screening the random peptide phage library and using ELISA, two clones that showed a higher frequency of reactivity with the antibodies in the sera of patients with vitiligo were identified. The peptides do not show any similarity with the autoantigens so far implicated in vitiligo, indicating that these epitopes may mimic conformational epitopes in proteins.

Association of humoral immunity to human Hsp60 with the IL-6 gene polymorphism C-174G in patients with type 2 diabetes and controls.

The relationship between humoral immunity to hsp60 and type 2 diabetes along with other relevant metabolic, inflammatory and immunogenetic variables was studied in 76 non-diabetic and 74 diabetic persons aged 55-74 years selected from the population-based KORA Survey 2000. Antibodies to human hsp60 were measured in serum samples by ELISA. Hsp60 antibodies were detected in all but two individuals in a considerable range of titres (22-1,856 AU/ml). There was no significant association to age and sex, or to key clinical or metabolic parameters (BMI, WHR, HbA1c, total cholesterol, LDL cholesterol, HDL cholesterol, systolic and diastolic blood pressure, albumin, uric acid) or immunological parameters (CRP, IL-6, sIL-6R, TNFalpha, sTNFalpha R60, sTNFalpha R80). Analysis of antibody-positive individuals revealed an association between hsp60 antibodies and diabetes at borderline significance (p = 0.047), which was lost when the two antibody-negative individuals were included. Genetic analyses indicated that this association was significant in carriers of the C allele of the IL-6 promoter region polymorphism at nucleotide -174 (p = 0.02), but not in GG genotype carriers. We conclude that humoral immunity to human hsp60 may be enhanced in those diabetic patients carrying the -174C allele of the IL-6 gene. This finding may contribute to an understanding of the relationship between the -174C allele and increased risk of atherosclerosis.

Sodium alginate as a novel therapeutic option in experimental colitis.

The potential therapeutic effect of low-viscosity sodium alginate (LVA) was studied in a rat model of acute colitis induced by intracolonic administration of acetic acid. This experimental model produced a significant ulcerative colitis. Induction of colitis also significantly enhanced the serum and colonic mucosal cytokine (IL-6 and TNF-alpha) and eicosanoid (LTB4 and PGE2) levels, which paralleled with the severity of colitis. LVA solution was administered orally as drinking water at concentration of 0.5% (W/V) for 1 week. The tolerability and inhibitory effect of LVA on matrix metalloproteinase-2 (MMP-2) were tested using WEHI-164 cell line and zymography method. The results showed that LVA therapy is able to significantly reduce colonic damage score, histological lesion, serum and colonic mucosal IL-6, TNF-alpha, LTB4 and PGE2 levels in treated group compared with nontreated controls. Moreover, in vitro examinations revealed that treatment with LVA could diminish MMP-2 activity. It is concluded that LVA is able to suppress acetic acid-induced colitis in rats. Some of the action of LVA may be associated with its inhibitory effects on cytokine and eicosanoid production and MMP-2 activity. Our data suggest that LVA could potentially be a novel therapeutic option for inflammatory bowel disease.

Alteration in Matrix Metalloproteinases (MMPS) Activity in Fibroblast Cell Line by Dexamethasone: A Possible Mechanism in Corticosteroid-Induced Glaucoma.

Corticosteroids are often used as anti-inflammatory agents in a variety of inflammatory diseases. It is well established that long-term administration of corticosteroids predisposed the patients to develop glaucoma. Although the exact pathophysiology of steroid-induced glaucoma is unknown, it is assumed that Matrix metalloproteinases (MMPs) have a role in its pathogenesis. To study and estimate the pathophysiological effects of MMPs in glaucoma, we established an in vitro cell culture model. We also employed a precise proliferation assay to analyze cytotoxic effect of dexamethasone. The influence of dexamethasone on MMPs production was investigated using an in vitro gelatin Zymography. Cytotoxcity analysis of Dexamethasone revealed no significant cell death in low concentration. However, it caused 50% and 70% cell death at 80 and 100 mg/mL respectively. It also revealed an inhibitory effect on MMPs by dexamethasone in a dose dependent fashion. It may be concluded that an alteration in the level of MMPs expression by dexamethasone interferes with ocular fluid drainage and may contribute to the pathogenesis of glaucoma.

Assessment of indirect hemagglutination and zymography procedures in evaluation of gelatinase a in patients with benign and malignant prostate hyperplasia.

There are increasing data on novel tumor markers such as gelatinase A, which play a key role in tissue invasion and metastasis. Since prostate cancer is one of the common malignancies, we designed a simple and applicable Indirect Hemagglutination (IHA) test for determination of total gelatinase A in serum samples. In this study, we have analyzed the circulating form of gelatinase A (MMP-2) in patients suffering from either benign prostate hyperplasia (n= 54) or prostate cancer (n= 26) and normal individuals as control (n= 26). The gelatinolytic activity was determined by zymography followed by densitometric analysis. PSA was quantified by using a standard ELISA technique. Correlation of densitometric analysis of gelatinase A activity and IHA titer was significant at 0.01 level (p< 0.01, r = 0.916). Correlation of PSA and IHA titer was significant at 0.01 level (p< 0.01, r = 0.746). Border line IHA titer in patients with prostate cancer was 512 +/- 1 tube titer, in benign prostate hyperplasia patients was 128 +/- 1 tube titer, and the titer in normal individuals was 8 +/- 1 tube titer. These results demonstrate that IHA compared to zymography may be a better and simpler procedure in monitoring and screening patients with prostate cancer.

Interleukin-13 in Iranian patients with visceral leishmaniasis: relationship to other Th2 and Th1 cytokines.

The role of interleukin (IL)-13, a Th2 cytokine sharing many of the features of IL-4, has not previously been examined in patients with visceral leishmaniasis (VL). We examined sera from Iranian patients with VL caused by Leishmania infantum. Serum IL-13 was detected in 50% (22/44) of patients with active primary disease. In comparison, IL-10 was detected in 79.5% (35/44), interferon gamma (IFN gamma) in 38.5% (17/44), and IL-4 in only 5% (2/44) of these patients. With few exceptions all 3 cytokines were undetectable after clinical recovery following antimony therapy. Five of 7 patients (71%) who failed antimony therapy and had relapsing disease had similar levels of IL-10 to patients with active primary disease. However, with only 1 exception, IL-13, IFN gamma and IL-4 were not detected in such patients. These data suggest that relapsing disease may result from defective cellular immunity, unrelated to immunosuppression mediated by IL-10.

Comparison of the immune profile of nonhealing cutaneous Leishmaniasis patients with those with active lesions and those who have recovered from infection.

Th1-type cellular immune responses play a critical role in protection against infection with Leishmania parasites, whereas activation of Th2-type cells results in progressive disease. Cutaneous leishmaniasis caused by Leishmania major is often a self-healing disease; however, persistent nonhealing forms are also known. In the present study, we have described cell-mediated immune responses in nonhealing patients by measuring T-cell proliferation, cytokine production, and phenotypic characterization of these cells. The responses were compared with those of patients with active lesions, patients who had recovered from infection, and healthy controls. Peripheral blood mononuclear cells from patients with active lesions and recovered donors proliferated vigorously and produced Th1-type cytokine when stimulated with L. major antigens, whereas in nonhealing patients the proliferative responses were significantly lower and showed a Th2-type response to Leishmania antigens. Interleukin-10 (IL-10) production was not a feature of L. major stimulation. Flow cytometric analysis revealed that L. major antigen induced proliferation of the CD4-positive population and that these cells were the major source of gamma interferon and IL-4. These results show a distinct dichotomy in the cytokine response to L. major infection.

Localization of a protein antigen in the chicken spleen. Effect of various manipulative procedures on the morphogenesis of the germinal centre.

The time course of the localization of a protein antigen human serum albumin (HSA) into the chicken spleen after intravenous injection is analysed. Localization within seconds to the region surrounding the Schweigger-Seidel sheaths is accomplished by HSA complexes with chicken anti-HSA or by heat aggregated HSA. The localization of soluble HSA has to await the synthesis of sufficient chicken anti-HSA to accomplish localization to the same white pulp sites in the spleen at 25-30 hours after injection. By the use of complexes of HSA-anti-HSA in ten times antigen excess, the time for localization of HSA withing germinal centres was accelerated as compared with soluble HSA, so that newly formed centres containing antigen-bearing dendritic ells were seen at 48 hours instead of 72 hours after use of soluble HSA. Neonatally bursectomized and irradiated (Bx+Irr.) birds fail to localize HSA into germinal centres or to dendritic cells within the white pulp. Heat-aggregated human gamma-globulin (HGG) injected intravenously into Bx+Irr. birds rapidly localizes within seconds to the periphery of Schweigger-Seidel sheaths and at 24 hours can be seen attached to the surface of typical dendritic cells throughout the white pulp. Hence, heat-aggregated HGG can localize to dendritic cells in the absence of specific antibody. However, such localization to dendritic cells in Bx+ Irr. birds is not followed by segregation of the aggregated HGG-bearing dendritic cells within germinal centres--a further stage in the process which is presumed to require B cells and/or specific antibody. Localization of heat-aggregated HGG to white pulp dendritic ells was prevented by treatment with pepsin sufficient to destroy the ability of aggregated HGG to activate guinea-pig complement. Similary, in vivo decomplementation with a purified anticomplementary fraction (CoF) from the venom of Naja naja resulted in failure of intravenously injected HSA to localize to white pulp dendritic cells and failure of subsequent germinal centre formation. However, such decomplementation did not prevent the localization of aggregated HGG to white pulp dendritic cells. These facts are discussed in the light of hypotheses concerning germinal centre formation and the homeostasis of the antibody response in the bird.