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PubMed2005

Do mice genetically selected for resistance to oral tolerance provide selective advantage for Schistosoma mansoni infection?

A highly evolved relationship exists between the parasitic flatworm Schistosoma mansoni and its vertebrate hosts that include the use of host immune signals by parasites. The S. mansoni infection was studied in two strains of mice genetically selected, over 18 generations of assortative mating, for extreme phenotypes of susceptibility (TS) and resistance (TR) to immunological tolerance. The objective was to observe whether the different host genetic backgrounds affected the outcome of experimental schistosomiasis. Fecal egg excretion, tissue egg count, worm recovery, and adult worm morphology and morphometry were monitored throughout the period of infection. TR mice presented total fecal egg excretion and thickness of tegument in adult male worms significantly higher than TS mice. Therefore, the comparative analysis of mice with extreme phenotypes of immunological response turns out to be useful in host-parasite relationship studies. Our results suggest that the TR mouse immunological profile provides a more favorable environment for the development of S. mansoni.

Animals↗
PubMed2004

Consequences of human cytomegalovirus mimicry.

The HCMV genome has evolved with its host by incorporating a series of genes that are homologous to, or functionally mimic, cellular genes. Some are designed to counteract the stress of infection on the host cell, notably the viral antiapoptotic proteins (vICA, vMIA). Others potentially help the infected cell maintain a low immunologic profile. These include virus-encoded chemokine receptors (UL33, UL78, US27, US28), FcRs (gp TRL11/IRL11, gp UL119-118), and proteins that directly or indirectly thwart natural killer cell activity (UL16, gpUL40). In addition, some viral proteins may play a role in immunopathology because of fortuitous cross-reactivity with host cell proteins. This overview discusses how these proteins affect the life of the host cell and its immediate neighbors.

Apoptosis↗
PubMed2006

Enhanced antitumor effect of dendritic cell based immunotherapy after intratumoral injection of radionuclide Ho-166 against B16 melanoma.

Internal radiotherapy with the intratumoral injection of the beta-emitting radionuclide, Holmium (Ho)-166, into B16 melanoma resulted in a reduction in size and growth rate; however, complete remission was not always achieved. Therefore, additional dendritic cell (DC) therapy was investigated to determine whether it could improve therapeutic results. Malignant melanoma was induced in mice by inoculating B16F10 cell line subcutaneously. Fifty-four mice were divided into four groups: (1) non-treated (group I, n = 11), (2) treated with Ho-166 (group II, n = 16), (3) treated with immature DCs (group III, n = 8), and (4) treated with immature DCs after Ho-166 injection (group IV, n = 19). Changes in tumor size, survival rates, and immunologic profiles were observed. Nineteen days after Ho-166 or PBS injection, mean tumor sizes in the four groups were 6044 +/- 1046, 1658 +/- 523, 3871 +/- 921, and 444 +/- 167 mm(3), respectively. We observed a significant decrease in tumor size (P < 0.05) and an increase in survival in group IV. When the B16F10 cell line was reinjected into the contralateral backs of survivors, much slower growth was observed in group IV (P < 0.05). Both tumor-specific CTL and natural killer cell activities and the infiltration of inflammatory cells into tumor tissues were found to be elevated in group IV. In addition, strong immune responses as determined by in vitro T cell proliferation, ELISA and ELISPOT assay were induced in group IV. Our results suggest that a combination of internal radiotherapy using Ho-166 and immature DCs could be used either to treat unresectable melanoma or as an adjuvant therapy after surgery.

Animals↗
PubMed2005

Subepidermal blistering disease with autoantibodies to both the p200 autoantigen and the alpha3 chain of laminin 5.

Anti-p200 pemphigoid and anti-laminin 5 mucous membrane pemphigoid are two distinct autoimmune blistering skin diseases. Patients with anti-p200 pemphigoid demonstrate circulating autoantibodies to an unknown 200-kd acidic noncollagenous glycoprotein of the lower lamina lucida, whereas anti-laminin 5 mucous membrane pemphigoid is characterized by an autoimmune response against the major basement membrane adhesion molecule laminin 5. In this report, we describe a patient who developed a recurrent nonscarring blistering eruption, affecting both skin and mucous membranes. Immunoblotting of dermal extracts and extracellular matrix of cultured keratinocytes revealed circulating autoantibodies directed to the p200 antigen and the alpha3 chain of laminin 5, respectively. The unusual clinical and immunologic profile of this case suggests that molecular specificity of circulating autoantibodies affects the clinical presentation of autoimmune subepidermal blistering skin diseases.

Antibody Specificity↗
PubMed2007

Human bladder carcinoma is dominated by T-regulatory cells and Th1 inhibitory cytokines.

PURPOSE: Immunotherapy has faced limited success, although many solutions have been proposed. Recently regulatory T cells have made a comeback in the immunological arena and the role of these cells in patients with cancer is in focus. It is under evaluation whether the immunological status of patients with cancer may affect their sensitivity to immunotherapy. We are developing immunostimulating gene therapy for treating bladder cancer. In this study we constructed an immunological profile of patients with bladder carcinoma to understand which obstacles must be circumvented. MATERIALS AND METHODS: Biopsies and blood were used to identify immune cell populations by FACS(R), histochemistry and proliferation assays, and cytokine production by polymerase chain reaction. RESULTS: Results indicate that bladder carcinoma is a Tr1 dominated tumor, as shown by the infiltration of T-regulatory cells expressing FOXP3, and the presence of tumor necrosis factor-beta and interleukin-10 mRNA copies. We further noted that circulating patient T cells were unresponsive to polyclonal T-cell activation compared to healthy donor cells. Moreover, CD4+CD25+ T cells were increased in patient blood and could suppress the expansion of allogeneic T cells from healthy donors. CONCLUSIONS: Patients with bladder carcinoma show an immunosuppressive regulatory profile, including nonresponsive T cells. Clinical protocols able to effectively counteract these mechanisms are warranted.

Humans↗
PubMed2004

Combined search for anti-beta2-glycoprotein I and anticardiolipin antibodies in antiphospholipid syndrome: contribution to diagnosis.

In this study we sought to assess (1) the diagnostic value of a combined search for anti-beta(2)-glycoprotein (abeta(2)-GPIs) and anticardiolipin antibodies (aCLs) in primary (APS I) and secondary (APS II) antiphospholipid syndrome and (2) the influence of the beta(2)-GPI preparation in the ELISA's results. abeta(2)-GPI and aCL concentrations were assessed in 70 patients with APS and compared with those in 65 patients with systemic lupus erythematosus (SLE) without clinical features of APS. In APS patients (38 with APS I, 32 with APS II), the diagnosis had to have been made at least 3 years earlier; in subjects with SLE, the diagnosis had to have been made at least 5 years earlier. All serum samples were tested for abeta(2) -GPI with the use of an in-house ELISA with an abeta(2) -GPI preparation from human plasma. Samples negative for abeta(2) -GPI were controlled with 2 additional beta(2)-GPI preparations, 1 from human serum and 1 from bovine serum. In APS, abeta(2)-GPIs were more frequent than in SLE (76% and 15%, respectively; P <.0001), mainly with IgG isotype and with significantly higher levels than those found in SLE. The specificity for APS was 92% for IgG abeta(2)-GPIs and 68% for IgG aCLs. The highest association with APS was found for the combination of the 2 markers (odds ratio 29; 95% confidence interval 10-76; P <.0001). Among the APS patients, 6 were positive for aCL only and remained negative regardless of which beta 2 -GPI preparation was used; 1 patient was aCL-negative and only positive with human beta 2 -GPI. These data emphasize the heterogeneity of the APS immunologic profile and the diagnostic possibilities of both antibodies.

Adult↗
PubMed2006

Isotype patterns of immunoglobulins: hallmarks for clinical status and tissue parasite density in Brazilian dogs naturally infected by Leishmania (Leishmania) chagasi.

The role of anti-leishmanial immune response underlying the susceptibility/resistance during canine visceral leishmaniasis (CVL) has been recognized throughout ex vivo and in vitro investigations. Recently, we demonstrated that immunoglobulin levels (Igs), as well as the parasite load are relevant hallmarks of distinct clinical status of CVL. To further characterize and upgrade the background on this issue, herein, we have evaluated, in Leishmania (Leishmania) chagasi naturally infected dogs, the relationship between tissue parasitism (skin, bone marrow, spleen, liver and lymph node), the CVL clinical status (asymptomatic (AD), with no suggestive signs of the disease; oligosymptomatic (OD), with maximum three clinical signs-opaque bristles; localized alopecia and moderate loss of weight; symptomatic (SD), serologically positive with severe clinical signs of visceral leishmaniasis), and the humoral immunological profile of anti-Leishmania immunoglobulins (IgG, IgG1, IgG2, IgM, IgA and IgE). Our major statistically significant findings revealed distinct patterns of tissue parasite density within L. chagasi-infected dogs despite their clinical status, pointing out the spleen and skin as the most relevant sites of high parasitism during ongoing CVL. Parasite density of bone marrow and spleen were the most reliable parasitological markers to decode the clinical status of CVL. Moreover, the parasite density of bone marrow better correlates with most anti-Leishmania Igs reactivity. Additionally, a prognostic hallmark for canine visceral leishmaniasis was found, highlighting strong correlation between IgG1 and asymptomatic disease, but with IgA, IgE and IgG2 displaying better association with symptomatic disease. The new aspects of this study highlighted pioneer findings that correlated the degree of tissue parasite density (low (LP), medium (MP) and high (HP) parasitism) with distinct patterns of anti-Leishmania Igs reactivity. In this scope, our data re-enforce the anti-Leishmania IgG but with IgA reactivity as the better marker for overall tissue parasitism. The association between clinical status, Ig profile and the tissue parasitism support a novel investigation on the impact of humoral immune response and susceptibility/resistance mechanism during ongoing CVL.

Animals↗
PubMed1998

Clinical and immunological study of 7 patients with minocycline-induced autoimmune phenomena.

PURPOSE: Prolonged treatment with minocycline for acne vulgaris has been associated with the development of arthralgia, arthritis, and other autoimmune phenomena. We characterized the clinical, laboratory, and immunological profiles of seven patients with this syndrome. SUBJECTS AND METHODS: Clinically the patients were studied with special emphasis on prior minocycline treatment, presenting symptoms, physical findings, course, and outcome. Laboratory tests included fluorescent antinuclear and antineutrophil cytoplasmic (ANCA) antibodies, as well as antibodies to myeloperoxidase, bactericidal permeability increasing protein, elastase, cathepsin G, lactoferrin, cardiolipin, and histone. RESULTS: All 7 patients presented with polyarthritis or arthralgia, morning stiffness, and fever after 6 to 36 months of minocycline treatment. The skin was involved in five patients (three with livedo reticularis and two with subcutaneous nodules). Two patients had chronic active hepatitis. Increased titers of perinuclear ANCA (p-ANCA) were detected in all seven patients; five patients had fluorescent antinuclear antibodies, two had antihistone autoantibodies and one had anticardiolipin antibodies. Antigenic characterization of p-ANCA disclosed antibodies to bactericidal permeability increasing protein in one patient, to elastase in three patients, and to cathepsin G in five patients. Symptoms resolved in five patients upon discontinuation of minocycline; the other two patients were treated with corticosteroids and also achieved remissions. CONCLUSION: Minocycline-induced autoimmune syndrome is characterized by reversible polyarthralgia or arthritis, morning stiffness, fever, frequent skin involvement, occasional chronic active hepatitis, and increased titers of p-ANCA with various minor p-ANCA-related antigens.

Acne Vulgaris↗
PubMed2003

Preterm low birth weight and periodontal disease among African Americans.

African Americans consistently experience higher rates of preterm and low birth weight (LBW) deliveries than do whites. LBW and preterm infants are more likely to die before their first birthday and survivors may suffer from a number of health problems. Therefore, identification of modifiable risk factors for preterm deliveries and LBW has considerable public health significance. Pregnant women's poor periodontal healtlh is emerging as one such factor. Maternal clinical periodontal status and bacteriologic and immunologic profiles related to periodontal disease have been associateted with risk of fetal growth and preterm LBW, and periodontal treatment during pregnancy has reduced the incidence of preterm deliveries. This article reviews the literature on the above association and presents data from a previously published prospective study of predominantly African Americans to show that preterm LBW deliveries are associated with higher midtrimester maternal serum antibody levels against Porphyromonas gingivalis.

Black or African American↗
PubMed2001

Detection of multiple proteins in an antibody-based protein microarray system.

A new antibody-based protein array assay is described. This assay combines the advantages of the specificity of enzyme-linked immunosorbent assays (ELISA), sensitivity of enhanced chemiluminescence (ECL) and high-throughput of microspot. In this system, the capture proteins, either antibodies or antigens are spotted onto membranes in an array format. Biological samples are then incubated with membranes. After antigens or antibodies in the samples bind to their corresponding targets and unbound proteins are washed away, the membranes are exposed to Horseradish Peroxidase (HRP)-conjugated antibody(ies). The signals are finally visualized with ECL system. Experiments demonstrate that multiple cytokines and antibodies can be simultaneously detected using this new approach. The procedure is so simple that no sophisticated equipment is required. The concept should be able to be extended to develop a high-throughput protein array system. Future applications of this new approach include direct protein expression profiling, immunological disease diagnostics and discovery of new biomarkers.

Antibodies↗
PubMed2002

[Antiphospholipid antibodies evolving into connective tissue disease: follow-up study of women with recurrent misscarriage].

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the clinical and immunologic profile, the rate of progression to connective tissue disease and the possible predictors of evolution in patients with antiphospholipid antibodies and abortions. PATIENTS AND METHOD: In a prospective follow-up study, we determined the prevalence of antiphospholipid antibodies as well as other autoimmune abnormalities and the evolution to connective tissue disease in 200 women with unexplained recurrent abortions. IgG and IgM anticardiolipin antibodies were determined by ELISA and the lupus anticoagulant was determined by means of coagulometric tests. RESULTS: Of 200 women with pregnancy losses, 69 (34.5%) had antiphospholipid antibodies. Thirty-one of 200 women (15.5%) had high or moderate positive anticardiolipin antibodies. During a mean follow-up of 32 months, 9 (13%) antiphospholipid-antibody-positive patients developed features of lupus- like disease or systemic lupus erythematosus. A low total hemolytic complement, increased circulating immune complexes and positive antinuclear antibodies (ANA) were more common in those patients evolving to a connective tissue disorder (p < 0.001, p = 0.003 and p < 0.001, respectively). Positive ANA in women with antiphospholipid antibodies predicted independently the evolution to a connective tissue disorder [Cox proportional hazard model; relative hazard = 4.92, p = 0.04]. CONCLUSIONS: A subgroup of patients with antiphospholipid antibodies and abortions may progress to a connective tissue disorder. A positive antinuclear antibody test result could be useful to identify those patients with antiphospholipid antibodies and abortions who are prone to evolve into a systemic autoimmune disease.

Abortion, Habitual↗
PubMed1998

Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.

BACKGROUND: We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. METHODS: 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. FINDINGS: Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. INTERPRETATION: We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.

Child↗
PubMed1998

Rates of flu-like infection in patients with affective illness.

Studies of immunologic profiles of depressed patients are suggestive of chronic viral infection and several investigators have found specific viral protein in some depressed patients. Moreover, several psychotropic drugs have anti-viral activity and can inhibit viral replication. In this preliminary report, we retrospectively examined the rate of reported flu-like episodes before and during psychotropic drug treatment in 236 affectively ill patients: 177 receiving lithium prophylaxis and 59 receiving chronic antidepressant medication. We observed a small but significant reduction in the mean rate of reported flu-like illness during lithium therapy (P < 0.001), with a greater reduction in men vs. women (P < 0.05). We also found a modest reduction in reported flu-like illness during chronic treatment with antidepressants (P = 0.08). Although these observations are preliminary in nature, they complement earlier reports that some psychotropic drugs may have anti-viral activity.

Antiviral Agents↗
PubMed2003

[Systemic lupus erythematosus in Tunisia. A multicentric study. About 295 cases].

PURPOSE: Systemic lupus erythematosus (SLE) is an autoimmune disease with a great clinical polymorphism. Wide variety of genetic, hormonal, immunological and environmental contributes to release the disease. Our objective was to describe and precise the epidemiological, clinical and immunological profile of this disease in Tunisia. METHOD: It is a retrospective study conducted by the Tunisian society of internal medicine during the period from January 1990 to December 1999. All patients fulfilled at least four of the revised American Rheumatism Association's criteria for SLE. RESULTS: Two hundred and ninety-five SLE have been examined (271 women, 24 men). The most frequent clinical manifestations were: articular 90%, malar rash 62%, photosensitivity 46%, seritis 32% and glomerulonephritis 56%, dominated by WHO class III and IV: 60 cases (renal biopsy was performed in 95 patients). Neurological features were observed in 14.5%. The abnormal laboratory findings were leucocytopenia 45%, lymphopenia 47%, thrombocytopenia 16% and hemolytic anemia in 6.7%. Antinuclear antibodies, anti-ds DNA and anti-Sm were at 92%, 74% and 57%, respectively. Eighty-three percent of patients were treated by steroids, and in 52 cases (18%), we added immunosuppressive drugs. Two hundred and eighteen patients were followed up with a mean follow-up duration of 51 months. Twenty-eight percent were in complete remission and in 60%, the SLE was active. In contrast, death occurred in 29 cases. CONCLUSION: Our study confirmed the clinical polymorphism of SLE, the great similarity with other studies apart the world, the gravity of renal and cardiac features and the infectious complications induced by corticosteroids.

Adolescent↗
PubMed2001

Effects of tramadol on T lymphocyte proliferation and natural killer cell activity in rats with sciatic constriction injury.

We investigated the effects of acute and chronic tramadol treatment on T lymphocyte function and natural killer (NK) cell activity in rats receiving chronic constriction injury (CCI) of the sciatic nerve. T lymphocyte function was evaluated based on concanavalin-A (ConA)- and phytohemagglutinin (PHA)-induced splenocyte proliferation. NK cell activity was measured by lactic acid dehydrogenase release assay. The effects of tramadol on thermal hyperalgesia were also assessed by measuring paw withdrawal latency (PWL) in the rats. PWL was dose-dependently reversed by tramadol after acute treatment (single subcutaneous injection) with 10, 20, and 30 mg/kg, respectively. There was no significant change among acute treatment groups in NK cell activity, whereas splenocyte proliferation induced by ConA and PHA was significantly suppressed starting from a dose of 20 mg/kg. The reversal of the thermal hyperalgesia persisted throughout a period of chronic tramadol treatment of 40 and 80 mg/kg per day, respectively, with continuous subcutaneous infusion for 7 days at a uniform rate via osmotic minipumps. No modulation of NK cell activity was found in either dose group. However, the activity of splenocyte proliferation was decreased in the 80 mg/kg per day group when compared with the saline and 40 mg/kg per day groups. These data suggest that tramadol treatment has an immunological profile different from pure mu-opioid agonists like morphine, which is known to suppress both NK cell activity and T lymphocyte proliferation at a subanalgesic dose in CCI rats. Considering analgesic and immunosuppressive effects, tramadol treatment may be a better choice than morphine for treatment of chronic neuropathic pain, particularly in patients with compromised immunity.

Analgesics, Opioid↗
PubMed2002

Glutathione transferase isoenzymes from frog (Xenopus laevis) liver and embryo.

The expression of glutathione transferase isoenzymes has been investigated in embryo and adult liver of the frog Xenopus laevis. By analysing the GST isoenzymes recovered from GSH-affinity chromatography in terms of electrophoretic mobility, HPLC elution profile, immunological reactivity, N-terminal amino acid sequence and mass spectrometry molecular mass no significant difference in the GST subunit composition between embryos and liver was found. In both tissues the same three subunits, showing similarity to mu, alpha and sigma class GSTs, are present. These results, together with those previously reported for toad (Bufo bufo), strongly support the notion that the transition from an aquatic environment to a terrestrial atmosphere containing high oxygen concentration has accompanied specific GST gene expression.

Amino Acid Sequence↗
PubMed2006

[Systemic sclerosis: epidemiology and environmental factors].

The pathophysiology of systemic sclerosis (SSc), probably multifactorial, is not yet well elucidated. Among the many endogenous and exogenous factors probably involved, environmental and occupational elements may play an essential role. SSc is a rare disease. Prevalence is estimated between 3 and 24 per 100,000 population. Reports of sporadic clusters of higher prevalence suggest environmental factors, which have not yet been defined. Silica, first suggested in 1917, plays a role in SSc development, as officially recognized in France for purposes of workers' compensation. Solvents have been associated with SSc by several rigorous case-control studies that suggest a causal role. Current data about other toxic agents (epoxy resins, vibrations, welding fumes) do not justify conclusions about their role in SSc. The severity of SSc (determined by the extent of diffuse cutaneous lesions, pulmonary involvement, and immunological profile) is probably associated with occupational exposure.

Adolescent↗
PubMed1993

Combination of interleukin-2 and gamma interferon in metastatic renal cell carcinoma.

The use of high-dose interleukin-2 (IL2), alone or in association with lymphokine activated killer cells in patients with metastatic renal cell carcinoma (MRCC) results in a 20-25% response rate. However, the toxicity of IL2 is substantial and despite many clinical trials, response rates initially reported have not been improved. The aim of this study was to evaluate a combination of IL2 and gamma interferon (IFN) in MRCC with respect to both efficacy and tolerance. IL2 was given by continuous intravenous infusion at a daily dose of 24 x 10(6) U/m2 for 2 consecutive days during 5 consecutive weeks. Gamma IFN was given subcutaneously at a daily dose of 5 x 10(6) U/m2 on the same days as IL2. 33 patients with MRCC entered the study. Clinical responses were comparable with other published series: 7 patients (21%) achieved partial response, 13 (39%) were stable and 13 had progression, despite therapy. Immunological profile observed with this regimen showed a major increase in natural killer cells which became the predominant lymphocyte population at the end of the therapy. Tolerance was good with 92.5% of the planned doses actually received by the patients. This was reflected by an early discharge from the hospital in 95% of the cycles, increasing acceptability of the regimen by the patients.

Adult↗