Recurrent ibuprofen-induced aseptic meningitis: evidence against an antigen-specific immune response.
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Anti-Inflammatory Agents, Non-Steroidal↗
Biomedical subjects
F Spertini
Publications and source records attributed to F Spertini.
[Specific interferon-gamma assays: a modern tool for tuberculosis diagnosis].
Compared with the tuberculin skin test, the antigen-specific interferon-gamma assays, using a combination of two antigens ESAT-6 and CFP-10, has higher specificity for the diagnosis of latent tuberculosis, better correlation with exposure to M. tuberculosis, no cross-reactivity due to BCG vaccination and less towards nontuberculous mycobacterial infection. Fewer false positive results in uninfected persons avoid the costs of unnecessary therapy and its possible side effects. In low endemic areas, interferon-y assays are useful in addition of diagnostic algorithm for individuals with suspected tuberculosis. Further studies are required to evaluate the utility of the interferon-gamma assays in specialised subgroups of patients (immunocompromised, young children, patients with extrapulmonary disease,...) and as a marker of disease activity.
Humans↗
[Pathogenic mechanisms in systemic sclerosis and their therapeutical consequences. Part 1: pathogenesis].
Systemic sclerosis I(cleroderma) is a connective tissue disease caracterized by an aberrant immune activation, a vasculopathy and a fibrosis of skin and multiple internal organs (lung, kidneys, gut, among others). At present no unifying pathogenetic hypothesis exists to explain all aspects of this disease. The current hypothesis is that in patients with a favourable genetic background, certain environmental factors could produce alterations of cellular and humoral immunity and alterations of the microcirculation resulting in excessive fibrosis. A crucial component in systemic sclerosis pathogenesis is the persistent and unregulated activation of genes encoding the various extracellular matrix proteins. This is in correlation with different cytokines and growth factors produced mainly by T lymphocytes.
Fibrosis↗
[Pathogenic mechanisms in systemic sclerosis and their therapeutical consequences. Part 2: treatment].
Systemic sclerosis (scleroderma) is considered as the most severe connective tissue disease. It is characterized by an abnormal immune activation, a vasculopathy and a fibrosis of the skin and of multiple internal organs. Numerous progress in the understanding of the pathogenesis with identification of key molecules have permit to introduce novel treatments that improve the management of some aspects of the disease. ACE inhibitors are effective in resolving renal crisis. Cyclophosphamide is useful for treatment of fibrosing alveolitis. Prostaglandins, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors permit to improve the treatment of the vascular complications (digital ulcerations, pulmonary arterial hypertension) of scleroderma.
Fingers↗
Immunological basis of systemic sclerosis.
Systemic sclerosis (SSc) is a disease of unknown aetiology characterized by excessive and often progressive fibrosis in skin and multiple internal organs, an aberrant immune activation marked by multiple humoral and cellular immunological abnormalities and pronounced alterations in the microvasculature. The pathogenesis of SSc is complex and, although progress in the understanding of the multiple processes underlying SSc has been made in recent years, no single unifying hypothesis explaining all aspects of this disease exists. Recent studies have suggested that the activation of the immune system is a key stimulus to vascular abnormalities and fibrosis. Once T-cells are activated, they infiltrate the skin lesions early, and produce the profibrotic cytokine IL-4. They are also required for autoantibody production. B-cells may contribute to fibrosis, as deficiency of CD19, a B-cell signal transduction molecule, results in decreased fibrosis in animal models. In recent years, clinical advances have occurred in parallel with a better understanding of the underlying disease mechanisms. In this article, the immunological aspects and multiple altered immunological processes found in SSc are discussed.
Antibody Formation↗
-Omics for prevention: gene, protein and metabolite profiling to better understand individual disposition to disease.
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Biotechnology↗
[Skin tests in allergology: really so simple?].
In allergology, skin tests (ST) are one of the main tools. Their simplicity, rapidity of the result, low cost, near absence of risk make them complements of choice to the patient history which remains the crucial step of the diagnosis. ST demonstrate in vivo the capacity of the cutaneous mast cells to potentially react to allergens. Their sensitivity is good, some precautions have to be taken into account (no antihistaminic drugs, quality of the extracts). Specificity is also good, but a positive test (which is suggestive of the presence of IgE) not always predicts clinical allergic manifestations. Knowledge of limits and pitfalls of ST is of major importance, especially when it comes to selecting extracts for specific immunotherapy and to investigate severe anaphylactic reactions to food or drugs.
Diagnosis, Differential↗
[Oral allergy syndrome and food allergy].
To obtain a precise diagnosis of food allergy, it is essential to take a careful and detailed clinical history. This allows for directing further investigations and the patient should receive adequate information. In a research setting, recombinant allergens obtained by biotechnologies permit to reach a precise identification of allergenic proteins, with the hope of treating patients exclusively with the proteins to which they are allergic. In case of light reactions, a strict allergen avoidance is not required, but it is preferable to avoid the consumption of potentially dangerous food in isolated sites and before or during physical effort. In case of severe anaphylactic reactions with potent allergens like hazelnuts, peanuts and sea food, strict information about allergen avoidance and prescription of an emergency kit will be given.
Allergens↗
[Sarcoidosis: new therapeutic and pathogenic aspects for an "old" disease].
Sarcoidosis is a multisystemic disorder of unknown etiology characterized by non-caseating epithelioid granuloma. Clinical features are protean and the lack of a specific diagnostic test can make diagnosis difficult. The cause of this disease is still unknown but the diverse manifestations of this disorder help fuel the prevailing hypothesis that sarcoidosis has more than one cause each of which may promote a different pattern of illness. Recent progress, especially in immunology and molecular biology, has advanced our understanding of the pathogenesis of the disease and improved our ability to diagnose and treat this complex condition. This article gives an overview about current concepts in sarcoidosis and focus on immunopathogenic and therapeutic aspects.
Diagnosis, Differential↗
[Allergo-immunology. 1. Eosinophiles: old knowledge... and new pathologies].
Eosinophilic gastro-intestinal diseases (EGID) can affect the gastro-intestinal tract from the esophagus to the colon and is often associated to atopy in eosinophilic esophagitis. Proximal esophageal inflammation is of better prognosis than distal eosinophilic infiltrations (colon) that can evolve to hypereosinophilic syndrome. Interleukin-5 is a major stimulus in eosinophil recruitment to the gastro-intestinal tract as well as to the lungs. That was the rationale to initiate clinical trials with a monoclonal anti-IL-5 antibody in patients with asthma. Whereas treatment was ineffective on bronchial hyperreactivity and weakly inhibited eosinophil infiltrates, therapy with anti-IL-5 mAb resulted in a significant decrease in extracellular matrix deposition, suggesting a role for anti-IL-5 mAb in limiting bronchial remodeling.
Adolescent↗
Intravenous immunoglobulin replacement prevents severe and lower respiratory tract infections, but not upper respiratory tract and non-respiratory infections in common variable immune deficiency.
BACKGROUND: Although the dose of 400 mg/kg body weight intravenous immunoglobulins (IVIG) every 3-4 weeks is now standard for treating patients with common variable immune deficiency, studies demonstrating its long-term benefits over low 200 mg/kg dose and its effects on infectious subsets (upper vs lower respiratory vs non-respiratory infections) are rare. METHODS: All patients from a single center with the diagnosis of common variable immune deficiency and whose clinical chart was available during three successive therapeutic periods [a pre-IVIG replacement period, a low-dose (200 mg/kg every 3 weeks) and a standard-dose replacement period (400 mg/kg every 3 weeks)] were screened retrospectively. RESULTS: Seven patients followed up for a total of 116 patient-years over the three defined periods of observation were recruited. When compared with low-dose therapy, standard-dose intravenous immunoglobulin therapy raised trough IgG levels from 4.3 to 6.5 g/l and significantly decreased the overall frequency of infections, with marked effects on lower respiratory tract and severe infection number. In contrast, non-respiratory and upper respiratory infections were, in comparison, resistant to therapy. CONCLUSIONS: Overall, these data support the use of standard-dose 400 mg/kg intravenous immunoglobulin therapy, despite the high cost, to raise trough IgG levels to 5-7 g/l, but underlines that some categories of infectious events (non-respiratory, upper respiratory) may need parallel surgical or pharmacological approaches to be optimally prevented or treated.
Adult↗
Intranasal treatment with ovalbumin but not the major T cell epitope ovalbumin 323-339 generates interleukin-10 secreting T cells and results in the induction of allergen systemic tolerance.
BACKGROUND: Nasal administration of major peptide T cell epitopes gives contradictory data on the induction of peripheral tolerance. OBJECTIVE: To compare the prophylactic effect of intranasal treatment (INT) on the development of an allergic response, using either ovalbumin (OVA) or its major T cell epitope OVA 323-339 (OVAp). METHODS: BALB/c mice were treated intranasally with OVA or OVAp and subsequently immunized s.c. with OVA. Anti-OVA-specific antibody, T cell proliferation and cytokine responses were analysed. In an adoptive transfer model using OVAp specific TCR transgenic (Tg) T cells from D011.10 mice, in vivo tracking and characterization of transferred T cells in the cervical, inguinal and bronchial lymph nodes (BLN) and in the spleen were determined by FACS analysis. RESULTS: Prophylactic INT with OVA induced T cell tolerance towards subsequent OVA s.c. immunizations, inhibiting OVA specific T cell proliferation, IgE and IgG1 production, in contrast to INT with OVAp, which was unable to induce tolerance. In vivo analysis of transferred OVA-specific TCR Tg T cells showed that INT with OVA induced a preferential activation of T cells in BLN, as opposed to a broad, systemic activation with OVAp. In vivo, OVAp INT led to faster and more sustained cell division cycles than OVA INT. Ex vivo, tolerance to OVA was associated with the generation of IL-10 secreting CD4(+) T cells in BLN of OVA-treated mice only. CONCLUSION: INT with OVA but not with OVAp led to regional (as opposed to systemic) T cell activation and the induction of IL-10 secreting CD4(+) T cells in BLN, potentially critical steps in the induction of T cell-specific tolerance via the nasal route.
Administration, Intranasal↗
Reduced acute phase response after laparoscopic total extraperitoneal bilateral hernia repair compared to open repair with the Stoppa procedure.
BACKGROUND: Although laparoscopic hernia repair has been shown to be associated with less postoperative pain and an earlier recovery, there is still controversy about its role in hernia surgery. In general, laparoscopy produces less trauma to tissues than open surgery. This has been reflected by the reduced acute phase inflammatory response observed after laparoscopic surgery compared to open surgery in various settings, such as cholecystectomy or hysterectomy. The aim of this study was to evaluate the acute phase response after bilateral hernia repair by comparing the open Stoppa procedure with the laparoscopic totally extraperitoneal prosthetic repair (TEPP). METHODS: Patients were randomly allocated to either technique after written informed consent was obtained. Measurements were made of complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-1b (IL-1b), IL-6, and tumor necrosis factor-a (TNF-a) preoperatively and 4, 24, and 48 h postoperatively. VAS pain scores, consumption of analgesics, and delay before resumption of normal activities were also recorded. All the procedures were performed under general anesthesia by or in the presence of the same surgeon. RESULTS: Thirty-nine patients were included: 19 underwent the Stoppa procedure and 20 had a laparoscopic repair. The two groups were well matched for age, sex, ASA score, and preoperative values. The operation took longer (p <0.001) in the group undergoing TEPP. Patients resumed their normal activities earlier (p <0.05) after laparoscopy. In the open group, there was a larger decrease of the lymphocyte count after 4 (p <0.01) and 24 h (p = 0.04); an increased elevation of ESR after 48 h (p = 0.02); a larger increase of IL-6 after 4 (p = 0.05), 24 (p = 0.003), and 48 h (p <0.001); and a larger increase in CRP after 24 (p = 0.05) and 48 h (p = 0.01). There was no morbidity. There was no difference in postoperative IL-1b, TNF-a, total white blood cell count, polymorphonuclear count, VAS for pain, or need for analgesics between the two groups, except on the operative day. CONCLUSIONS: The acute phase inflammatory response in clearly more active after the open Stoppa procedure than after TEPP, indicating that the former is associated with increased tissue trauma. This may play a role in the earlier recovery seen after the TEPP procedure.
Acute-Phase Reaction↗
In vivo kinetics of the immunoglobulin E response to allergen: bystander effect of coimmunization and relationship with anaphylaxis.
BACKGROUND: Murine models of hypersensitivity to allergens are useful tools for the evaluation of preclinical strategies to down-regulate the IgE response. OBJECTIVE: To monitor the long-term kinetics of T and B cell responses to allergen as a function of allergen dosage and to investigate the effect of parallel immunization with a second antigen; to correlate B cell response with anaphylaxis. METHODS: CBA/J mice were sensitized every other week by subcutaneous injections of phospholipase A2 (PLA2) and/or ovalbumin (OVA) adsorbed to alum. Specific antibody isotype responses, T cell proliferation, T cell cytokine production and anaphylaxis were assessed throughout the sensitization phase. RESULTS: Low-dose immunization with PLA2 (0.1 microg) favoured a long-term, specific T helper (Th)2 response with high IgE and IL-4 production in contrast to high-dose PLA2 (10 microg) immunization, which biased the immune response towards a Th1 response with high IgG2a and low IL-4 production. Parallel immunization with an unrelated antigen (ovalbumin) had a significant bystander effect on the immunization with PLA2, which was also dose-dependent. Finally, although anaphylaxis as measured by rectal temperature drop was allergen-specific, it could be induced in the high- and low-dose immunization groups, and was not solely dependent on IgE levels. CONCLUSION: Though low-dose allergen immunization appears to induce an efficient IgE response, the intensity and quality of this response may be modulated by bystander effects of parallel immunization and does not correlate strictly with anaphylaxis. This observation has relevance to the design of clinical immunotherapy protocols using murine model-based data.
Allergens↗
CXCR3 internalization following T cell-endothelial cell contact: preferential role of IFN-inducible T cell alpha chemoattractant (CXCL11).
Chemokine receptors are rapidly desensitized and internalized following ligand binding, a process that attenuates receptor-mediated responses. However, the physiological settings in which this process occurs are not clear. Therefore, we examined the fate of CXCR3, a chemokine receptor preferentially expressed on activated T cells following contact with endothelial cells. By immunofluorescence microscopy and flow cytometry, we found that CXCR3 was rapidly internalized when T cells were incubated with IFN-gamma-activated human saphenous vein endothelial cells (HSVEC), but not with resting HSVEC. Similar results were obtained using human CXCR3-transfected murine 300-19 B cells. CXCR3 down-regulation was significantly more pronounced when T cells were in contact with HSVEC than with their supernatants, suggesting that CXCR3 ligands were efficiently displayed on the surface of HSVEC. Using neutralizing mAbs to IFN-induced protein-10 (CXCL10), monokine induced by IFN-gamma (CXCL9), and IFN-inducible T cell alpha chemoattractant (I-TAC; CXCL11), we found that even though I-TAC was secreted from IFN-gamma-activated HSVEC to lower levels than IFN-induced protein-10 or the monokine induced by IFN-gamma, it was the principal chemokine responsible for CXCR3 internalization. This correlated with studies using recombinant chemokines, which revealed that I-TAC was the most potent inducer of CXCR3 down-regulation and of transendothelial migration. Known inhibitors of chemokine-induced chemotaxis, such as pertussis toxin or wortmannin, did not reduce ligand-induced internalization, suggesting that a distinct signal transduction pathway mediates internalization. Our data demonstrate that I-TAC is the physiological inducer of CXCR3 internalization and suggest that chemokine receptor internalization occurs in physiological settings, such as leukocyte contact with an activated endothelium.
Cell Adhesion↗
Antigen-independent suppression of the allergic immune response to bee venom phospholipase A(2) by DNA vaccination in CBA/J mice.
Phospholipase A(2) (PLA(2)) is one of the major honey bee venom allergens for humans. To assess the long-term prevention of allergic reactions by DNA vaccination, a PLA(2)-CBA/J mouse model was employed using empty or PLA(2) sequence-carrying DNA plasmids. Early skin application of either DNA construct before (prophylactic approach) or after (therapeutic approach) sensitization with PLA(2)/alum led to reduced PLA(2)-specific IgE and IgG1 titers at 7 mo, with concomitant rise in IgG2a and IgG3. Splenocytes recovered at 5-6 mo after the last DNA administration exhibited a sustained IFN-gamma and IL-10 secretion and reduced IL-4 production. Recall challenge with PLA(2) boosted IFN-gamma and IL-10 secretion, suggesting the reactivation of quiescent memory Th1 lymphocytes. Mice from the prophylactic groups were fully protected against anaphylaxis, whereas 65% of the animals recovered in the therapeutic groups. Th1-polarized immune responses were also active in mice vaccinated with an empty plasmid 32 wk before sensitization with another Ag (OVA). This is the first demonstration that the Ag-coding sequence in DNA vaccine is not necessary to promote immune modulation in naive and sensitized animals for a prolonged period, and has relevance for the understanding of the innate and induced mechanisms underlying gene immunotherapy in long-term treatment of allergy.
Adjuvants, Immunologic↗
A synthetic malaria vaccine elicits a potent CD8(+) and CD4(+) T lymphocyte immune response in humans. Implications for vaccination strategies.
We report the first synthetic peptide vaccine eliciting strong CD8(+) and CD4(+) T lymphocyte responses in humans. The vaccine, representing the C-terminal region of the circumsporozoite protein of Plasmodium falciparum (amino acids 282-383) was well tolerated and strong sporozoite-specific antibodies were elicited. In addition, robust lymphocyte proliferation responses were equally elicited with concomitant in vitro production of IFN-gamma, crucial in the elimination of the parasite. Most importantly, we also observed the development of CD8(+) T lymphocyte responses decisive in the immunity to malaria. The latter finding opens new, possibly safer, avenues for vaccination strategies when a CD8(+) T cell response is needed.
Adult↗
Absence of anti-hepatitis B surface antibody after vaccination does not necessarily mean absence of immune response.
A small number of subjects vaccinated against hepatitis B do not produce anti-hepatitis B surface (HBs) antibody levels detectable by commercial assays. Others lose detectable anti-HBs at some time after vaccination. The absence of clinical hepatitis despite potential exposure to hepatitis B virus (HBV) in both kinds of subjects suggests that they might be protected by low antibody levels. However, besides anti-HBs, T helper response and memory cells which may be induced by the vaccine are certainly also important for immunity against HBV. In the present study, samples from vaccinated subjects, found to be anti-HBs negative in an initial assay, subsequently showed positive results in, respectively, 25%, 36% and 38% of the cases, when a second, third and fourth assay was used. In addition, 360 samples from "nonresponders" and from vaccinees who had lost anti-HBs, the reactivity of which was under the enzyme-linked immunoassay-cut-off value were compared to that of nonvaccinated controls. The absorbances were found to be significantly higher in the nonresponders (0.038) and in the vaccinees having lost anti-HBs (0.041), than in the controls (0.025). Such findings contribute to explaining why so-called nonresponders as well as vaccinees who have lost anti-HBs nevertheless appear to be protected.
Adult↗