Altered Cell-mediated Immunity Research Articles

Disseminated life-threatening viral skin rash in a child with atopic dermatitis.

We report the case of a toddler, with a history of mild atopic dermatitis (AD) since early infancy, presented to the Giannina Gaslini, a pediatric polyclinic hospital, 14 days after measles-mumps-rubella (MMR) vaccination, for the occurrence of a disseminated vesico-pustular rash, accompanied by general malaise, fever, restlessness, and anorexia. Eczema herpeticum (EH) was diagnosed clinically and confirmed by laboratory examinations. The exact pathogenesis of EH in AD is still debated and possibly involves an inter-play between altered cell-mediated and humoral immunity, failure to up-regulate antiviral proteins, and exposure of viral binding sites through the dermatitis and an epidermal barrier failure. We hypothesize that in this particular case, MMR vaccination might have played an additional important role in the alteration of innate immune response, facilitating the manifestation of herpes simplex virus type 1 in the form of EH.

Alteration of Cell Mediated Immunity in Vitiligo Patients Using Narrow Band UVB as a Treatment.

VITILIGO is considered an autoimmune depigmenting disease. There were many evidences suggested the role of T cell mediated immunity and cytokines in the pathogenesis of the disease. The study included 20 active vitiligo patients (group 1), 20 treated patients using narrow band ultraviolet radiation B (NBUVB) (group 2), and 20 healthy control of matching age and sex (group 3). IL- 17, IL-10, TGF- Bi levels in skin tissue were measured in the three groups using ELISA technique. The results showed a significant increase in IL- 17 and TGF-Bi while there was a significant decrease in IL-10 in active vitiligo patients compared to the control (P= 0.000). Following treatment using NB-UVB, the results showed a significant decrease in the level of both IL- 17 and TGF-Bi while there was a significant increase in IL-10 (P= 0.000) compared to active vitiligo group. These statistically significant results suggest the cell mediated immune role in the disease and successful treatment by the narrow band UVB that altered the cytokines toxic effect.

Altered thymic CD4+ T-cell recovery after allogeneic hematopoietic stem cell transplantation is critical for nocardiosis

Purpose of the studyNocardia affects immunocompromised human host exhibiting an altered cell-mediated immunity. Infectious risk after allogeneic hematopoietic cell transplantation (AHCT) is significantly correlated to the recovery status of donor-derived immune system, especially CD4+ T-cells reconstitution and thymopoiesis. The purpose of this paper is to highlight a lack of cell-mediated immunity recovery for patients presenting a nocardiosis compared to a control cohort. Patients and methodsThis is a case control retrospective monocentric study. We retrospectively analyzed a monocentric cohort of 15 cases of nocardiosis after AHCT and we explored the degree of patients’ immunosuppression by phenotyping circulating lymphoid subpopulations, including NK cells, CD8+ T-cells, CD4+ T-cells and CD19+ B-cells. We focused on CD4+ T-cell subsets to appreciate thymic output, especially on naive CD4+ T-cells (NTE, CD45RA+/RO− CD4+ T-cells) and recent thymic emigrants (RTE, CD4+CD45RA+/RO−/CD31+). Infected patients were paired with a control cohort of patients with identical transplantation characteristics screened on hematological disease, AHCT conditioning, primary graft-versus-host disease (GHVD) prophylaxis, graft type, sex, age, and season at the AHCT and data concerning immunological reconstitution were compared. ResultsAt onset of nocardiosis, circulating lymphocytes and CD4+ T-cells means count were respectively 730/μL and 162/μL. CD8+ T-cells, CD56+ NK cells and CD19+ B-cells means count were respectively 362/μL, 160/μL, 112/μL. CD4+ T-cells subpopulations, naïve CD4+ T-cells production was impaired with NTE and RTE means count at 26/μL and 11/μL respectively. Comparison between nocardiosis cohort and control cohort over time highlight significant lower cellular count for lymphocytes, CD4+ T-cells, NTE and RTE with p = 0.001, p < 0.001, p < 0.001, p < 0.001 respectively. ConclusionImmune recovery monitoring follow-up after AHCT is of particular importance to identify patients susceptible to develop Nocardiosis. Efficient microbiological investigations toward Nocardia such PCR should be used in case of compatible clinical presentation.

Altered interferon-γ response in patients with Q-fever fatigue syndrome

Whether immunological mechanisms underlie Q-fever fatigue syndrome (QFS) remains unclear. For acute Q-fever, the antigen-specific interferon-γ (IFNγ) response may be a useful tool for diagnosis, and the IFNγ/interleukin(IL)-2 production ratio may be a marker for chronic Q-fever and treatment monitoring. Here we explored the specific IFNγ production and IFNγ/IL-2 ratio in QFS patients. IFNγ and IL-2 production were tested in ex-vivo stimulated whole blood of QFS patients (n = 20), and compared to those previously determined in seropositive controls (n = 135), and chronic Q-fever patients (n = 28). Also, the correlation between patient characteristics and IFNγ, IL-2, and IFNγ/IL-2 ratio was determined. QFS patients were younger (p < 0.001), but gender distribution was similar to seropositive controls and chronic Q-fever patients. Coxiella burnetii Nine Mile stimulation revealed a higher IFNγ production in QFS (median 319.5 pg/ml) than in seropositive controls (120 pg/ml, p < 0.01), but comparable to chronic Q-fever (2846 pg/ml). The IFNγ/IL-2 ratio was similar to that in seropositive controls, but lower than in chronic Q-fever patients (p < 0.01). Symptom duration was positively correlated with IL-2 production, and negatively correlated with the IFNγ/IL-2 ratio. These results point to an altered cell-mediated immunity in QFS, and suggest a different immune response than in chronic Q-fever.

English

The interaction between human papilloma virus (HPV) and human immunodeficiency virus (HIV), both sexually transmitted infections appears to be related to the alteration in cell-mediated immunity in HIV infected persons. Linkage studies of HIV/AIDs and cancer registries have indicated a 2 to 22 fold increase in cervical cancer in HIV positive women compared to HIV negative women. Data on the prevalence of HPV types in invasive cervical carcinoma (ICC) suggest that the proportion of infection with types HPV16/18 (responsible for over 70% of all cervical cancers) is similar in HIV negative and HIV positive women. The biological interaction between HIV and HPV needs further elucidation, although there is some evidence that the presence of HPV infection may be associated with increased HIV transmission. Adolescents perinatally infected by HIV are known to have higher rates of HPV infection and also have been shown to seroconvert in response to HPV vaccination with the quadrivalent vaccine, albeit to lower titers than HIV negative individuals. Anal cancer incidence is greatly increased in HIV positive individuals, particularly in HIV positive men who have sex with men. Screening for anal cancer precursors is feasible and effective; however, the impact on reduction of anal cancer remains to be demonstrated. There are ongoing studies on the safety, immunogenicity, and efficacy of current HPV vaccines in HIV positive individuals and mature data are awaited. &nbsp; Key words: human immunodeficiency virus (HIV), human papilloma virus (HPV), cervicovaginal cancer.

Nuevas técnicas in vitro en el diagnóstico de la infección tuberculosa

The biological therapies based in the anti-tumor necrosis factor-α (TNF) are an effective alternative for the treatment of chronic inflammatory diseases. However, given that anti-TNF-α therapy has been associated with reactivation of latent tuberculosis infection, a previous evaluation of the patients is required in order to avoid their progression to active TB in case of being infected. Tuberculin skin testing (TST) is used to diagnose tuberculosis infection but it has low specificity in patients who have received the BCG vaccine and low sensitivity in patients with altered cell-mediated immunity. In vitro assays based on the detection of interferon-γ (IFN) released by Tcells stimulated by specific Mycobacterium tuberculosis antigens have emerged as an option for the diagnosis of tuberculosis infection. The results to date show, that they are a viable alternative to TST thanks to their higher specificity and sensitivity. Although there are some preliminary results indicating that the IFN-γ tests could be used alone, at the moment it seems more prudent to use them in combination with the TST, considering infection when either of them is positive.

T helper and regulatory T cell cytokine profile in active, stable and narrow band ultraviolet B treated generalized vitiligo

BackgroundVitiligo is a T cell mediated autoimmune depigmenting disease. Altered cytokine concentrations have been suggested in the pathogenesis of vitiligo. MethodsT helper and regulatory T cell cytokines (IL-2, IFN-γ, IL-10, IL-13, IL-17 and TGF-β) have been estimated by ELISA and their clinical correlation was determined. The study had 3 groups: group I with 80 vitiligo patients (60 active and 20 stable), group II with 25 narrow band ultraviolet B treated vitiligo and group III with 70 healthy controls. ResultsSignificant difference was found in the serum interleukin (IL)-10, IL-13, IL-17A and TGF-β1 concentrations among 3 groups (P<0.05). In group I, serum IL-2, IL-17A concentrations were significantly increased and TGF-β1 concentrations were decreased in active vitiligo compared to stable vitiligo (P<0.05). Concentrations of IL-2, IL-10 and IL-13 (rho=−0.307, rho=−0.407, rho=−0.351 and P<0.05; respectively) were negatively- and TGF-β1 concentrations were positively-correlated (rho=0.799, P=0.001) with disease duration. Interleukin-13 concentrations were negatively- and serum TGF-β1 concentrations were positively-correlated (rho=−0.326, rho=0.244 and P<0.05; respectively) with percentage of body surface area involvement. ConclusionsIncreased concentrations of serum IL-10, IL-13, and IL-17A and decreased concentrations of TGF-β1 suggested altered cell-mediated immunity that may facilitate the melanocyte cytotoxicity in vitiligo.

Neonatal chemokine levels and risk of autism spectrum disorders: Findings from a Danish historic birth cohort follow-up study

A potential role of chemokines in the pathophysiology of Autism Spectrum Disorders (ASDs) has been previously suggested. In a recent study we examined levels of three inflammatory chemokines (MCP-1, MIP-1α and RANTES) in samples of amniotic fluid of children diagnosed later in life with ASD and controls frequency-matched to cases on gender and year of birth. In this follow-up study, levels of the same chemokines were analyzed postnatally in dried blood spot samples from the same subjects utilizing the Danish Newborn Screening Biobank. Crude estimates showed decreased levels of RANTES. In the adjusted estimates, no differences were found in levels of the three examined chemokines in ASD cases compared to controls. Our findings may cautiously suggest an altered cell-mediated immunity during the early neonatal period in ASD. Further research is needed to examine the relationship between maternal/fetal and neonatal chemokine levels and their role in ASD.

Toxicopathological evaluation in Wistar rats (Rattus norvegicus) following repeated oral exposure to acephate

The present study was carried out to evaluate the effects of exposure at different doses of acephate on hematology, blood biochemistry, oxidative stress and immune system of Wistar rats. The experiment was carried out on 40 Wistar rats, which were divided in four groups. Animals of the three treatment groups were given with different sublethal doses (1/40th, 1/20th, 1/10th of lethal dose 50 value) of acephate by oral gavage. The hematology, blood biochemistry, oxidative stress marker, humoral immune response and cell-mediated immunity were evaluated following acephate exposure. Significant alteration in hematological parameters was not observed following different doses of acephate; however, significant alteration in alkaline phosphatase, gamma glutamyl transferase, acetyl cholinesterase, lipid peroxidase and superoxide dismutase was observed in medium- and high-dose group animals. Nonsignificant decrease in antibody titer in animals exposed to high dose has been observed compared with animals of control group. However, significant alteration in cell-mediated immunity was not observed in animals treated with acephate at different doses.

Interferon γ Assays in the Diagnosis of Tuberculosis Infection in Psoriasis Patients Who Are Candidates for Biologic Therapies

Although there is no doubt that biologic agents are an effective alternative for the treatment of moderate and severe psoriasis, anti-tumor necrosis factor α therapy has been associated with reactivation of latent tuberculosis infection. Tuberculin skin testing (TST) is used to diagnose tuberculosis infection but it has low specificity in patients who have received the Mycobacterium bovis BCG vaccine and low sensitivity in patients with altered cell-mediated immunity. In vitro assays based on the detection of interferon γ released by T cells stimulated by specific Mycobacterium tuberculosis antigens have emerged as an option for the diagnosis of tuberculosis infection. The results to date show that they are a viable alternative to TST thanks to their higher specificity and sensitivity. Furthermore, these assays are also proving to have high negative predictive value, meaning that we might be able to use them without TST in the short to medium term.

Técnicas basadas en la detección de IFN-γ en el diagnóstico de la infección tuberculosa en pacientes con psoriasis candidatos a terapias biológicas

Although there is no doubt that biologic agents are an effective alternative for the treatment of moderate and severe psoriasis, anti-tumor necrosis factor α therapy has been associated with reactivation of latent tuberculosis infection. Tuberculin skin testing (TST) is used to diagnose tuberculosis infection but it has low specificity in patients who have received the Mycobacterium bovis BCG vaccine and low sensitivity in patients with altered cell-mediated immunity. In vitro assays based on the detection of interferon γ released by T cells stimulated by specific Mycobacterium tuberculosis antigens have emerged as an option for the diagnosis of tuberculosis infection. The results to date show that they are a viable alternative to TST thanks to their higher specificity and sensitivity. Furthermore, these assays are also proving to have high negative predictive value, meaning that we might be able to use them without TST in the short to medium term.

21 Days head-down bed rest induces weakening of cell-mediated immunity – Some spaceflight findings confirmed in a ground-based analog

Several studies indicate a weakening of cell-mediated immunity (CMI) and reactivation of latent herpes viruses during spaceflight. We tested the hypothesis that head-down bed rest (HDBR), a ground-based analog of spaceflight, mimics the impact of microgravity on human immunity. Seven healthy young males underwent two periods of 3weeks HDBR in the test facility of the German Aerospace Center. As a nutritional countermeasure aimed against bone demineralisation, 90mmol potassium bicarbonate (KHCO3) was administered daily in a crossover design. Blood samples were drawn on five occasions. Whole blood was stimulated with antigen i.e. Candida albicans, purified protein derivative (PPD) tuberculin, tetanus toxoid and Cytomegalovirus (CMV) (CMV-QuantiFERON). Flow cytometric analysis included CD4+CD25+CD127−FOXP3+ regulatory T cells (Tregs), γδ T cells, B cells, NK cells and dendritic cells. In one of the two bed rest periods, we observed a significant decrease in production of interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) following phytohemagglutinin (PHA) stimulation, with a rapid normalization being observed after HDBR. The cytokine levels showed a V-shaped pattern that led to a relativeTh2-shift in cytokine balance. Only three individuals responded to the specific T cell antigens without showing signs of an altered response during HDBR, nor did we observe reactivation of CMV or Epstein–Barr virus (EBV). Of unknown significance, dietary supplementation with KHCO3 counteracted the decrease in IL-2 levels during HDBR, while there was no impact on other immunological parameters. We conclude that discrete alterations in CMI may be induced by HDBR in selected individuals.

Herpes Zoster Vaccination in People Aged 50–59 Years

Herpes zoster (or shingles), an infectious disease caused by reactivation of latent varicella-zoster virus (VZV) in the dorsal root or cranial nerve ganglia, typically manifests as unilateral acute pain accompanied by a vesicular rash. The acute pain and rash usually resolve within 2– 4 weeks without treatment. Postherpetic neuralgia, commonly defined as pain that lasts .3 months after the onset of rash or cutaneous healing, is the most common and feared complication and can persist occasionally for years in some patients. In addition to postherpetic neuralgia, some patients may suffer from ocular, hearing, or other serious neurological complications [ 1 , 2 ]. Age-related decline in cell-mediated immune responses is a major risk factor of herpes zoster as well as postherpetic neuralgia. The annualized incidence of herpes zoster was 4.6, 6.9, 9.5, and 10.9 per 1000 people aged 50–59, 60–69, 70–79, and $80 years, respectively [ 3 ]; the corresponding proportion of patients who had postherpetic neuralgia in each age group was approximately 5%, 10%, 17%, and 20%, respectively [ 4 ]. People with immunosuppressive illness or those receiving immunosuppressive therapy are more vulnerable to herpes zoster and more likely to develop postherpetic neuralgia. The annualized incidence of herpes zoster was 29.4 per 1000 men seropositive for human immunodeficiency virus (HIV) and 2.0 per 1000 HIV-seronegative men [ 5 ]. Diabetes mellitus, often accompanied by altered cell-mediated immunity, was associated with an increased risk of herpes zoster and prescriptions of opioids within a year of diagnosis of shingles [ 6 ].

Rhodococcus equiInfection After Lung Transplantation

Rhodococcus equi is an emerging opportunistic pathogen in immunocompromised patients. A lung-transplant recipient developed weight loss, nonproductive cough, dyspnea, and somnolence. Computed tomogram showed a pulmonary nodule and pleural changes in the right allograft that was due to R. equi infection. Alteration of cell-mediated immunity is a predisposing risk factor for R. equi infection in humans. Our patient developed R. equi infection soon after a course of high-dose corticosteroids for acute allograft infection and animal exposure. A course of intravenous vancomycin followed by single-agent long-term therapy with oral ciprofloxacin was successful.

Peripheral blood mononuclear cell transcriptome profiles suggest T-cell immunosuppression after uncomplicated mechanical circulatory support device surgery

Mechanical circulatory support device (MCSD) surgery in patients with advanced heart failure patients is often complicated by infections that are linked to altered cell-mediated immunity. Using a transcriptome-wide peripheral blood mononuclear cell (PBMC) gene expression profiling approach, we analyzed expression patterns directly before and after MCSD implantation in 11 patients who had an uncomplicated course after MCSD implantation (Day 0-24 hours before, Day 1-24 hours after, and Day 7-1 week after implantation). Data were analyzed using Significance Analysis of Microarrays (SAM) and High-Throughput GoMiner on post-implantation profiles (Day 1, Day 7) in comparison with baseline (Day 0). Day1 profiles included differential expression of 821 genes (SAM, FDR <0.1, fold change >1.5), enriching >60 Gene Ontology (GO) categories. Grouping by component genes revealed GO clusters, which we term “interleukin related” (primarily upregulated), “T-cell related” (primarily downregulated), and “apoptosis related” (both up- and down-regulated genes). Day 7 profiles included GO categories related to repair processes. In conclusion, transcriptome-wide expression profiling of PBMCs suggests a response pattern to MCSD implantation of inflammatory activation and simultaneous T-cell suppression.

Toxoplasmose disséminée sévère avec choriorétinite atypique : à propos d’un cas de primo-infection

The clinical diagnosis of ocular toxoplasmosis is based on clinical features and biological tests: polymerase chain reaction (PCR) and the determination of intraocular specific antibody secretion (Goldmann-Witmer coefficient) on aqueous humor. Older patients may have a higher prevalence of ocular involvement and more severe ocular disease during the acute phase of recently acquired systemic infection because of altered cell-mediated immunity. Moreover, the genotype of the infecting parasite (particularly involving neotropical Type I Toxoplasma gondii strain), appears to be an important determinant of disease severity.

Abcès du tronc cérébral à Listeria monocytogenes

Introduction Listeriosis commonly involves the central nervous system. Meningoencephalitis and rhomboencephalitis are the most frequent manifestations. Brain abscesses are rare. Case report We report the case of a 63-year-old man treated with steroids for a long period; he was hospitalized for hemiparesis, confusion and fever. Clinical examination revealed meningeal signs, right hemiparesis and Parinaud syndrome. Initial CT scan was normal. The CSF contained 520 white cells/mm 3 with predominance of polymorphonuclear neutrophils. An acute meningo- rhombencephalitis in an immunodepressed patient was suggested. The diagnosis of listeriosis was confirmed by blood cultures. Amoxicillin and gentamycin were started. The outcome on day 4 was severe with coma and tetraparesis. Brain MRI revealed a left peduncle abscess which descended deep into the brain reaching the internal capsule. The final clinical outcome involved residual right hemiparesis and left oculomotor nerve (III) palsy. Conclusion Brain stem abscess is an uncommon form of listerial central nervous system infection. Listeria monocytogenes infection should be considered in patients with altered cell-mediated immunity that develop local neurologic deficits, a diagnosis which pursued rapidly with repeated blood cultures. Successful treatment requires early antibiotic therapy with ampicillin and gentamycin.

CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms

Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity (CMI), the determinants of CMI in humans are poorly understood. Here we demonstrate that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence CMI in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered CMI in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and CMI. These results identify CCL3L1 and CCR5 as major determinants of CMI and demonstrate that these host factors influence HIV pathogenesis through their effects on both CMI and other viral entry-independent mechanisms.

Effect of 2 anesthetic techniques on the postoperative proinflammatory and anti-inflammatory cytokine response and cellular immune function to minor surgery

Study Objective The aim of this study was to investigate the influence of 2 established anesthetic techniques: total intravenous anesthesia and balanced inhalation anesthesia (BAL) on the perioperative-induced changes of peripheral blood mononuclear cells (PBMCs), changes in lymphocyte subsets, and the balance of proinflammatory and anti-inflammatory cytokines. Design This is a prospective, randomized, clinical comparison study. Settings This study was set at a university hospital. Patients This study involved 50 patients with American Society of Anesthesiologists physical status I who were scheduled for elective minimal invasive partial diskectomy. Interventions There was no intervention involved in this study. Measurements Changes in differential counts, lymphocyte subsets, and proliferation rates were determined before surgery and in the early postoperative period. Plasma concentrations of proinflammatory cytokines (IL-2, IL-6, IL-12, interferon γ) and anti-inflammatory cytokines (IL-10, IL-1RA, transforming growth factor β), and plasma concentrations of cortisol, epinephrine, and norepinephrine were measured before, during, and after surgery. Main Results Absolute number of CD3 +, CD4 +, and CD8 +, and expression of HLA-DR and activation marker CD25 +, CD26 +, and CD69 + decreased more in response to surgery after BAL. Changes in distribution of T-lymphocyte cells seem to be in part related to severe postoperative pain. Plasma concentration of IL-6 significantly increased during and after surgery with BAL without relation to pain. Conclusion Anesthetic management may have varying influences on the postoperative immune response. Surgery-induced inflammatory response and alteration in cell-mediated immunity seem to be more pronounced after BAL. These effects were attributed to the enhanced stress response after BAL.

NOCARDIOSIS IN AN OTHERWISE IMMUNOCOMPETENT PREGNANT FEMALE

INTRODUCTION: Nocardiosisis a bacterial infection seen predominantly in patients with altered cell-mediated immunity (CMI). We describe the first case of pulmonary Nocardiosis in an immunocompetent pregnant female presenting as hemoptysis and discuss the pertinent aspects of this patients care.