Immunological Symptoms Research Articles

Tendencias de la personalidad y síntomas somáticos

Esta investigación tuvo por objetivo averiguar si hay diferencias en la manifestación de síntomas somáticos, tomando en cuenta el tipo de tendencia de personalidad [ego(+) o ego(-)] y el género. Se aplicó el Cuestionario de Tendencias de la Personalidad (CTP; Valdez, 2009) y la Escala de Síntomas Somáticos (ESS-R; Sandín & Chorot, 1995). Los análisis de datos fueron hechos sobre una muestra no probabilística intencional de 128 adultos (70 hombres y 68 mujeres), de los cuales 64 pertenecían al tipo ego(+) y 64 al tipo ego(-). Se encontraron diferencias significativas por estilos de personalidad. Los participantes de tipo ego(-) fueron más sintomáticos, sufriendo más síntomas inmunológicos, gastrointestinales, alérgicos, hipertensivos y renales. Con base en la interrelación dentro de cada muestra de tipo de personalidad, los síntomas que involucran al sistema inmune se definieron más en el tipo ego(–) y los músculo-esqueléticos y genitourinarios en el tipo ego(+). También hubo diferencias por género, pero sin interacción con el tipo de personalidad. Las mujeres fueron más sintomáticas que los hombres. Así los tipos de personalidad y el género, como factores independientes, permiten considerar estrategias diferenciales de intervención en síntomas somáticos.

Human α‐mannosidase produced in transgenic tobacco plants is processed in human α‐mannosidosis cell lines

Deficiency in human lysosomal α-mannosidase (MAN2B1) results in α-mannosidosis, a lysosomal storage disorder; patients present a wide range of neurological, immunological, and skeletal symptoms caused by a multisystemic accumulation of mannose-containing oligosaccharides. Here, we describe the expression of recombinant MAN2B1 both transiently in Nicotiana benthamiana leaves and in the leaves and seeds of stably transformed N. tabacum plants. After purification from tobacco leaves, the recombinant enzyme was found to be N-glycosylated and localized in vacuolar compartments. In the fresh leaves of tobacco transformants, MAN2B1 was measured at 10,200 units/kg, and the purified enzyme from these leaves had a specific activity of 32-45 U/mg. Furthermore, tobacco-produced MAN2B1 was biochemically similar to the enzyme purified from human tissues, and it was internalized and processed by α-mannosidosis fibroblast cells. These results strongly indicate that plants can be considered a promising expression system for the production of recombinant MAN2B1 for use in enzyme replacement therapy.

P01-281 - Psychopathological features in somatic asymptomatic HIV positive patients

BackgroundMany studies on samples of HIV-positive patient's shows correlation of psychiatric symptoms and medical and immunological symptoms of HIV infection. Also, presence of psychiatric distress was showed in some somatic diseases, especially the ones which lead to chronic.AimThe aim was to examine presence of psychopathological symptoms among HIV-1 infected patients which haven’t developed AIDS, in comparison to hepatitis B or C infected patients.MethodsSample for consisted of 60 patients: a) 30 somatic asymptomatic HIV-1 seropositive patients who constituted study group, and b) 30 patients infected with hepatitis B or C which constituted control group. All of them have been assessed on the presence of psychiatric symptoms by the SCL-90 (The Symptom Checklist 90). After the assessment those two groups were compared by student's t test on every subscale and total score.ResultsResults of the study showed that patients in both groups exhibited moderate presence of psychopathological symptoms, especially symptoms of depression, anxiety and interpersonal sensitivity. Moreover, patients with HIV exhibited obsessive-compulsive symptoms. Results showed that there are no statistically significant differences in presence psychopathological symptoms between somatic asymptomatic HIV-positive patients and patients infected with hepatitis B or C.ConclusionBased on the results of this study it could be concluded that, beside the moderate presence of psychopathological symptoms in the samples of somatic asymptomatic HIV-positive patients and hepatitis B or C infected patients, there is no statistically significant difference in those samples of patients.

Association of peroxisome proliferator-activated receptor-gamma gene polymorphisms with the development of asthma

The peroxisome proliferator-activated receptors (PPAR) are the nuclear hormone receptor superfamily of ligand-activated transcriptional factors. PPAR-gamma (PPARG) activation downregulates production of Th2 type cytokines and eosinophil function. Additionally, treatment with a synthetic PPARG ligand can reduce lung inflammation and IFN-gamma, IL-4, and IL-2 production in experimental allergic asthma. In patients with asthma, PPARG gene expression is known to be associated with the airway inflammatory and remodeling responses. Thus, genetic variants of PPARG may be associated with the development of asthma. We genotyped two single nucleotide polymorphisms on the PPARG gene, +34C>G (Pro12Ala) and +82466C>T (His449His), in Korean subjects (839 subjects with asthma and 449 normal controls). Association analysis using logistic regression analysis showed that +82466C>T and haplotypes 1(CC) and 2(CT) were associated with the development of asthma (p=0.01-0.04). The frequency of PPARG-ht2 was significantly lower in the patients with asthma compared to the normal controls in codominant and dominant models (p=0.01, p(corr)=0.03 and p=0.02, p(corr)=0.03, respectively). Conversely, the frequency of PPARG-ht1 was significantly higher in the patients with asthma compared to the normal controls in the codominant model [p=0.04, OR: 1.27 (1.01-1.6)]. In addition, the rare allele frequency of +82466C>T was significantly lower in patients with asthma in comparison to normal controls in the codominant model (OR: 0.78, p=0.04). Thus, polymorphism of the PPARG gene may be linked to an increased risk of asthma development.

Autism and Immunity: Revisited Study

Autism spectrum disorder is of interest neurochemically because it represents a relatively homogeneous disorder with regard to disease development, abnormal cognitive development and intellectual development disturbance. A consistent finding in autistic children is a high number of mast cells and a high level of serotonin which is also found at elevated concentrations in the urine of autistic patients. In addition, a dysfunction of clinical conditions, such as gastrointestinal and immunological symptoms, is frequently noted in autistic children, however, IgE does not appear to be prevalent in these children but probably an increase of cytokines/chemokines produced by mast cells at an early age may play an important role. Therefore an immune hypothesis, involving also autoimmunity, is one possible pathogenetic mechanism in autism. In conclusion, mast cell activation could contribute to immune and neuroinflammatory abnormalities that are evident in patients with autism spectrum disorders.

Systemic PPARγ Ligation Inhibits Allergic Immune Response in the Skin

We have shown previously that specific ligands of the peroxisome proliferator-activated receptor-gamma (PPARgamma) inhibit the systemic allergic immune response. The objective of this study was to investigate the impact of PPARgamma-ligand treatment on the local allergic immune response. We established a murine model exhibiting clinical and histological features of AD-like skin lesions with high reproducibility. In this model, the PPARgamma ligand was applied in an either preventive or therapeutic manner via systemic and local routes. The affected skin areas were assessed by standardized skin score, histological analyses, and immunohistochemical examinations. Our data show that systemic application of PPARgamma ligand by a preventive protocol led to significantly reduced onset of eczematous skin lesions. This was confirmed by histology, showing decreased skin thickness accompanied by significantly reduced infiltrations of CD4+ and CD8+ lymphocytes but also mast cells. Additionally, early allergen-specific IgE and IgG1 responses were reduced (day 21/35), whereas IgG2a levels remained unchanged. In conclusion, our results demonstrate that PPARgamma-ligand treatment inhibits not only systemic allergic immune response, but also local allergen-mediated dermatitis. Our findings point to therapeutic strategies, including a PPARgamma-ligand-based treatment.

The Tec Family Kinase, IL-2-Inducible T Cell Kinase, Differentially Controls Mast Cell Responses

The Tec family tyrosine kinase, IL-2-inducible T cell kinase (Itk), is expressed in T cells and mast cells. Mice lacking Itk exhibit impaired Th2 cytokine secretion; however, they have increased circulating serum IgE, but exhibit few immunological symptoms of allergic airway responses. We have examined the role of Itk in mast cell function and FcepsilonRI signaling. We report in this study that Itk null mice have reduced allergen/IgE-induced histamine release, as well as early airway hyperresponsiveness in vivo. This is due to the increased levels of IgE in the serum of these mice, because the transfer of Itk null bone marrow-derived cultured mast cells into mast cell-deficient W/W(v) animals is able to fully rescue histamine release in the W/W(v) mice. Further analysis of Itk null bone marrow-derived cultured mast cells in vitro revealed that whereas they have normal degranulation responses, they secrete elevated levels of cytokines, including IL-13 and TNF-alpha, particularly in response to unliganded IgE. Analysis of biochemical events downstream of the FcepsilonRI revealed little difference in overall tyrosine phosphorylation of specific substrates or calcium responses; however, these cells express elevated levels of NFAT, which was largely nuclear. Our results suggest that the reduced mast cell response in vivo in Itk null mice is due to elevated levels of IgE in these mice. Our results also suggest that Itk differentially modulates mast cell degranulation and cytokine production in part by regulating expression and activation of NFAT proteins in these cells.

Stachybotrys chartarum, Trichothecene Mycotoxins, and Damp Building–Related Illness: New Insights into a Public Health Enigma

Damp building-related illnesses (DBRI) include a myriad of respiratory, immunologic, and neurologic symptoms that are sometimes etiologically linked to aberrant indoor growth of the toxic black mold, Stachybotrys chartarum. Although supportive evidence for such linkages is limited, there are exciting new findings about this enigmatic organism relative to its environmental dissemination, novel bioactive components, unique cellular targets, and molecular mechanisms of action which provide insight into the S. chartarum's potential to evoke allergic sensitization, inflammation, and cytotoxicity in the upper and lower respiratory tracts. Macrocyclic trichothecene mycotoxins, produced by one chemotype of this fungus, are potent translational inhibitors and stress kinase activators that appear to be a critical underlying cause for a number of adverse effects. Notably, these toxins form covalent protein adducts in vitro and in vivo and, furthermore, cause neurotoxicity and inflammation in the nose and brain of the mouse. A second S. chartarum chemotype has recently been shown to produce atranones-mycotoxins that can induce pulmonary inflammation. Other biologically active products of this fungus that might contribute to pathophysiologic effects include proteinases, hemolysins, beta-glucan, and spirocyclic drimanes. Solving the enigma of whether Stachybotrys inhalation indeed contributes to DBRI will require studies of the pathophysiologic effects of low dose chronic exposure to well-characterized, standardized preparations of S. chartarum spores and mycelial fragments, and, coexposures with other environmental cofactors. Such studies must be linked to improved assessments of human exposure to this fungus and its bioactive constituents in indoor air using both state-of-the-art sampling/analytical methods and relevant biomarkers.

Detection of ATM Gene Mutations in Young Lung Cancer Patients: A Population-based Control Study

Ataxia-telangiectasia (A-T) is an autosomal recessive disease characterized by neurological and immunological symptoms, radiosensitivity, and cancer predisposition. Heterozygous carriers of risk mutations in the A-T gene are predisposed to epithelial cancers. We initiated a study to elucidate the frequency and clinical relevance of ATM gene mutations in lung cancer patients of the young (LUCY) and compared the results with population-based control subjects from southwest Germany (KORA=Cooperative Health Research in the Region of Augsburg). In this study, the clinical relevance of ATM gene mutations (S707P; 1066-6T-->G; 2250G-->A, 7630A-->C, E1978X, R2443X, 3801delG, S49C, and D2625E&A2626P, L1420F, P1045R) in 183 young lung cancer patients (<50 years) is evaluated. The control population was comprised of 200 cancer-free subjects from the KORA study. A total of 25 heterozygous carriers of ATM in the LUCY, respectively; 32 heterozygotes in the KORA group were identified. The observed allele frequencies in the LUCY cases were within the range detected for the control subjects (KORA). Multiple analyses of lung cancer patients who carried at least one risk allele of the ATM did not show significantly elevated or reduced risks. In this study, 16% of the German control subjects had ATM variants. ATM variants were detected in about 14% of the lung cancer patients and did not differ significantly from the control subjects. In comparison to young lung cancer patients, ATM gene mutations had no detectable relevant modifying effect on lung cancer risk.

Anti-CD20-Therapie zur Remissionsinduktion und -erhaltung bei therapierefraktärem systemischen Lupus erythematodes

We present nine cases of systemic lupus erythematosus with refractory disease that we treated with the chimeric monoclonal anti-CD20 antibody rituximab. Three patients had renal disease, three neurological involvement with transverse myelitis and vasculitis of the central nervous system, one thrombocytopenia, one skin involvement with generalized erythema and one patient had constitutional, haematological and immunological symptoms. Two patients with renal disease, the patient with immune thrombocytopenia and the three patients with neurological disease, who stayed in remission despite a reduction of immunosuppressive therapy, responded particularly well to the therapy. Five of nine patients showed an improvement in ECLAM of at least two points. During therapy only minor adverse events were observed. One patient died during follow-up which was unrelated to the therapy. The selective depletion of B-lymphocytes in the therapy of systemic lupus erythematosus seems to be an effective and safe treatment option for different manifestations.

Ataxia-Telangiectasia in Iran: Clinical and Laboratory Features of 104 Patients

Ataxia-telangiectasia is a multisystem disorder characterized by progressive neurologic impairment, variable immunodeficiency, impaired organ maturation, x-ray hypersensitivity, oculocutaneous telangiectasia, and a predisposition to malignancy. To evaluate clinical and immunologic features of Iranian patients with ataxia-telangiectasia, the records of 104 patients with ataxia-telangiectasia (54 male, 50 female) with the age range of 1.6-23.5 years were reviewed. The Iranian Primary Immunodeficiency Registry was used as the data source. Progressive ataxia was seen in all the patients. Other symptoms were eye movement disorders (n = 84), slurred speech (n = 70), mental retardation (n = 10), and ocular (n = 87) and cutaneous (n = 73) telangiectasia. Three patients developed leukemia and lymphoma, and 17 patients had family history of malignancy. Positive correlation was seen between clinical immunologic symptoms and immunoglobulin deficiencies (P = 0.004). The predominant infections were sinopulmonary and acute and recurrent infections (78 cases). Infections included pneumonia (56 patients), otitis media (34 patients), and sinusitis (50 patients). Average serum alpha-fetoprotein level was 149 +/- 137 ng/dL. The incidence of ataxia-telangiectasia in Iran is high, possibly due to familial marriages. Treatment should be focused on supportive management to prolong survival.

ATM gene mutations in former uranium miners of SDAG Wismut: A pilot study

Ataxia-telangiectasia is an autosomal recessive disease characterized by neurological and immunological symptoms, radiosensitivity and cancer predisposition. Heterozygous carriers of an ataxia-telangiectasia gene mutation are predisposed to epithelial cancers. We initiated a study to elucidate the frequency and clinical relevance of ATM gene mutations in former uranium miners exposed to high levels of radiation from radon and its decay products. Former uranium miners with Schneeberg lung cancer (n=48), former uranium miners suffering from silicosis (n=60) and uranium miners without occupational lung disorders (n=102) were investigated for nine mutations in the ATM gene. One gastric and one prostate cancer occurred in the group of miners without occupational lung diseases. Mutation analyses for S707P, IVS10-6Tright curved arrow G, 2250Gright curved arrow A, E1978X, R2443X, 3801delG, S49C and D2625E-A2626P were performed using genomic DNA obtained from peripheral blood samples. Three ATM gene alterations (S707P, S49C or IVS10-6Tright curved arrow G) were observed. Of all cancer patients, 8.0% were heterozygous, but only 1.9% of the non-cancer controls were [OR=4.6; 95% confidence interval (CI), 0.8-26.8]. In this pilot study a major role of six ATM gene mutations could not be revealed for cancer predisposition in former uranium miners. The results leave the possibility of a moderate risk associated with more subtle ATM gene alterations.

Systemic Tacrolimus in the Treatment of Severe Atopic Keratoconjunctivitis

Severe atopic keratoconjunctivitis (AKC) forms part of the spectrum of allergic eye disease and is often refractory to conventional topical treatment. Topical cyclosporin A and tacrolimus have been shown to reduce immunologic activation, symptoms, and signs of patients suffering from AKC, but there are no reports on safety and efficacy of systemic tacrolimus for this condition. We report on a retrospective study of 3 patients with severe AKC, where the disease did not respond to conventional therapy, and they were therefore treated with low-dose systemic tacrolimus for at least 1 year as an adjunct to their existing treatment. There was a good clinical response in all patients to low-dose systemic tacrolimus, with a low incidence of side effects and no relapse of symptoms after discontinuation of treatment. Low-dose systemic tacrolimus is a safe and effective treatment of some patients with severe AKC, which is refractory to conventional treatment. Such patients need careful monitoring for side effects, and the long-term benefits need to be assessed as part of a clinical trial.

Parental Perceptions and Use of Complementary and Alternative Medicine Practices for Children with Autistic Spectrum Disorders in Private Practice

The prevalence of autistic spectrum disorder (ASD) in the United States is approximately 1 in 150 children. Many health care providers are unaware of parental beliefs and treatments, both medical and complementary, that parents use for their child with ASD. Understanding these beliefs and practices concerning diagnosis, cause, and utilization of medical and complementary care may help physicians provide better comprehensive care. Parents of children with ASD from 2 private practices-one in New York and one in New Jersey-were mailed a 6-page, self-administered survey. In addition to demographics and ASD type, the survey asked parents who diagnosed their child and if there was a perceived delay in that diagnosis; whether they believed there was any causal reason for their child's autism; what chronic symptoms, if any, their child experiences; and, if they had used any complementary and/or alternative therapies and at whose recommendation. Respondents included 77 of the 150 parents (51%) contacted. Most children were diagnosed by a neurologist and/or developmental pediatrician (54% and 47%, respectively). Average perceived delay in diagnosis was 18 months. Parents most frequently cited immunizations (54%), genetic predisposition (53%), and environmental exposure (38%) as a cause of their child's autism. Approximately half of children were reported as having at least one gastrointestinal, neurological, and/or allergic symptom; more than a third had immunological symptoms. Almost all parents (95%) indicated some use of complementary and alternative medicine (CAM) therapies, with most of the self-reported referrals generated from a physician or nurse (44%). Systemic complaints, parental beliefs, and use of CAM practices warrant open discussion by all health care professionals who provide care to this population.

Genetics of susceptibility to leishmaniasis in mice: four novel loci and functional heterogeneity of gene effects

Symptoms of human leishmaniasis range from subclinical to extensive systemic disease with splenomegaly, hepatomegaly, skin lesions, anemia and hyperglobulinemia, but the basis of this variation is unknown. Association of progression of the disease with Th2 lymphocyte response was reported in mice but not in humans. As most genetic studies in Leishmania major (L. major)-infected mice were restricted to skin lesions, we analyzed the symptomatology of leishmaniasis in mice by monitoring skin lesions, hepatomegaly, splenomegaly and seven immunological parameters. We detected and mapped 17 Leishmania major response (Lmr) gene loci that control the symptoms of infection. Surprisingly, the individual Lmr loci control 13 different combinations of pathological and immunological symptoms. Seven loci control both pathological and immunological parameters, 10 influence immunological parameters only. Moreover, the genetics of clinical symptoms is also very heterogeneous: loci Lmr13 and Lmr4 determine skin lesions only, Lmr5 and Lmr10 skin lesions and splenomegaly, Lmr14 and Lmr3 splenomegaly and hepatomegaly, Lmr3 (weakly) skin lesions, and Lmr15 hepatomegaly only. Only two immunological parameters, IgE and interferon-gamma serum levels, correlate partly with clinical manifestations. These findings extend the paradigm for the genetics of host response to infection to include numerous genes, each controlling a different set of organ-specific and systemic effects.

Pediatric Heart Transplantation across ABO Blood Type Barriers: A Case Study

Heart transplantation with ABO blood type-incompatible donors has historically been contraindicated because of the high risk of an immediate hyperacute humoral graft rejection. The immature neonatal immune system presents an immunologic window that allows for breaching the ABO barrier before the natural development of anti-ABO antibodies. Information from a small series of neonates has demonstrated similar survival rates and posttransplant outcomes compared to ABO-compatible transplantations. In the posttransplant period, particular attention is placed on the surveillance of graft-specific antibody production and monitoring for immunologic signs and symptoms of early graft vasculopathy. This article presents a case study of a neonate with congenital heart disease who underwent one of the first successful ABO-incompatible heart transplantations in the United States.

Pediatric heart transplantation across ABO blood type barriers: a case study

Heart transplantation with ABO blood type-incompatible donors has historically been contraindicated because of the high risk of an immediate hyperacute humoral graft rejection. The immature neonatal immune system presents an immunologic window that allows for breaching the ABO barrier before the natural development of anti-ABO antibodies. Information from a small series of neonates has demonstrated similar survival rates and posttransplant outcomes compared to ABO-compatible transplantations. In the posttransplant period, particular attention is placed on the surveillance of graft-specific antibody production and monitoring for immunologic signs and symptoms of early graft vasculopathy. This article presents a case study of a neonate with congenital heart disease who underwent one of the first successful ABO-incompatible heart transplantations in the United States.

Incidence of occupational rhinoconjunctivitis and risk factors in animal-health apprentices

Background Exposure to laboratory animals often causes the appearance of immunologic sensitization and symptoms. Objective Our aim was to determine the incidence of occupational rhinoconjunctivitis and the timing of symptoms and their determinants in apprentices starting exposure to laboratory animals. Methods Data from 387 (92.8%) of 417 students entering career programs in animal health in 5 schools were kept for analysis. Questionnaires and skin prick tests with common and occupational inhalants were carried out on entry and at follow-up visits scheduled at 8, 20, 32, and 44 months, depending on the schools. Responsiveness to inhaled methacholine was assessed at entry. Results Ninety-three (24%) subjects showed incident occupational rhinoconjunctivitis symptoms, and 37 (9.6%) had symptoms combined with skin sensitization to an animal-derived allergen. Symptoms such as sneezing, rhinorrhea, and itchy eyes tended to develop early in the course of exposure. In two thirds of the subjects, symptoms persisted at subsequent visits. In a multivariate analysis the determinants of the appearance of rhinoconjunctivitis with or without allergic sensitization included sensitization to grass pollens (odds ratio [OR], 1.78; 95% CI, 0.99-3.19), as well as nasal (rhinorrhea in contact with dust: OR, 1.79; 95% CI, 1.05-3.05) and bronchial symptoms (chest tightness: OR, 3.31; 95% CI, 0.98-11.25; cough on exposure to strong odors: OR, 1.88; 95% CI, 0.98-3.59). Conclusion The incidence of occupational rhinoconjunctivitis symptoms with or without immunologic sensitization is high in apprentices starting exposure to laboratory animals. Symptoms related to histamine release are common in the early course of exposure. Determinants include immunologic and target-organ susceptibility.

The ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency disease

Only one human disease that involves Mendelian inheritance of immunodeficiency and aberrant DNA methylation has been identified. This is a rare chromosome breakage disease called the immunodeficiency, centromeric region instability, and facial anomalies syndrome (ICF). Its diagnostic characteristics are agammaglobulinemia with B cells as well as DNA rearrangements targeted to the centromere-adjacent heterochromatic region (qh) of chromosomes 1, 16, and sometimes 9 in mitogen-stimulated lymphocytes. These rearrangement-prone regions show DNA hypomethylation in all examined ICF cell populations. This review summarizes our knowledge about the immunological symptoms of ICF; the nature of DNMT3B mutations in ICF patients; the phenotypes of DNA hypomethylation mutants in humans, mice, and Arabidopsis; the epigenetics of ICF; and ICF-specific RNA expression and cell-surface antigen expression in lymphoblastoid cell lines. Comparisons of ICF and control lymphoblastoid cell lines and ICF patients' symptoms suggest an involvement of DNA methylation in the late stages of lymphocyte maturation.

Peroxisome proliferator-activated receptor γ ligands attenuate immunological symptoms of experimental allergic asthma

Asthma is characterized by a predominant T H2 type immune response to airborne allergens. Controlling T H2 cell function has been proposed as therapy for this disease. We show here that ligands for the nuclear receptor peroxisome proliferator activated receptor (PPAR)γ significantly reduced the immunological symptoms of allergic asthma in a murine model of this disease. A PPARγ ligand, 15-deoxy-delta(12,14)-prostaglandin J(2), significantly inhibited production of the T H2 type cytokine IL-5 from T cells activated in vitro. More importantly, in a murine model of allergic asthma, mice treated orally with ciglitazone, a potent synthetic PPARγ ligand, had significantly reduced lung inflammation and mucous production following induction of allergic asthma. T cells from these ciglitazone treated mice also produced less IFNγ, IL-4, and IL-2 upon rechallenge in vitro with the model allergen. Our results suggest that ligands for PPARγ may be effective treatments for asthmatic patients.