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At least 1,531 records · Page 85Linked to original sources
PubMed1998

Rheumatoid arthritis. Early intervention can change outcomes.

Rheumatoid arthritis (RA) is an autoimmune disease with a predilection for synovial tissues, although it can affect other organs. Although the precise etiology is uncertain, viruses, genetics, immune dysfunction and physical trauma have all been implicated as causes for RA. The most basic definition, therefore, is that RA is inflammatory. The RA patient may have difficulty closing a fist or may have a week grip. The late stages of RA are easy to identify by X-ray, but to really perform a service for a patient, you must be able to identify its early stages. To do this, you must be able to examine joints. If a patient does not have a history of liver disease or heavy alcohol intake, methotrexate is the first treatment choice except in the very mildest of cases, when you can use NSAIDs. Steroids are sometimes an essential treatment, but use them with great caution and pay attention to the minimum effective dose.

Arthritis, Rheumatoid↗
PubMed1998

Effects of in utero alcohol exposure on B-cell development in the murine fetal liver.

Fetal alcohol syndrome is one of the leading causes of birth defects in this country. Children exposed to alcohol in utero suffer from growth and mental retardation, physical abnormalities, and immune dysfunction. Previous work from this laboratory demonstrated that B lymphopoiesis is delayed in mice exposed to alcohol in utero. The deficit in B-cell development was apparent shortly after birth and extended to well after weaning. Because lymphopoiesis begins in the fetal liver, the current study was done to determine if fetal B-cell development was affected as well by in utero exposure to alcohol. We now show that the effects of in utero alcohol exposure on B lymphopoiesis do not become apparent until late in gestation. Flow cytometry was used to enumerate several intermediates in the B-cell developmental pathway. These phenotypic analyses showed that before day 17 of gestation, B-lineage intermediates developed normally when compared with control animals. However, between days 17 and 18 of gestation, an abnormality in the population dynamics of B-lineage intermediates became apparent in the fetal liver of alcohol-exposed mice. Early intermediates in the B-cell developmental pathway were present in normal numbers; however, the more mature progenitors as well as B cells were decreased in number by gestational day 18. These data suggest that in utero alcohol exposure disrupts the ability of B-lineage intermediates to progress along the developmental pathway to maturity, thereby leaving the animal immunocompromised at birth.

Animals↗
PubMed1998

Thyroid function and autoimmunity in sarcoidosis: a case-control study.

AIM: To evaluate thyroid function and the presence of antithyroid autoantibodies in patients with sarcoidosis, compared to patients with chronic obstructive pulmonary disease (controls). METHODS: Sera were obtained from 26 patients (19 women and 7 men) with active sarcoidosis, age and sex matched to 26 patients with diagnosed chronic obstructive pulmonary disease. Baseline thyrotropin, total triiodothyronine and thyroxine, antithyroglobulin autoantibodies, and antithyroid peroxidase autoantibodies were analyzed. RESULTS: Only antithyroglobulin autoantibodies were significantly elevated in sarcoidosis patients (p=0.041, Wilcoxon two-sample test). CONCLUSION: Basic thyroid function parameters, with the exception of antithyroglobulin autoantibodies, were within the normal limits in patients with sarcoidosis. Their presence should be interpreted as another characteristic of a generalized immune dysfunction in sarcoidosis. Screening of thyroid disease in patients with sarcoidosis does not seem necessary.

Adult↗
PubMed1998

[Desquamative interstitial pneumonitis accompanied by a variety of autoimmune abnormalities in an individual with a history of asbestos exposure].

A 75-year-old-man who had been occupationally exposed to asbestos over several decades was admitted complaining of dry cough and mild exertional dyspnea. Chest X-ray films revealed the presence of bilateral infiltrates. An open biopsy showed the lung pathology to be desquamative interstitial pneumonitis (DIP), and detected a calcified plaque of the left parietal pleura at cost-phrenic sulcus, which on microscopic inspection demonstrated thin needle-like structures suggestive of asbestos particles. A hormonal examination showed decreased levels of tri-iodothyronine and tetraiodothyronine and an increased level of thyroid stimulating hormone. Additionally, a positive microsome test indicated autoimmune hypothyroidism. A serological study was positive for anti-nuclear antibody and direct Coombs, and showed heightened levels of IgG. The patient was placed on oral prednisolone therapy; one month later, his symptoms had subsided, and his lung function and chest x-ray findings had improved significantly. In addition, the abnormal values for autoimmune and thyroid function eventually returned to normal ranges. These findings suggest that DIP and humoral immune dysfunction were caused by asbestos exposure, and responded well to steroid treatment.

Aged↗
PubMed2004

Potential role of humoral immunity in cardiac dysfunction of patients suffering from dilated cardiomyopathy.

OBJECTIVES: This research was conducted to evaluate the role played by the humoral immune system in cardiac dysfunction among dilated cardiomyopathy (DCM) patients, as enabled by immunoadsorption therapy (IA) that effectively removes functionally active cardiac autoantibodies from plasma. BACKGROUND: Various circulating autoantibodies have been detected among patients suffering from DCM. METHODS: Before IA, antibodies were purified from plasma of 45 DCM patients (left ventricular ejection fraction [LVEF] <30%). We analyzed the functional effects of antibodies (300 mg/l) on calcium transients and on systolic cell shortening in adult rat cardiomyocytes. After this in vitro analysis, IA was performed in four courses at one-month intervals until month 3. RESULTS: Antibodies from 29 patients induced a reduction (>10%) in calcium transients (mean reduction: -16.5 +/- 1.9%) and a simultaneous reduction (>10%) of cell shortening (mean reduction: -21.2 +/- 1.8%) on cardiomyocytes (p < 0.001) (cardiodepressant group). Antibodies from 16 patients did not significantly influence calcium transients and cell shortening (<10%) (non-cardiodepressant group). During the first IA course, the cardiodepressant group demonstrated an acute increase in cardiac index (CI) from 2.2 +/- 0.1 l/min/m(2) to 2.9 +/- 0.1 l/min/m(2) (p < 0.001). In the non-cardiodepressant group, hemodynamics did not significantly change throughout three months. After three months before the final IA course (prolonged effects), the CI was 2.1 +/- 0.1 l/min/m(2) in the non-cardiodepressant group and 2.9 +/- 0.1 l/min/m(2) in the cardiodepressant group (p < 0.001). After three months LVEF increased only in the cardiodepressant group: from 20.8 +/- 1% to 30.5 +/- 1% (p < 0.01). CONCLUSIONS: In the majority of DCM patients, disturbances of humoral immunity with production of cardiodepressant antibodies may play a functional role in cardiac dysfunction. Evidence of cardiodepressant antibodies predicts hemodynamic benefits during IA.

Animals↗
PubMed1983

Anti-islet immunity and thymic dysfunction in the mutant diabetic C57BL/KsJ db/db mouse.

Anti-islet immune reactions were studied in vitro in genetically diabetic homozygote C57BL/KsJ db/db mice, using murine islet cells as a target. Spleen lymphocytes inhibited insulin secretion by the islet cells. This inhibition was abolished when T-cells were eliminated by treatment with anti-Thy 1.2 monoclonal antibody in the presence of complement. Anti-islet complement-dependent antibody (CDA) and antibody-dependent cell cytotoxicity (ADCC) were also found in the sera of these mice. This anti-islet immunity was detectable as early as the tenth day of life and lasted throughout the entire life span of the animals. A significant lymphopenia was detected in thymus and spleen cell populations. None of these anomalies was found in control heterozygote mice. Thymic function was explored in the same mice by evaluating their serum thymic factor (FTS) levels using a rosette assay. The age-dependent decline of FTS levels was significantly accelerated in diabetic mice as compared with heterozygous littermates. Furthermore, FTS inhibitory immunoglobulins were detected in db/db mouse sera, which inactivated in vitro the biologic potency of synthetic FTS. Histologically, the thymus displayed an accelerated involution. It was shown by indirect immunofluorescence using anti-FTS monoclonal antibodies that the number of FTS+ cells was reduced in db/db mouse thymuses. Histologic study of the islets of Langerhans showed early signs of beta-cell hyperactivity and hypertrophy, followed by beta-cell rarefaction and profound dislocation of islet architecture. Insulitis was not detected.

Animals↗
PubMed1999

The interleukin-12-mediated pathway of immune events is dysfunctional in human immunodeficiency virus-infected individuals.

Interleukin-12 (IL-12) is a potentially critical factor in the immune response against human immunodeficiency virus (HIV) because it is important for regulating proliferation and interferon-gamma (IFN-gamma) production by T cells and natural killer (NK) cells, antigen presentation and accessory cell function by macrophages and dendritic cells, and cytolytic activities of cytotoxic T-lymphocyte cells and NK cells, which are all functions known to be dysfunctional in patients with acquired immune deficiency syndrome. Peripheral blood mononuclear cells (PBMC) from HIV-infected patients have been previously shown to be deficient in the ability to produce IL-12 in response to the bacterial pathogen Staphylococcus aureus Cowan. In this study, impaired IL-12 production in cells from PBMC of HIV-infected patients compared with healthy donors was observed across a broad panel of stimuli derived from infectious pathogens with or without priming with cytokines such as IFN-gamma and IL-4, which amplify the IL-12 induction signal. Analysis of p40 and p35 mRNA accumulation showed that reductions in both subunits contribute to the lower IL-12 secretion of cells from HIV-infected individuals. PBMC from HIV-infected donors also failed to upregulate the IL-12 receptor beta2 chain (IL-12Rbeta2) in response to mitogenic stimuli. The expression of the IL-12Rbeta2 gene could, however, be restored by in vitro exposure to rIL-12. Thus, it is possible that a primary IL-12 defect may lead to secondary deficiencies in expression of the genes for IL-12Rbeta2 and IFN-gamma, thus amplifying immune deficiency during HIV infection.

Adult↗
PubMed1992

Immune function and dysfunction. A primer for the radiologist.

Freedom from infection is the result of many tiers of immune defenses that harmoniously interact to rid the body of microorganisms and their products, which are perceived as foreign. The ability to distinguish self from nonself is embodied in lymphocytes, which serve both effector and regulatory functions. Through the elaboration of cytokines and immunoglobulins, lymphocytes recruit nonspecific immune effectors, focus their activity, and modulate the intensity of the immune response. The phylogenetically more primitive complement system serves a similar function. Although congenital defects in immune function occur, by far the most common causes of immunodeficiency are acquired and occur in patients treated for cancer with myelosuppressive, cytolytic drugs and in transplant recipients treated with immunosuppressants. HIV infection and malnutrition are responsible for even larger numbers of immunocompromised patients worldwide. The nature and severity of infections that occur as a result of immunodeficiency vary as a function of the immune effector targeted and the degree to which it is dysfunctional. Granulocytopenia is well tolerated unless the absolute number of circulating cells falls below 500/mm3. Profound granulocytopenia and deficits of neutrophil function are often manifest as bacterial or fungal infections. Complement deficiency predisposes to infection with encapsulated bacteria such as pneumococci, meningococci, and Haemophilus influenzae. T cells play such a central role in the immune response that their derangement is associated with susceptibility to almost any potential pathogen. These patients often succumb to mortal opportunistic infections. Recent advances in hybridoma and recombinant DNA technology have provided us with immunologic reagents that enable us to manipulate the immune response. Anti-CD3 monoclonal antibody has permitted salvage of solid organ transplants in well-defined clinical settings. Monoclonal antibodies against TNF-alpha and lipopolysaccharide may alter the consequences of gram-negative sepsis. Alternatively, recombinant cytokines have been associated with clinically significant tumor regression in selected patients, presumably by enhancing the nascent antitumor immune response. The development of immunologic reagents such as these in concert with our growing understanding of the immune system may translate to improved care for immunocompromised patients.

Humans↗
PubMedDate not supplied

Cryptic dysfunction of cellular immunity in asymptomatic human immunodeficiency virus (HIV) carriers and its actualization by an environmental immunosuppressive factor.

Peripheral blood lymphocytes from 4 asymptomatic HIV-1 carriers with normally retained EBV-specific cytotoxic T-cell activity were exposed to EBV and incubated with 0.2 ng/ml 4-deoxyphorbol ester, an immunosuppressive substance derived from an African plant Euphorbia tirucalli. The regression of EBV-induced B-cell transformation by EBV-specific cytotoxic T-cells was significantly impaired in the presence of a small amount of 4-deoxyphorbol ester, but not so in 5 HIV-1-seronegative healthy counterparts. When the EBV-specific cytotoxic T-cells from the asymptomatic carriers were exposed to 0.2ng/ml 4-deoxyphorbol ester and incubated with 51Cr-labeled autologous EBV-transformed B lymphocytes, the released radioactivity was significantly smaller than that of the healthy counterparts. The results suggest that the cellular immunity of the asymptomatic HIV-1 carriers is cryptically impaired, and the cryptic immunological dysfunction is actualized by exposure to a small amount of the immunosuppressive substance, a dose which does not affect the immunity of uninfected healthy individuals.

Adolescent↗
PubMed1981

Immune-enhanced phagocytic dysfunction in pulmonary macrophages infected with parainfluenza 1 (Sendai) virus.

Cultured alveolar macrophages infected with parainfluenza 1 (Sendai) virus were treated with specific antiviral immune serum and their phagocytic activity for opsonized erythrocytes (EA), Candida krusei, and Staphylococcus epidermidis quantitated. Membrane Fc receptor and candida binding activity were unaffected by the viral infection. In contrast, the virus infection decreased the phagocytic ingestion of EA. The addition of immune serum induced new phagocytic defects in that the treatment of virus-infected macrophages decreased the binding of EA and candida and reduced the ingestion of the yeast and the staphylococci. In addition, treatment with immune serum also enhanced the phagocytic defects induced by the virus infection alone, further reducing the binding and ingestion of EA. Neither virus infection nor treatment with immune serum affected the intracellular killing of S. epidermidis. These data demonstrated that virus infection of alveolar macrophages in vitro induce phagocytic defects that are accentuated by the treatment of the macrophages with antiviral antibody.

Animals↗
PubMedDate not supplied

CD5 B cells in autoimmune and non immune-mediated thyroid dysfunctions.

In a previous study we demonstrated a significant increase of CD5+ B subset in patients with Graves' disease (GD) compared with normal controls. The aim of this study was to compare the percentage of CD5+ B and CD5- B cells in GD with that in different forms of autoimmune and non immune-mediated thyroid diseases. Seventy-two patients were studied: 28 patients with GD, 20 with silent thyroiditis (ST), 12 with Hashimoto's disease (HD), and 12 subjects affected by hyperthyroidism due to toxic adenoma (TA). Eleven out of 28 patients with GD were also evaluated after six months of methimazole treatment. The study was performed by cytometric analysis. In GD the percentage and the absolute number of CD5+ B cells were significantly increased compared with normal controls (42.5 +/- 18.2% versus 19 +/- 6.3%, p < 0.0001; 142 +/- 153.3/cmm versus 46.9 +/- 22/cmm, p < 0.003, respectively. CD5+ B cells tended to normalise after six months of treatment. In ST the percentage of CD5+ B cells was increased (28.6 +/- 10.2%); conversely the absolute number was in the normal range. Patients affected by HD did not show any significant modification in B cells and their subsets in comparison with controls. In TA, CD5+ B were 7.6 /- 4.4% and 14.3 /- 10.9/cmm. Our results demonstrated a marked increase in both percentage and absolute number of CD5+ cells, only in active GD. The expansion of CD5+ B cells could play a role in the immune imbalance present in this disease.

Adenoma↗
PubMed2005

Graft dysfunction and delayed immune reconstitution following haploidentical peripheral blood hematopoietic stem cell transplantation.

For many children with life-threatening hematological diseases, hematopoietic stem cell transplantation (HSCT) is the only curative option. In children lacking a matched related or unrelated donor and with the certainty that, left untreated, death will ensue alternative donors must be sought. Haplo-identical peripheral blood stem cell transplantation (PBSCT) from a healthy parent is a feasible alternative. To reduce the risk of fatal graft-versus-host disease (GvHD) as a complication of transplant across major histocompatibility antigens, intense T-cell depletion is required. Large numbers of purified, cytokine mobilized peripheral stem cells (the so-called mega-dose concept) are required to compensate for the significantly increased risk of either graft failure or early rejection. In our unit, despite this approach, graft dysfunction has, in a significant group of children, proved problematic and, despite salvage attempts at re-transplantation, usually fatal. In children with hematological malignant disease, our overall relapse-free survival is 41%. However, successful transplant outcome has been associated with considerable delays in immune reconstitution that can be implicated in subsequent viral reactivation. We are investigating new strategies to improve the outcome of haplo-identical PBSCT, which may allow us to offer this form of treatment to more children requiring urgent HSCT.

Adolescent↗
PubMedDate not supplied

Immune activation during cerebellar dysfunction following Plasmodium falciparum malaria.

Evidence for immune activation was investigated in 12 patients with a rare syndrome of self-limiting, delayed onset cerebellar dysfunction following an attack of falciparum malaria which occurred 18-26 d previously. Concentrations of tumour necrosis factor, interleukin 6 and interleukin 2 were all significantly higher in serum samples of patients during cerebellar ataxia than in recovery sera and in the sera of 8 patients who did not develop delayed cerebellar dysfunction following an attack of falciparum malaria. Cytokine concentrations in the cerebrospinal fluid were also significantly higher in ataxic patients than in controls. These findings suggest that immunological mechanisms may play a role in delayed cerebellar dysfunction following falciparum malaria.

Adolescent↗
PubMed1991

Macrophage- and astrocyte-derived transforming growth factor beta as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome.

The multifunctional cytokine, transforming growth factor beta (TGF-beta), was identified by immunocytochemistry in the brain tissues of four patients with acquired immune deficiency syndrome (AIDS), but not in control brain tissue. The TGF-beta staining was localized to cells of monocytic lineage as well as astrocytes, especially in areas of brain pathology. In addition, the brain tissues from the AIDS patients contained transcripts for human immunodeficiency virus 1 (HIV-1) by in situ hybridization, suggesting a correlation between the presence of HIV-1 in the brain and the expression of TGF-beta. However, the expression of TGF-beta was not limited to HIV-1-positive cells, raising the possibility of alternative mechanisms for the induction of TGF-beta in these AIDS patients' brains. To investigate these mechanisms, purified human monocytes were infected in vitro with HIV-1 and were shown to secrete increased levels of TGF-beta. In addition, HIV-1-infected monocytes released a factor(s) capable of triggering cultured astrocytes that are not infected with HIV-1 to secrete TGF-beta. The release of TGF-beta, which is an extremely potent chemotactic factor, may contribute to the recruitment of HIV-1-infected monocytic cells, enabling viral spread to and within the central nervous system (CNS). Moreover, TGF-beta augments cytokine production, including cytokines known to be neurotoxic. The identification of TGF-beta within the CNS implicates this cytokine in the immunopathologic processes responsible for AIDS-related CNS dysfunction.

AIDS Dementia Complex↗
PubMed1984

Dysfunction of humoral immunity in anergic surgical patients: absence of anti-tetanus IgG antibody production.

The experiments described have shown that, whereas the injection of tetanus toxoid (tet) into 8 of 12 control individuals resulted in the appearance of specific anti-tet-IgG antibodies in their plasma, immunization of 14 anergic patients did not elicit an antibody response. This observation was extended to an in vitro system, where cells from four control subjects were shown to secrete anti-tet-IgG antibodies in response to polyclonal activators whereas cells from eight anergic patients did not. It is suggested that this failure of humoral immunity could account for the high risk of bacterial infections in anergy.

Adult↗