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Immune-mediated Diseases (immune-mediated + disease)
Selected AbstractsA role for innate immunity in type 1 diabetes?DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2003H. Beyan Abstract Two arms of the immune system, innate and adaptive immunity, differ in their mode of immune recognition. The innate immune system recognizes a few highly conserved structures on a broad range of microorganisms. On the other hand, recognition of self or autoreactivity is generally confined to the adaptive immune response. Whilst autoimmune features are relatively common, they should be distinguished from autoimmune disease that is infrequent. Type 1 diabetes is an immune-mediated disease due to the destruction of insulin secreting cells mediated by aggressive immune responses, including activation of the adaptive immune system following genetic and environmental interaction. Hypotheses for the cause of the immune dysfunction leading to type 1 diabetes include self-reactive T-cell clones that (1) escape deletion in the thymus, (2) escape from peripheral tolerance or (3) escape from homeostatic control with an alteration in the immune balance leading to autoimmunity. Evidence, outlined in this review, raises the possibility that changes in the innate immune system could lead to autoimmunity, by either priming or promoting aggressive adaptive immune responses. Hostile microorganisms are identified by genetically determined surface receptors on innate effector cells, thereby promoting clearance of these invaders. These innate effectors include a few relatively inflexible cell populations such as monocytes/macrophages, dendritic cells (DC), natural killer (NK) cells, natural killer T (NKT) cells and ,, T cells. Recent studies have identified abnormalities in some of these cells both in patients with type 1 diabetes and in those at risk of the disease. However, it remains unclear whether these abnormalities in innate effector cells predispose to autoimmune disease. If they were to do so, then modulation of the innate immune system could be of therapeutic value in preventing immune-mediated diseases such as type 1 diabetes. Copyright © 2002 John Wiley & Sons, Ltd. [source] A case of suspected contact dermatitis in a juvenile cynomolgus monkey (Macaca fascicularis)JOURNAL OF MEDICAL PRIMATOLOGY, Issue 2008Joanne Morris Abstract Background, A 2-year-old male cynomolgus monkey (Macaca fascicularis) presented with vesicular dermatitis exhibiting freshly ruptured blisters, crusts, and papules on the extremities and face. Methods, Complete blood count, serum chemistry, skin biopsy, skin scrape, and culture of a fresh blister were initially submitted for diagnostics. Results, Skin biopsy of the affected area revealed a non-suppurative eosinophilic dermatitis with mild thickening of the epidermis. Serum chemistry showed a marked eosinophilia (1.74 × 103/,l, 17.4%). All other results were within normal limits. Initial differentials included contact dermatitis, immune-mediated disease such as pemphigus or psoriasis. Repeated blood work and skin biopsies were collected as well as serum for allergen-specific IgE latex and food allergy testing. Herpes B virus was added to the differential list after an oral lesion was noted upon repeated physical examination and samples were collected for testing. Repeat blood work maintained a marked eosinophilia and food allergy testing was within normal limits. Serum IgE for latex was equivocal and a follow-up latex sensitivity test was performed and was within normal limits. Repeated skin biopsies were consistent with acute eosinophilic spongiotic dermatitis with vesicles most likely due to contact dermatitis. No therapy was initiated during the diagnostic period and no etiology was confirmed. Conclusions, Over time the dermatitis and eosinophilia resolved spontaneously. The animal is currently free of any lesions and maintains an eosinophil count within normal limits. [source] Retrospective study of fever in dogs: laboratory testing, diagnoses and influence of prior treatmentJOURNAL OF SMALL ANIMAL PRACTICE, Issue 7 2006I. A. Battersby Objectives: To analyse the demographic information of dogs referred for investigation of fever, to determine the usefulness of various diagnostic investigations and to assess the effect of treatment before referral on the presence of fever at referral, the duration of the investigation and the ability to reach a final diagnosis. Methods: The clinical records of 66 dogs, in which fever was part of the clinical signs documented by the referring veterinary surgeon, were reviewed. The effects of treatment 24 hours before referral on temperature at initial consultation and on time to diagnosis were evaluated. The effect of body temperature at initial consultation on cost and on time to diagnosis was also determined. The effect of insurance on costs incurred was assessed. The utility of different diagnostic investigations was recorded, and cases were classified according to the final diagnosis. Results: Only 34·8 per cent of dogs were diagnosed with immune-mediated disease, with most frequent diagnoses being steroid-responsive meningitis and polyarthritis. Treatment 24 hours before referral significantly increased the time to diagnosis (P=0·004) and affected the presence of fever at referral (P=0·006). Insurance status did not significantly affect cost incurred by the owner. Clinical Significance: This study documents a high incidence of immune-mediated disease in dogs referred for investigation of fever. It also documents a higher incidence of inflammatory central nervous system disease in febrile dogs than that reported previously. Of the diagnostic modalities employed in the majority of cases, radiography, cytology and bacteriological and fungal cultures (fluids/tissues) were the most useful. It is suggested that treatment is withdrawn or withheld before commencing diagnostic investigation of fever. [source] Chimerism occurs twice as often in lupus nephritis as in normal kidneysARTHRITIS & RHEUMATISM, Issue 9 2006Idske C. L. Kremer Hovinga Objective Systemic lupus erythematosus (SLE) is an immune-mediated disease that particularly affects the kidneys, causing lupus nephritis. In experimental mouse models, lupus nephritis can be mimicked by inducing a chimeric state through the injection of parental T cells in offspring. In humans, pregnancy-induced chimerism may play a role in the pathogenesis of autoimmune diseases such as SLE, but it is likely that only certain chimeric cells have pathogenic potential. In this study, we investigated whether the distribution of chimeric cells is different in the kidneys of women with SLE from that in normal kidneys, and we examined the phenotype of chimeric cells in women with SLE. Methods The presence of chimeric cells was investigated by in situ hybridization targeting the Y chromosome in 57 renal biopsy samples from 49 women with lupus nephritis. Fifty-one kidney autopsy specimens without histomorphologic lesions served as controls. Double-staining for the Y chromosome in combination with CD3 and CD34 markers was performed in 5 kidney specimens with lupus nephritis to identify the phenotype of the chimeric cells. Results Y chromosome,positive cells were found in 27 of 49 patients with lupus nephritis and in 13 of 51 normal controls (P < 0.01). Both CD3+ and CD34+ chimeric cells were identified in lupus nephritis kidney specimens. Conclusion Chimeric cells are present significantly more often in kidneys with lupus nephritis than in normal kidneys, and some of these chimeric cells are T cells. This finding is interesting in light of experimental models demonstrating that lupus nephritis is initiated by chimeric T cells. [source] Clinical Immunology Review Series: An approach to the patient with recurrent superficial abscessesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2008S. L. Johnston Summary Patients may be referred to the immunology clinic for investigation of recurrent superficial abscess formation. In the majority of adult patients this clinical presentation does not equate with an underlying primary immune deficiency. Nevertheless, recurrent mucocutaneous abscesses can be associated with significant morbidity and long-term complications, including scarring and fistula formation, and may be associated with underlying immune-mediated disease. This review sets out an approach to the patient with recurrent superficial abscesses, focusing on the differential diagnoses, investigation and management of both the common causes and those associated with specific immune deficiency. [source] Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeuticsIMMUNOLOGICAL REVIEWS, Issue 1 2008Marc Feldmann Summary: Advances in cDNA and monoclonal antibody technology in the 1980s fuelled the discovery and characterization of the properties of cytokines. It became apparent that because cytokines were expressed in tissues derived from autoimmune diseases, they were likely to be of fundamental importance in disease pathogenesis and developing a new class of biological therapeutics. In this review, we describe the history of bench to bedside translation of work that led to the identification of tumor necrosis factor (TNF) as a key regulator of the loss of homeostatic immune-inflammatory responses in rheumatoid arthritis (RA) and a good therapeutic target. First in human clinical trials in collaboration with a biotechnology company, the safety and efficacy of TNF blockade with a chimeric monoclonal antibody was substantiated in patients refractory to standard anti-rheumatoid drugs. Abnormal immune-inflammatory responses after therapy showed improvement and remain a focus of ongoing research in many laboratories. Longer term multi-center studies that followed with several anti-TNF biologicals have demonstrated the augmented efficacy, including inducing clinical remission, of low dose methotrexate and anti-TNF therapy co-therapy, but serious infections and lymphomas in a low frequency have been observed. In the course of the past decades, three ,blockbuster' anti-TNF biologicals are in the clinic. Over a million patients with RA and other immune-mediated diseases have been successfully treated, and a better perspective on the risk of harm and its management has become part of good clinical practice. This success has encouraged a burgeoning industry of biologicals for chronic diseases. [source] Analysis of the CC chemokine receptor 5 (CCR5) ,32 polymorphism in Behçet's diseaseINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2004X. Yang Summary Chemokines are important determinants of the early inflammatory response. The CC chemokine receptor 5 (CCR5) ,32 variant results in a non-functional form of the chemokine receptor, and has been implicated in a variety of immune-mediated diseases. To investigate its role in the pathogenesis of Behçet's disease, we studied 350 patients and 519 healthy controls from three ethnic groups. While significant inter-ethnic variation in allele frequency was observed, no association was identified with disease, even when data were stratified by the known susceptibility gene HLA-B*51. [source] Anti-Erythrocyte Antibodies and Disease Associations in Anemic and Nonanemic DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2008P. Morley Background: Flow cytometry has been used to detect anti-red blood cell (RBC) antibodies in dogs with immune-mediated hemolytic anemia (IMHA), but the prevalence of anti-RBC antibodies in anemic and nonanemic dogs with a variety of different diseases has not been assessed previously. Hypothesis: We hypothesized that anti-RBC antibodies would be more common in anemic dogs and in dogs with immune-mediated disorders and cancer. Animals: Blood samples from 292 dogs were analyzed prospectively by flow cytometry for anti-RBC antibodies. Methods: Blood samples from 147 anemic and 145 nonanemic dogs were evaluated by flow cytometry to detect surface-bound immunoglobulin (Ig) G and IgM antibodies on RBC. Disease associations with RBC antibodies were determined, as was the correlation between disease status and the percentage of Ig+ RBC. The specificity and sensitivity of flow cytometry and clinical variables for the diagnosis of IMHA were compared by Bayesian analysis. Results: Anemic dogs were significantly more likely to be positive for anti-RBC antibodies (IgG, IgM, or both) than nonanemic dogs. Anemic dogs also had significantly higher percentages of Ig+ RBC than nonanemic dogs, whereas dogs with IMHA had significantly higher percentages of Ig+ RBC than dogs with all other diseases. Dogs with IMHA, infectious diseases, and immune-mediated thrombocytopenia were significantly more likely to have anti-RBC antibodies than dogs with other medical or surgical diseases. Conclusions: Anemic dogs with immune-mediated diseases and infectious diseases were at the highest risk for the development of anti-RBC antibodies, and flow cytometry for the detection of IgG on RBC was highly sensitive and specific for the diagnosis of IMHA. [source] Effects of feeding probiotics during weaning on infections and antibody responses to diphtheria, tetanus and Hib vaccinesPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1 2008Christina E. West Microbial exposure is necessary for the development of normal immune function, which has driven the idea of using probiotics for treatment and prevention of immune-mediated diseases in infancy and childhood. Mounting evidence indicates that probiotics have immunomodulatory effects. However, the mechanisms are still poorly understood. Specific antibody response is a valuable proxy for immune system maturation status in infancy. We aimed at determining the impact of Lactobacillus F19 (LF19) during weaning on infections and IgG antibody responses to routine vaccines. In a double-blind, placebo-controlled randomized intervention trial, infants were fed cereals with (n = 89) or without LF19 (n = 90) from 4 to 13 months of age. Infants were immunized with DTaP (diphtheria and tetanus toxoid and acellular pertussis), polio and Hib-conjugate vaccines at (3), 5 and 12 months of age. We assessed the number of days with infections, antibiotic prescriptions and antibody concentrations to Hib capsular polysaccharide (HibPS), diphtheria toxin (D) and tetanus toxoid (T) before and after the second and third doses. Days with infectious symptoms did not differ between the groups. Days with antibiotic prescriptions were fewer in the LF19 group (p = 0.044). LF19 enhanced anti-D concentrations when adjusting for breastfeeding duration and colonization with LF19 (p = 0.024). There was an interaction of the intervention and colonization with LF19 on anti-T concentrations during the course of vaccination (p = 0.035). The anti-HibPS concentrations were higher after the first and second dose of Hib vaccine in infants breastfed <6 months compared with those breastfed ,6 months (p < 0.05), with no effect by LF19. In conclusion, feeding LF19 did not prevent infections, but increased the capacity to raise immune responses to protein antigens, with more pronounced effects in infants breastfed <6 months. [source] Is affluence a risk factor for bronchial asthma and type 1 diabetes?PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 7 2006Alberto Tedeschi In the last decades, an increase in bronchial asthma and type 1 diabetes occurrence has been observed in affluent countries, and a positive association between the two disorders has been demonstrated at the population level. This association could be explained by common risk factors predisposing to both disorders. Altered environmental and lifestyle conditions, possibly related to socio-economic status, might account for the rising trend of the two disorders. To test this hypothesis, we calculated the correlation between the occurrence of type 1 diabetes and asthma, the gross national product (GNP) and the infant mortality rate, in several European and extra-European countries. GNP was positively correlated with the incidence of type 1 diabetes and with symptoms of asthma in European (rsp: 0.53 and 0.69; p = 0.001 and p < 0.0001, respectively) and extra-European countries (rsp: 0.44 and 0.46; p = 0.04 for both diseases). Infant mortality rate was inversely correlated with GNP and with the occurrences of the two diseases in Europe (rsp: ,0.66, p < 0.0001 for type 1 diabetes; rsp:, 0.51, p = 0.01 for asthma). In extra-European countries, a significant relationship was found between infant mortality and asthma (rsp: ,0.46; p = 0.03); a trend towards a negative correlation between infant mortality and type 1 diabetes was also found, although no statistical significance was reached (rsp: ,0.21; p = 0.31). This analysis indicates that type 1 diabetes and asthma are positively associated with the GNP at the population level. Similarly, countries with low infant mortality rates tend to have a higher incidence of these immune-mediated diseases. Although GNP reflects many societal and lifestyle differences, it is notable that a high socio-economic status implies a reduced or delayed exposure to infectious agents. The reduced pressure of infectious agents on the immune system throughout life might contribute to increase the susceptibility to bronchial asthma and type 1 diabetes. [source] Inhibitory effect of pooled human immunoglobulin on cytokine production in peripheral blood mononuclear cellsPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1 2006Kuan-Hsun Wu Human intravenous immunoglobulins (IVIG) are widely used as immunomodulators because of their ability to modify the course of various immune-mediated diseases. We investigated the mechanisms responsible for the regulatory effects of IVIG on in vitro human peripheral blood mononuclear cell (PBMC) cytokine production. Pre-incubation of PBMCs with IVIG inhibited lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA)/ionomycin stimulated cytokine secretion. Pre-incubation of PBMCs with IVIG induced a significant inhibition of LPS-stimulated (IL-6) secretion (p = 0.045); the effect on tumor necrosis factor- , (TNF- ,) secretion was not significant (p = 0.234). Pre-incubation of PBMCs with IVIG inhibited IL-6 secretion (p = 0.033) stimulated with anti-CD14 antibody cross-linking but had no significant effect on TNF- , secretion (p = 0.125). PBMC pre-incubation with anti-CD14-blocking antibody induced a significant reduction (p = 0.042) in LPS-stimulated TNF- , secretion in comparison with a non-significant reduction (p =0.256) noted with IVIG pre-treatment. In contrast, pre-incubation of PBMCs with anti-CD14 antibody did not induce a significant reduction in LPS-stimulated IL-6 secretion (p = 0.166) in comparison with a significant reduction (p = 0.001) induced with IVIG pre-treatment. Our data suggest that the immunoregulatory properties of IVIG may rely on several mechanisms, some of which may be independent of CD14. Our data also showed that cross-linking cell membrane-bound IVIG with anti-human kappa- and lambda-chain antibodies resulted in cytokine secretion levels similar to those elicited by LPS. In addition, intracellular DNA staining results did not support the involvement of apoptosis in the regulatory mechanisms of IVIG. This data may further our understanding of the immunoregulatory effects exerted by IVIG on the production of inflammatory-response mediators. [source] Fatal case of bilateral internal jugular vein thrombosis following IVIg infusion in an adolescent girl treated for ITPAMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2008Pui-Ying Iroh Tam Intravenous immunoglobulin (IVIg) is often used as therapy in immune-mediated diseases and is generally considered a safe therapeutic agent. However, thrombotic complications such as myocardial infarction and deep vein thrombosis have been reported, although primarily in older adults. We describe a 13-year-old girl who received one dose of IVIg for immune thrombocytopenic purpura and developed fatal bilateral jugular venous thromboses. This is the first known case of IVIg-associated thrombosis in an adolescent and alsothe first report describing internal jugular vein thrombosis associated with IVIg infusion. We identify additional risks that may potentiate the agent's thrombotic risk. Am. J. Hematol., 2008. © 2007 Wiley-Liss, Inc. [source] Interferon-,,dependent inhibition of B cell activation by bone marrow,derived mesenchymal stem cells in a murine model of systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 9 2010Francesca Schena Objective Bone marrow,derived mesenchymal stem cells (BM-MSCs) are multipotent cells characterized by immunomodulatory properties and are therefore considered a promising tool for the treatment of immune-mediated diseases. This study was undertaken to assess the influence of murine BM-MSCs on the activation of B cells in (NZB × NZW)F1 mice as an animal model of systemic lupus erythematosus (SLE). Methods We evaluated the in vitro effects of BM-MSCs on the proliferation and differentiation to plasma cells of splenic mature B cell subsets, namely follicular and marginal zone B cells isolated from (NZB × NZW)F1 mice. Lupus mice were also treated with BM-MSCs, and serum autoantibodies, proteinuria, histologic changes in the kidney, and survival rates were monitored. Results BM-MSCs inhibited antigen-dependent proliferation and differentiation to plasma cells of follicular and marginal zone B cells in vitro. This inhibitory effect was dependent on interferon-, (IFN,) and was mediated by cell-to-cell contact, involving the programmed death 1 (PD-1)/PD ligand pathway. In vivo treatment with BM-MSCs did not affect the levels of anti,double-stranded DNA antibodies or proteinuria. However, a reduction in glomerular immune complex deposition, lymphocytic infiltration, and glomerular proliferation was observed. Conclusion Our findings indicate that BM-MSCs affect B cell receptor,dependent activation of both follicular and marginal zone B cells from lupus mice. This inhibitory effect is IFN,-dependent and cell contact,dependent. MSCs in vivo do not affect the production of autoantibodies, the level of proteinuria, or the mortality rates. Nonetheless, the significant improvement in histologic findings in the kidney supports the potential role of MSCs in the prevention of glomerular damage. [source] Confirmation of an association between rs6822844 at the Il2,Il21 region and multiple autoimmune diseases: Evidence of a general susceptibility locusARTHRITIS & RHEUMATISM, Issue 2 2010Amit K. Maiti Objective Autoimmune diseases often have susceptibility genes in common, indicating similar molecular mechanisms. Increasing evidence suggests that rs6822844 at the IL2,IL21 region is strongly associated with multiple autoimmune diseases in individuals of European descent. This study was undertaken to attempt to replicate the association between rs6822844 and 6 different immune-mediated diseases in non-European populations, and to perform disease-specific and overall meta-analyses using data from previously published studies. Methods We evaluated case,control associations between rs6822844 and celiac disease (CD) in subjects from Argentina; rheumatoid arthritis (RA), type 1 diabetes mellitus (DM), primary Sjögren's syndrome (SS), and systemic lupus erythematosus (SLE) in subjects from Colombia; and Behçet's disease (BD) in subjects from Turkey. Allele and gene distributions were compared between cases and controls. Meta-analyses were performed using data from the present study and previous studies. Results We detected significant associations of rs6822844 with SLE (P = 0.008), type 1 DM (P = 0.014), RA (P = 0.019), and primary SS (P = 0.033) but not with BD (P = 0.34) or CD (P = 0.98). We identified little evidence of population differentiation (FST = 0.01) within cases and controls from Argentina and Colombia, suggesting that association was not influenced by population substructure. Disease-specific meta-analysis indicated significant association for RA (Pmeta = 3.61 × 10,6), inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) (Pmeta = 3.48 × 10,12), type 1 DM (Pmeta = 5.33 × 10,5), and CD (Pmeta = 5.30 × 10,3). Overall meta-analysis across all autoimmune diseases reinforced association with rs6822844 (23 data sets; Pmeta = 2.61 × 10,25, odds ratio 0.73 [95% confidence interval 0.69,0.78]). Conclusion Our results indicate that there is an association between rs6822844 and multiple autoimmune diseases in non-European populations. Meta-analysis results strongly reinforce this robust association across multiple autoimmune diseases in both European-derived and non-European populations. [source] | ||||||||||