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PubMedDate not supplied

Predisposing factors to autoimmune disease.

There are many factors that predispose women to autoimmune disease. The protective effect of testosterone during development prevents most males from getting autoimmune disease, although in some instances this protective effect can be bypassed by either genetic anomalies or endocrinopathies. Autoimmunity is defined as the development of symptoms and antibodies referable to one or another autoimmune disease. Some of the factors that predispose young women to autoimmunity also directly involve the endocrine system and indirectly, disorders of gonadal development. Altered sex steroid metabolism is one endogenous factor that predisposes a young woman to autoimmunity. The metabolism of estrone which can be directed to either the 16-or the 2-metabolites by diet, thyroid function, or certain drugs has a major influence on immune function and possibly gonadal pathology. Attempts to shift the metabolism of estrone to the 2-compounds with a variety of agents actually decreases the predisposition to autoimmunity. Other pre-disposing factors are all related to hormone metabolism and include hyperprolactinemia, the use of exogenous estrogenic agents, or compounds that change basic steroid metabolism. Most of these conditions are reversible.

Adolescent↗

PubMedDate not supplied

Anemia of chronic disorders in systemic autoimmune diseases.

BACKGROUND AND OBJECTIVE: Anemia of chronic disorders (ACD) is a mild to moderate anemia characterized by decreased serum iron, decreased total iron-binding capacity and increased iron stores that occurs in a wide variety of diseases including cancer, chronic infections and inflammatory disorders. The reason for this review is two-fold. First, systemic autoimmune diseases are frequently characterized by ACD. Second, advances in our knowledge of the pathophysiology of systemic autoimmune diseases as well as pathogenesis and treatment of ACD have so far been dealt with separately. Consequently, the approach to the evaluation of ACD in systemic autoimmune disorders has usually been either immunology- or hematology-oriented. The aim of this review is to integrate the pertinent information from both these fields in order to arrive at a more complete understanding of a problem common to hematologists and immunologists. INFORMATION SOURCES: The articles reviewed have been published in journals listed in the Science Citation Index and Medline. In addition, the authors have a vast experience in the field of hematology and are actively working in the field of systemic autoimmune disorders. STATE OF ART AND PERSPECTIVES: ACD is a parameter of disease activity in systemic autoimmune diseases. The severe inflammatory stimuli responsible for the pathophysiology of these disorders lead to several systemic changes (referred to as chronic active phase response) through which the organism tries to cope with chronic tissue injuries. These reactions are brought about by inflammation-associated cytokines, like IL-6, IL-1, TNF alpha, TGF beta that regulate hepatic synthesis of acute phase proteins. Many cytokines involved in chronic acute phase response, including IL-1, TNF alpha, TGF beta, have an inhibitory activity on erythroid colony formation in vitro. In addition, circulating TNF alpha is elevated in rheumatoid arthritis (RA), IL-1 beta serum levels are significantly increased in RA with ACD and RA patients treated in vivo with antibodies (Abs) to TNF alpha show disease improvement, including an increase in Hb values. Reduced erythropoietin (EPO) activity, usually the result of reduced production, plays a role in the pathogenesis of ACD observed in systemic autoimmune diseases. Both the production and the action of EPO may fall under the control of IL-1 and IFN-gamma. The most controversial and stimulating aspect of the pathogenesis of ACD in systemic autoimmune disorders is the role of iron metabolism and nitric oxide (NO), which contributes to the regulation of iron cellular metabolism. Both iron deficiency and iron overload may influence the proliferation of B and T lymphocytes and differentially affect T helper (TH)-1 and TH-2 lymphocytes. Furthermore, TH-1 cytokines stimulate and TH-2-type cytokines inhibit NO production. For these reasons, cell-mediated immunity may be expected to have influence on NO synthesis and on the mechanisms leading to iron accumulation in the reticuloendothelial system.

Acute-Phase Reaction↗

PubMed1997

Autoimmune hemolytic anemia and positive Coombs test associated with ulcerative colitis.

OBJECTIVES: To estimate the frequency of autoimmune hemolytic anemia and Coombs positivity without overt hemolysis in ulcerative colitis, to determine possible subsets of patients with ulcerative colitis susceptible to this complication, and to assess the efficacy of the applied therapeutic modalities. METHODS: Three hundred and two patients with ulcerative colitis treated at the University Hospital of Heraklion, Crete, over a 6-yr period were included. Within this group, a subgroup of 152 patients were studied prospectively for the presence of a positive direct Coombs test. RESULTS: Autoimmune hemolytic anemia was diagnosed in five of 302 patients with ulcerative colitis (1.7%). One more patient developed Coombs-positive hemolytic anemia, attributed to sulfasalazine. A positive Coombs test without evidence of hemolysis was found in three of 152 patients (2%). The mean age of all Coombs-positive patients was 50.5 yr, and there was a definitive male preponderance (male: female, 2:1). Autoimmune hemolytic anemia occurred during active colitis in all cases. The mean time between the onset of colitis and the diagnosis of autoimmune hemolytic anemia was 17 months. Three of five patients with autoimmune hemolytic anemia (60%) and seven of nine of all Coombs-positive patients (77.7%) had total colitis. All patients with autoimmune hemolytic anemia were treated initially with large doses of corticosteroids. Three of five (60%) had good hematological responses. One patient responded to the addition of azathioprine, and one underwent splenectomy and proctocolectomy. CONCLUSIONS: In this study, the frequency with which autoimmune hemolytic anemia was associated with ulcerative colitis was higher than in previous reports. The complication occurred early in the course of colitis and was related to activity and extent of the disease. In contrast to others studies, we found a preponderance of males. Although corticosteroids and/or immunosuppressive therapy was successful in most of our cases, one patient required surgery.

Adolescent↗

PubMed1998

Autoimmune premature ovarian failure: of mice and women.

Autoimmunity is a well-established mechanism of premature ovarian failure and may be the dominant cause of reversible premature ovarian failure. Because of its strong analogy with the human disease, murine experimental post-thymectomy autoimmune oophoritis may provide insight into the pathogenesis of autoimmune premature ovarian failure in women and might open new avenues to specific diagnostic and therapeutic methods. We reviewed the literature on murine experimental post-thymectomy autoimmune oophoritis in order to compare and contrast it with human autoimmune premature ovarian failure, to which it is similar in several ways. The histologic distribution of the ovarian lymphocytic infiltration is similar, and both have reduced natural killer cell activity. Susceptibility appears to be associated with genes outside the major histocompatibility complex in both the mouse and the human. Finally, the mouse model disorder is associated with a persistent neonatal-like Th2 response, which suggests possible similarities with autoimmune polyglandular failure type 1 in humans. In this condition autoimmunity develops despite an impaired cellular immune response.

Animals↗

PubMed1998

Induction of autoimmune arthritis in HLA-DR4 (DRB1*0401) transgenic mice by immunization with human and bovine type II collagen.

Although associations between the expression of particular HLA genes and the susceptibility to specific autoimmune diseases has been known for some time, the role that these HLA molecules play in the autoimmune response is unclear. Through the establishment of a chimeric HLA-DR/I-E transgene, we have examined the function of the rheumatoid arthritis (RA) susceptibility allele HLA-DR4 (DRB1*0401) in presenting antigenic peptides derived from the model Ag, type II collagen (CII), and in mediating an autoimmune response. As a transgene, the chimeric DR4 molecule conferred susceptibility to an autoimmune arthritis induced by immunization with human CII or bovine CII. These mice developed an inflammatory, autoimmune arthritis that was similar both histologically and in severity to that previously described for the collagen-induced arthritis model. The DR4-mediated autoimmune arthritis was accompanied by T cell and B cell responses to both the immunogen and the autoantigen, murine CII. The DR4-restricted T cell response to human CII was focused on an immunodominant determinant within CII263-270 and a minor determinant within CII286-300, the same CII determinants recently identified for yet another RA susceptibility allele, HLA-DR1 (DRB1*0101). Thus these data demonstrate that, like HLA-DR1, HLA-DR4 is capable of binding peptides derived from human CII and therefore probably plays a role in the autoimmune response to human CII observed in RA patients.

Amino Acid Sequence↗

PubMed1999

Antigen-specific T cells in autoimmune diseases with a focus on multiple sclerosis and experimental allergic encephalomyelitis.

Although the pathogenesis of autoimmune diseases remains poorly understood, the current view is that autoaggresive antigen-specific T cells play a central role in the cascade of events leading to most autoimmune diseases. A major event in the development of autoimmune diseases is the activation of antigen-specific T cells-how, when and where does this activation take place? This review addresses questions concerning the occurrence of unique autoantigens triggering autoimmune diseases, the factors influencing the balance between self-tolerance and autoaggresive immunity, and the mechanisms by which dendritic cells mediate immunity and tolerance to antigen-specific T cells. Knowledge of how antigen-specific T cells are activated is now being used to develop therapeutic approaches to control autoimmune diseases. We discuss tolerance to antigen-specific T cells and tolerance induction as treatment of T-cell-mediated autoimmune diseases. Therapeutic modalities have been established which selectively target the pathogenic T cells. leaving the remainder of the immune system intact.

Animals↗

PubMed2025

TYK2 :p.Pro1104Ala Variant Protects Against Autoimmunity by Modulating Immune Cell Levels.

The TYK2:p.Pro1104Ala (rs34536443) hypomorph variant has been associated with protection against numerous autoimmune disorders. Thus, its mechanism of action becomes of great interest. Here, consistent with the participation of activated immune cells in autoimmunity, we show that the variant regulates the levels of immune cells at a human, general population level and is associated particularly with higher levels of T and B lymphocytes, especially the naïve (non-activated) compartment. Also, consistent with a protective function in autoimmunity, the level of regulatory CD4+ T cells was increased. Thus, this variant decreases immune activation thereby protecting from autoimmunity. Our work links the cellular mechanism regulated by the TYK2:p.Pro1104Ala variant to autoimmunity protection and supports TYK2 as a therapeutic target in autoimmunity.

Humans↗

PubMed1996

[The role of substance P in the spinal dorsal horn in the pathogenesis of autoimmune diseases].

The aim of the present study is to explore the role of immunosuppression mediated by substance P (SP) in spinal dorsal horn (SDH) in the pathogenesis of the autoimmune diseases. The experimental allergic neuritis (EAN), experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA) animal models were established in the guinea pigs and Wistar rats, respectively. The effects of alteration of SP activity in SDH on immune responses and the pathogenesis of the autoimmune diseases were observed. The results showed that decreasing activity of SP in SDH by pretreatment of capsaicin or intrathecal SP antagonist could enhance cellular and humoral immune responses and aggravate the autoimmune diseases, while intrathecal SP agonist could suppress the immunity and alleviate clinical signs. The contents of SP in SDH was elevated dramatically at the peak of immune responses. These results suggest that SDH SP might participate in the pathogenesis of the autoimmune diseases. The increase of SP contents in SDH may inhibit the immune system via unknown pathway and ease clinical severity of the autoimmune disease, where SP might act as neurotransmitter in the immunoregulation of the negative feedback. To elevate SP content in SDH might be beneficial to the autoimmune diseases.

Animals↗

PubMed1998

Systemic autoimmune features and multiple sclerosis: a 5-year follow-up study.

OBJECTIVES: To evaluate in patients with multiple sclerosis (MS) the occurrence of clinical systemic signs and biological autoimmune abnormalities, including positive titers of antinuclear antibodies and antiphospholipid antibodies, suggestive of autoimmune diseases that may affect the central nervous system. Also, to compare the clinical and magnetic resonance imaging features and evolution of MS in patients with and without autoimmune abnormalities. DESIGN AND PATIENTS: Prospective study of 161 patients fulfilling the criteria of having probable or definite MS hospitalized in our institution between November 1990 and June 1992. RESULTS: Among the 161 patients, 84 (52.1%) had at least 1 clinical and/or biological general sign suggestive of an autoimmune disease; 64 were followed up for 4 to 5 years. The diagnosis of MS was confirmed in 50 patients and is still pending in 14 of them. No significant difference was found between patients with MS who were free of autoimmune features and those with autoimmune abnormalities (MS plus) concerning the age of disease onset, the presenting symptoms and signs, symptoms found on neurologic examination, and the course of the disease. For all patients with confirmed MS, general signs were found in 13.3%, positive titers of antinuclear antibodies in 26%, and positive titers of antiphospholipid antibodies in 6.2%. CONCLUSIONS: Patients with MS with autoimmune features, including those with titers of antinuclear antibodies of 1:100 or less and/or antiphospholipid antibodies, are not different than others with MS, and therefore should not be excluded from clinical trials.

Adolescent↗

PubMed1988

The Y chromosome from autoimmune BXSB/MpJ mice induces a lupus-like syndrome in (NZW x C57BL/6)F1 male mice, but not in C57BL/6 male mice.

The Y chromosome of the BXSB mouse has been shown to be responsible for the acceleration of lupus-like autoimmune syndrome in inbred BXSB mice and in their F1 hybrids with NZB or NZW mice. To further define the role of this as yet unidentified gene linked to the BXSB Y chromosome, designated Yaa (Y chromosome-linked autoimmune acceleration), the Y chromosome was transferred from the BXSB strain to nonautoimmune C57BL/6 (B6) mice. The effect of the Yaa gene on the autoantibody formation and the development of glomerulonephritis was investigated in B6 mice and in their F1 hybrids with NZW mice. The presence of the BXSB Y chromosome was not able to induce significant autoimmune responses in B6 mice. However, (NZW x B6)F1 males bearing the BXSB Y chromosome developed a severe lupus-like autoimmune syndrome, as documented by the production of anti-DNA antibodies and gp70-anti-gp70 immune complexes and the development of lethal lupus nephritis. Both sexes of (NZW x B6)F1 hybrids without the BXSB Y chromosome were essentially normal. Our results suggest that (a) the BXSB Y chromosome by itself is not sufficient to initiate autoimmune responses in nonautoimmune B6 mice, and (b) it is able to induce autoimmune responses in mice potentially capable of developing the disease, but whose autosomal abnormality by itself is not sufficient to develop autoimmune diseases.

Animals↗

PubMed2006

Clinical and diagnostic aspects of encephalopathy associated with autoimmune thyroid disease (or Hashimoto's encephalopathy).

Encephalopathy associated with autoimmune thyroid disease, currently known as Hashimoto's encephalopathy, but also defined as corticosteroid-responsive encephalopathy associated with autoimmune thyroiditis, is a relatively rare condition observed in a small percentage of patients presenting with autoimmune thyroid disease. It consists of a subacute, relapsing-remitting, steroid-responsive encephalopathy characterised by protean neurologic and neuropsychiatric symptoms, diffuse electroencephalographic abnormalities and increased titres of antithyroid antibodies in serum and/or in cerebrospinal fluid. Most of the cases presenting this neurologic complication are affected by Hashimoto's thyroiditis or, less frequently, by other autoimmune thyroid diseases, chiefly Graves' disease. The pathogenesis of this encephalopathy is still unknown and largely debated, because of extremely varied clinical presentation, possibly referable to different aetiologic and pathophysiologic mechanisms, as confirmed by the two clinical cases we report in this paper. Autoimmune aetiology is, however, very likely in view of the well established favourable response to corticosteroid administration. Both vasculitis and autoimmunity directed against common brain-thyroid antigens represent the most probable aetiologic pathways. Clinical manifestations include consciousness changes, neurologic diffuse or focal signs, headache, and altered cognitive function. Although unspecific, cerebral oedema has also been described. Cerebrospinal fluid examination often discloses an inflammatory process, with a mild increase in protein content and occasionally in lymphocyte count. In this review, clinical criteria for the diagnosis of defined, probable, or possible encephalopathy associated with autoimmune thyroid disease are suggested. Corticosteroid therapy currently allows us to obtain rapid remission of disease symptoms, but adverse outcomes as well as spontaneous remissions have also been reported.

Adrenal Cortex Hormones↗

PubMed1999

Cellular and molecular roles of beta cell autoantigens, macrophages and T cells in the pathogenesis of autoimmune diabetes.

Type I diabetes, also known as insulin-dependent diabetes mellitus (IDDM) results from the destruction of insulin-producing pancreatic beta cells by a progressive beta cell-specific autoimmune process. The pathogenesis of autoimmune IDDM has been extensively studied for the past two decades using animal models such as the non-obese diabetic (NOD) mouse and the BioBreeding (BB) rat. However, the initial events that trigger the immune responses leading to the selective destruction of the beta cells are poorly understood. It is thought that beta cell autoantigens are involved in the triggering of beta cell-specific autoimmunity. Among a dozen putative beta cell autoantigens, glutamic acid decarboxylase (GAD) has been proposed as perhaps the strongest candidate in both humans and the NOD mouse. In the NOD mouse, GAD, as compared with other beta cell autoantigens, provokes the earliest T cell proliferative response. The suppression of GAD expression in the beta cells results in the prevention of autoimmune diabetes in NOD mice. In addition, the major populations of cells infiltrating the islets during the early stage of insulitis in BB rats and NOD mice are macrophages and dendritic cells. The inactivation of macrophages in NOD mice results in the prevention of T cell mediated autoimmune diabetes. Macrophages are primary contributors to the creation of the immune environment conducive to the development and activation of beta cell-specific Th1-type CD4+ T cells and CD8+ cytotoxic T cells that cause autoimmune diabetes in NOD mice. CD4+ and CD8+ T cells are both believed to be important for the destruction of beta cells. These cells, as final effectors, can kill the insulin-producing beta cells by the induction of apoptosis. In addition, CD8+ cytotoxic T cells release granzyme and cytolysin (perforin), which are also toxic to beta cells. In this way, macrophages, CD4+ T cells and CD8+ T cells act synergistically to kill the beta cells in conjunction with beta cell autoantigens and MHC class I and class II antigens, resulting in the onset of autoimmune type I diabetes.

Animals↗

PubMed1999

Prevention of autoimmune but not allogeneic destruction of grafted islets by different therapeutic strategies.

Grafting autoimmune-diabetic recipients with allogeneic islets, graft rejection and disease recurrence as major problems of reaching indefinite survival and tolerance induction have to be solved. Anti-CD25 and anti-CD4 monoclonal antibodies were successfully used after allogeneic islet transplantation in experimentally diabetic rats. A temporary anti-CD25 therapy also prevented disease recurrence in autoimmune-diabetic BB rats, while this was not yet reported for an anti-CD4 treatment. In autoimmune-diabetic NOD mice disease recurrence can be successfully treated using an anti-CD4 monoclonal antibody. We, therefore, compared the efficacy of a short-term anti-CD25 and anti-CD4 treatment regarding the prevention of allograft rejection and disease recurrence in autoimmune-diabetic BB/OK rats. Both monoclonal antibodies were combined with low doses of Cyclosporin A. Untreated BB/OK rats relapsed into hyperglycaemia within 3 weeks independent of the islet donor, LEW.1A, LEW.1BB/OK or BB/OK rats. However, after grafting MHC-identical allogeneic (LEW.1BB/OK) or syngeneic (BB/OK) islets we observed about 30% spontaneous acceptance. Both the anti-CD25 and anti-CD4 therapy significantly prolonged the survival of allogeneic grafted islets. After MHC-identical allogeneic and syngeneic islet transplantation the temporary immunotherapy increased the proportion of permanent acceptors to 63% and 75%, respectively. The efficacy of both treatment strategies in prolonging allograft survival and prevention of disease recurrence was identical. In summary, anti-CD25 as well as anti-CD4 therapy prevented autoimmune but not allogeneic islet destruction in autoimmune-diabetic BB/OK rats. In conclusion, targeting different immune cells by monoclonal antibodies with different specificities can lead to very similar results with respect to an interruption of allograft rejection and autoimmune reaction.

Animals↗

PubMed1995

Immunosuppressive treatment prevents behavioral deficit in autoimmune MRL-lpr mice.

MRL-lpr mice, which develop severe autoimmune disease, explore novel objects less well than do their congenic MRL(-)+/+ controls, in which symptoms of the disease are relatively mild. Moreover, diminished exploration in MRL-lpr mice correlates with the elevated titers of antinuclear antibodies (ANA) in their sera, suggesting that this behavioral deficit is caused by the autoimmune process. To test the hypothesis that autoimmunity affects behavior, in this study we examine whether treatment of the autoimmune process will reduce the difference in performance between the two MRL substrains in the novel-object test. Forty mice in each substrain were treated from 4 to 10 wk of age with the immunosuppressive drug, cyclophosphamide (100 mg/kg/wk, IP) or a saline vehicle. The immunosuppressive treatment reduced ANA titers to low levels and eliminated ANA production completely in 55% of MRL-lpr mice, suggesting an attenuation of the autoimmune process. In addition, treatment with cyclophosphamide, but not saline, abolished significant differences in exploration between the MRL-lpr and MRL +/+ groups, as measured by the latency to touch a novel object and the time spent exploring it. Thus, the present results suggest that a treatment which ameliorates autoimmune symptoms can concurrently remove the substrain difference in behavior. The effect of cyclophosphamide in the MRL-lpr group is believed to reflect the suppression of pathogenic immune factor(s) that alter behavior during the onset of autoimmune disease.

Animals↗

PubMed2006

Inflammation: a pivotal link between autoimmune diseases and atherosclerosis.

Premature coronary heart disease has emerged as a major cause of morbidity and mortality in systemic autoimmune diseases. Recent epidemiologic and pathogenesis studies have suggested a great deal in common between the pathogenesis of prototypic autoimmune disease such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and that of atherosclerosis. Some of the most remarkable data in support of a link between autoimmunity and atherosclerosis comes from epidemiological studies of patients with autoimmune disorders (RA and SLE). Many epidemiologic observations have linked systemic inflammation with the cardiovascular events in autoimmune disease such as RA and SLE. Inflammation is increasingly being considered central to the pathogenesis of atherosclerosis and an important risk factor for vascular disease. Systemic inflammation may be regarded as accelerating the atherosclerotic process. Systemic levels of soluble inflammatory mediators such as C-reactive protein (CRP) have been associated with cardiovascular risk in the general population. CRP, or more specifically high sensitivity-hsCRP, is a marker of systemic inflammation that has been identified as a valid biomarker of cardiovascular risk. Furthermore, the immunomodulatory and anti-inflammatory actions of statins may affect their utility in the context of chronic inflammatory autoimmune disease. Thus, effective control or dampening of inflammation, with such agents, should be included in the therapeutic armamentarium of autoimmune diseases with the aim of protecting against cardiovascular disease.

Animals↗

PubMed2005

How viral infections affect the autoimmune process leading to type 1 diabetes.

Despite a large body of evidence describing associations between viruses and the development of type 1 diabetes (T1D) in genetically prone individuals, clearly defining causative infectious agents has not been successful. A likely explanation is that the link between infections and autoimmunity is more multifaceted than we initially assumed. Viral footprints might be hard to detect systemically or in the target organ once autoimmunity has been initiated, and several infections might have to act in concert to precipitate clinical autoimmunity. Furthermore, cells cross-reactive between viral and self-antigens might express low avidity T cell receptors and only be present transiently in the blood of affected individuals. In addition, there are two new observations from animal models that we should take into account at this point: first, viral infections alone might not be able to induce disease in the absence of other inflammatory factors (supporting the "fertile field hypothesis" [M.G. von Herrath et al., Microorganisms and autoimmunity: making the barren field fertile? Nat. Rev. Microbiol. 1 (2003) 151-157, ]). Second, increasing evidence indicates that viruses can play a role in preventing rather than enhancing T1D development (supporting the "hygiene hypothesis" [J.F. Bach, Protective role of infections and vaccinations on autoimmune diseases. J. Autoimmun. 16 (2001) 347-353]). In this article we will present an overview of the early events and requirements that could account for T1D predisposition and development, and explain how these can be modulated by viral infections. Focusing on coxsackie B and lymphocytic choriomeningitis virus infections, we will discuss new data that can hopefully help us understand how virus-induced inflammation can positively or negatively affect the clinical outcome of islet-autoimmunity and T1D.

Animals↗

PubMed2006

Oxidative and nitrosative stress in trichloroethene-mediated autoimmune response.

Reactive oxygen and nitrogen species (RONS) are implicated in the pathogenesis of several autoimmune diseases. Also, increased lipid peroxidation and protein nitration are reported in systemic autoimmune diseases. Lipid peroxidation-derived aldehydes (LPDAs) such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are highly reactive and bind proteins covalently, but their potential to elicit an autoimmune response and contribution to disease pathogenesis remain unclear. Similarly, nitration of protein could also contribute to disease pathogenesis. To assess the status of lipid peroxidation and/or RONS, autoimmune-prone female MRL+/+ mice (5-week old) were treated with trichloroethene (TCE), an environmental contaminant known to induce autoimmune response, for 48 weeks (0.5mg/ml via drinking water), and formation of antibodies to LPDA-protein adducts was followed in the sera of control and TCE-treated mice. TCE treatment led to greater formation of both anti-MDA- and -HNE-protein adduct antibodies and higher serum iNOS and nitrotyrosine levels. The increase in TCE-induced oxidative stress was associated with increases in anti-nuclear-, anti-ssDNA- and anti-dsDNA-antibodies. These findings suggest that TCE exposure not only leads to oxidative/nitrosative stress, but is also associated with induction/exacerbation of autoimmune response in MRL+/+ mice. Further interventional studies are needed to establish a causal role of RONS in TCE-mediated autoimmunity.

Aldehydes↗

PubMed1992

Detection of brain-reactive autoantibodies in the sera of autoimmune mice using ELISA.

There are considerable problems with developing an assay to detect the often small quantities of autoantibodies which react against antigens in a heterogeneous and complex mixture from a source such as brain. An indirect enzyme-linked immunosorbent assay (ELISA) has been developed which can detect naturally occurring autoantibodies in serum that are reactive with integral brain membrane antigens. Sera were collected from autoimmune BXSB and NZB mice and non-autoimmune C57BL/6 mice at various ages and were assayed for the presence of brain-reactive autoantibodies (BRAAs). It is shown that this technique provides a highly sensitive, specific, and rapid assay for detecting BRAAs in serum. It shows that integral membrane antigens from whole brain can be isolated and used to detect and quantitate antibodies in the sera of autoimmune and non-autoimmune mice. The data also confirm studies, using different techniques, showing higher levels of autoantibodies to brain in autoimmune as compared to non-autoimmune mice. There are numerous potential applications for this ELISA, such as in rapidly screening large numbers of samples of biological fluids, tracking autoimmune disease progression over time, detecting small quantities of antibody against brain antigens, and as an assay system for investigating the role of BRAAs in the pathogenesis of immune mediated CNS disease.

Animals↗