Journal of autoimmune diseases最新文献

The Cytochrome-P-450 enzymes (CYP) are among the most important xenobiotic-metabolizing enzymes, which produce reactive oxygen species (ROS) as the result of metabolizing xenobiotics. ROS are believed to play important roles in the pathophysiology of autoimmune diseases. ROS can alter the structure of cellular antigens to produce a "neo-antigen" which could mount an autoimmune response against the original antigen through molecular mimicry. ROS are involved in apoptosis, activation of antigen presenting cells and initiation or amplification of diverse immunologic reactions. Taking all these facts together, it could be speculated that CYP may be involved in the initiation and/or amplification of autoimmune phenomena.

The antiphospholipid syndrome is an autoimmune disease characterised by recurrent arterial or venous thrombosis, pregnancy morbidity and the persistence of positive antiphospholipid antibodies. Many other clinical manifestations may occur including heart valve disease, livedo reticularis, thrombocytopenia and neurological manifestations such as migraine and seizures. We review a number of other manifestations including stenotic lesions, coronary artery disease and accelerated atherosclerosis, skeletal disorders and the concept of seronegative antiphospholipid syndrome.

Background: Antibodies against Ro-52 have been described in patients with a broad spectrum of autoimmune disease, most commonly in association with anti-Ro-60 in systemic lupus erythematosus and Sjogrens syndrome. However, in inflammatory myositis anti-Ro-52 is frequently present without anti-Ro-60 and is closely linked to the presence of aminoacyl-tRNA synthetase (aats) antibodies. To date there have been no comprehensive reports on the frequency of anti-Ro-52 in systemic sclerosis (SSc), a disease characterised by hallmark autoantibodies that occur in non-overlapping subsets. Clinically, each antibody-defined group has a distinct pattern of organ involvement, some featuring myositis.

Objectives: To determine the frequency of anti-Ro-52 in serologically defined groups of SSc patients and to investigate a possible link with myositis-associated autoantibodies.

Methods: Serum samples from 1010 patients with SSc and 55 and 32 patients with anti-aats and anti-Ku respectively were tested for the presence of anti-Ro-52 using a commercial ELISA.

Results: The prevalence of anti-Ro-52 was 15-38% in nine of the eleven sub-groups. There were no significant differences in mean anti-Ro-52 levels in these groups with the exception of that defined by the presence of anti-U1-RNP. In the remaining groups defined by anti-Ro-60 and anti-aats, anti-Ro-52 was present in 92% and 100% respectively. In sera from non-SSc patients with anti-aats, anti-Ro-52 was detected in 64%.

Conclusion: Anti-Ro-52 is present throughout the SSc population. It is neither more prevalent in the myositis-associated antibody groups nor does it segregate with any other major SSc-specific autoantibodies. The co-existence of anti-Ro-52 with both anti-Ro-60 and anti-aats is confirmed.

Introduction: Idiopathic systemic vasculitis represents a group of clinical entities having non-specific etiology with the common characteristic of acute or chronic inflammatory compromise of the small and large vessels walls, associated with fibrinoid necrosis.

Objectives: To describe the most common inflammatory vascular diseases in a long historical cohort of patients from San Juan de Dios Hospital located in Bogota, Colombia using two different systems and a clinical histopathological correlation format, and to make a comparison between them.

Methods: We reviewed all previously ascertained cases of vasculitis confirmed by biopsy processed between 1953 and 1990, and systematically collected data on all new cases of vasculitis from 1991 to 1997 at the Hospital San Juan de Dios (Bogota-Colombia). The cases were classified in accordance with the Chapel Hill Consensus criteria, and the system proposed by J.T. Lie.

Results: Of 165,556 biopsy tissue specimens obtained during this period from our hospital, 0.18% had vasculitis, perivasculitis or vasculopathy. These included 304 histopathological biopsies from 292 patients. Cutaneous leukocytoclastic vasculitis (64 histological specimens) was the most frequently encountered type of "primary" vasculitis followed by thromboangiitis obliterans (38 specimens), and polyarteritis nodosa (24 specimens). Vasculitis associated with connective tissue diseases (33 specimens) and infection (20 specimens) were the main forms of secondary vasculitis, a category that was omitted from the Chapel Hill consensus report. We found that 65.8% of our histopathological diagnoses could not be classified according to the Chapel Hill classification, and 35.2% could not be classified according to the classification of Lie. Only 8.9% of cases remained unclassified by our system after clinical and histological correlation.

Conclusion: Current vasculitis classification schemes are designed for classification, rather that diagnosis of disease and do not adequately address some common forms of inflammatory vascular diseases, including those of infectious etiology and unusual etiology seen in clinical practice. Based on our clinical experience, we suggest a classification outline which practitioners can use which emphasizes correlation of the clinical picture to the histopathology findings for diagnosis and therapy, which may promote better clinical practice and standardization for clinical trials.

Patients with antiphospholipid syndrome are at increased risk for recurrent arterial and venous thrombosis and therefore benefit from long term warfarin therapy. The optimal duration of warfarin therapy after a first venous thromboembolic event is however a matter of some controversy and many questions remain unanswered. After reviewing and analysing the available evidence, we discuss some common scenarios in everyday clinical practice where treatment decisions are difficult.

Background: Systemic vasculitides constitute a heterogeneous group of diseases of autoimmunological origin characterized by inflammation of blood vessels and antibodies that react against autoantigens in a process that ultimately affects blood vessel walls. An important number of these patients present kidney disease. An endeavour of this area of research is the identification of autoantigens involved in these diseases. Accordingly, we used serum from a patient suffering from a microscopic polyangiitis, P-ANCA positive, manifesting a clinically atypical renal necrotizing glomerulonephritis and interstitial nephropathy for the identification of autoantigens; we also determined the prevalence of corresponding autoantibodies in other vasculitides, diabetic microangiopathy and in general population.

Methods: The patient's serum was used as a probe for the immunoscreening method SEREX to screen a human brain cDNA expression library.

Results: Four positive clones were isolated and sequenced. Clones Jos002 code for protein HDAC5, Jos014 for TFC4, Jos107 for RTF1, and Jos313 for POLDIP3 polymerase. The four proteins are of nuclear localization. None of them had been reported as autoantigen. Recombinant proteins were synthesised and checked as antigens by western blot with different sera from controls and patients affected with other vasculitides and diabetic microangiopathy as well. Only the serum from the patient origin of this study recognized all recombinant proteins.

Conclusion: We identify four nuclear proteins, HDAC5, TFC4, RTF1 and POLDIP3 polymerase as new autoantigens that could be used as markers in the diagnosis of subfamilies in immune diseases, although we cannot determine the role of these proteins in the aetiopathogenic process.

Background: Multiple sclerosis (MS) risk, over 10-fold higher in Western than in Asian countries, is associated with elevated IgG antibody titers against Epstein-Barr viral capcid antigen (anti-EBVCA IgG titers). Given the 84% homology of the open reading frame BCRF1 of Epstein-Barr virus (EBV) to human interleukin 10 (hIL-10) and the remarkable Caucasian-vs.-Asian population differences in hIL-10 gene promoter polymorphisms, this strong association of MS risk with anti-EB-VCA IgG titers may be explained by the genetic variations in the hIL-10 gene.

Methods: We evaluated anti-EB-VCA IgG titers in association with a single nucleotide polymorphism (SNP) in the promoter of hIL-10 at position -819 (hIL-10 T-819C) in a cross-sectional survey of 241 Japanese. Anti-EB-VCA IgG titer and its elevation (> or = 1:160) were evaluated, stratified by sex and hIL-10 T-819C genotype.

Results: The cytosine-allele frequencies at hIL-10 T-819C were 32.9% in women and 30.9% in men. These are consistent with the published reports of Japanese and Chinese, but substantially lower than those of Caucasians (> 70%). In women, the proportion with elevated anti-EB-VCA IgG titers (> or = 1:160) increased appreciably from 53.7% in the T/T genotype group to 66.7% in the T/C group and to 83.3% in the C/C group (P-trend = 0.037). The titers did not differ by the hIL-10 T-819C genotype in men.

Conclusion: Anti-EB-VCA IgG titers may increase with the number of cytosine alleles at hIL-10 T-819C in women. This observed gender specific association in Japanese warrants further investigation, especially in Western populations with high MS risk.

Background: Organ-specific autoimmune diseases affect particular targets in the body, whereas systemic diseases engage multiple organs. Both types of autoimmune diseases may coexist in the same patient, either sequentially or concurrently, sustained by the presence of autoantibodies directed against the corresponding autoantigens. Multiple factors, including those of immunological, genetic, endocrine and environmental origin, contribute to the above condition. Due to association of certain autoimmune disorders with HLA alleles, it has been intriguing to examine the immunogenetic basis for autoantigen presentation leading to the production of two or more autoantibodies, each distinctive of an organ-specific or systemic disease. This communication offers the explanation for shared autoimmunity as illustrated by organ-specific blistering diseases and the connective tissue disorders of systemic nature.

Presentation of the hypothesis: Several hypothetical mechanisms implicating HLA determinants, autoantigenic peptides, T cells, and B cells have been proposed to elucidate the process by which two autoimmune diseases are induced in the same individual. One of these scenarios, based on the assumption that the patient carries two disease-susceptible HLA genes, arises when a single T cell epitope of each autoantigen recognizes its HLA protein, leading to the generation of two types of autoreactive B cells, which produce autoantibodies. Another mechanism functioning whilst an epitope derived from either autoantigen binds each of the HLA determinants, resulting in the induction of both diseases by cross-presentation. Finally, two discrete epitopes originating from the same autoantigen may interact with each of the HLA specificities, eliciting the production of both types of autoantibodies.

Testing the hypothesis: Despite the lack of immediate or unequivocal experimental evidence supporting the present hypothesis, several approaches may secure a better understanding of shared autoimmunity. Among these are animal models expressing the transgenes of human disease-associated HLA determinants and T or B cell receptors, as well as in vitro binding studies employing purified HLA proteins, synthetic peptides, and cellular assays with antigen-presenting cells and patient's lymphocytes. Indisputably, a bioinformatics-based search for peptide motifs and the modeling of the conformation of bound autoantigenic peptides associated with their respective HLA alleles will reveal some of these important processes.

Implications of the hypothesis: The elucidation of HLA-restricted immune recognition mechanisms prompting the production of two or more disease-specific autoantibodies holds significant clinical ramifications and implications for the development of more effective treatment protocols.