Celiac disease and autoimmunity.
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Autoantibodies↗
Biomedical subjects
M Blank
Publications and source records attributed to M Blank.
Anti-topoisomerase-I and clinical findings in systemic sclerosis (scleroderma).
The relationship between anti-topoisomerase-I antibodies and clinical findings was studied in 191 patients with definite systemic sclerosis. This was done by performing ELISA to detect antibodies to recombinant topoisomerase-I. Antibodies to topoisomerase-I were found in 72 patients (37%) with systemic sclerosis, which is a higher percentage than reported in most previous reports on a large unselected population. In 43 patients the presence of antibodies to recombinant topoisomerase-I was confirmed using both the immunodiffusion method and ELISA, with similar results. When classified into diffuse versus limited disease, a significant difference in antibody prevalence was demonstrated (P < 0.005), thus indicating that anti-topoisomerase-I antibody detection with ELISA may assist in early identification of systemic sclerosis subtypes.
Autoantibodies↗
[Th1/Th2 cells and autoimmunity].
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Autoimmunity↗
Immunointerventions in experimental model for antiphospholipid syndrome.
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Animals↗
Ethnic segregation of HTLV-I and HTLV-II carriers among South American native Indians.
To investigate the genetic background of human T-cell leukemia virus type I (HTLV-I) and II (HTLV-II) carriers among South American native Indians, we analyzed HLA DRB1*-DQB1* haplotypes of the virus carriers from Andes highlands and Orinoco lowlands by the PCR-RFLP genotyping method. It was revealed that the HTLV-I-carrying Andes natives had one of the 5 HLA haplotypes: DRB1*-DQB1* 0403-0302, 0802-0402, 0901-0303, 1406-0302 and 0407-0302, and that the Orinoco HTLV-II carriers had one of the 3 HLA haplotypes: DRB1*-DQB1* 1402-0301, 1602-0301 and 0404-0302. The HLA haplotypes of Andes HTLV-I carriers and Orinoco HTLV-II carriers were mutually exclusive. The haplotypes associated with HTLV-I carriers were commonly found among the Andes Indians and Japanese, which is the known HTLV-I endemic population, while the haplotypes associated with HTLV-II carriers were specifically found among the Orinoco Indians and North American Indians, among whom HTLV-II is endemic. These results suggested that HLA haplotypes might be ethnically segregated among South American natives and might be involved in the susceptibility to HTLV-I and HTLV-II infections.
Alleles↗
HTLV-II detection in an Amerindian family in Colombian southern Andean region.
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Adult↗
Infective dermatitis in Colombia.
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Child, Preschool↗
Hepatitis C seroprevalence amongst injecting drug users attending a methadone programme.
AIM: To study the seroprevalence of the hepatitis C virus (HCV) amongst a population of injecting drug users and to examine the relationship between potential risk factors and HCV infection. METHODS: A sample of 116 clients attending a methadone treatment clinic in Christchurch took part in this study. Blood samples were analysed to detect antibodies to HCV and to test for HCV RNA: Serum transaminases were also measured. In addition a short questionnaire about sexual behaviour and drug use practices was self completed by all participants in strictest confidence. RESULTS: Slightly more than half the sample were female (54.3%) and most were of European origin (90.6%). The average age was 31.56 years and the average length of time they had been injecting drugs was 9.54 years. HCV antibodies were detected in 84.2% of the sample and HCV RNA in 66.1% of the sample including 75.9% amongst those who were anti-HCV positive and 16.6% amongst those who were anti-HCV negative. AST and ALT levels were elevated amongst 16.8% and 46.2% of the sample respectively. The likelihood of being anti-HCV positive increased with years of drug use and with increased sharing of injecting equipment. No significant relationship between HCV status and sexual practices was evident. Data on the history of drug using practices indicated that sharing of injecting equipment had become less common over time and access to new equipment through reliable sources had become more common with time. CONCLUSIONS: HCV is widespread amongst this population of injecting drug users suggesting the possibility of a major clinical and social problem. Despite evidence of a reduction in the sharing of injecting equipment, HCV transmission is still occurring indicating the potential for other parenterally transmitted diseases, such as HIV, to become established amongst injecting drug users. Those at high risk of HCV should be discouraged from donating blood because of the possibility of HCV seronegative infectivity.
Adult↗
Bromocriptine immunomodulation of experimental SLE and primary antiphospholipid syndrome via induction of nonspecific T suppressor cells.
Bromocriptine (BRC) is a dopamine agonist that suppresses the secretion of prolactin by the pituitary gland and is known to have immunomodulating properties. In the present study, we investigated the effect of BRC on the development of two autoimmune experimental models: (i) systemic lupus erythematosus (SLE), induced by injection of a human anti-dsDNA monoclonal antibody (MIV-7); (ii) primary anti-phospholipid syndrome (PAPS), induced by injection of a mouse anticardiolipin monoclonal antibody (CAM). BRC had a suppressive effect on in vivo autoantibody production, as well as on the appearance of other manifestations of the respective disease. The BRC activity seems to be nonspecific, since the same effect was demonstrated in mice with lupus and with PAPS. These data were supported by the in vitro nonspecific effect of CD8 cells induced in vivo by bromocriptine, on specific lymph node cell proliferation in the presence of the pathogenic monoclonal antibodies (MIV-7 or CAM, respectively), and on the response to an irrelevant autoantigen, myelin basic protein. These data were complemented by the nonspecific suppressive effect by the T-suppressor factor, produced by the CD8 cells, on specific thymidine uptake by lymph node cells from experimental SLE or PAPS in the presence of the immunizing mAb. Injection of CD8 cells from BRC-treated mice with SLE or PAPS abolished the disease development in the lupus and PAPS experimental models. The data suggest a possible novel role of bromocriptine in downregulating autoimmune phenomena through induction of natural nonspecific CD8+ suppressor cells.
Animals↗
Transfer of experimental antiphospholipid syndrome by bone marrow cell transplantation. The importance of the T cell.
OBJECTIVE: To investigate the potential of bone marrow cells from mice with primary antiphospholipid syndrome (APS) to transfer the disease to naive mice, and to determine the importance of the role of T cells in the APS. METHODS: Experimental primary APS was induced in naive mice following active immunization with anticardiolipin (aCL) monoclonal antibody (MAb). Whole-population or T cell-depleted bone marrow cells from mice with experimental primary APS were infused into total body-irradiated naive BALB/c recipients. RESULTS: Bone marrow cells (in the presence of T cells) had the potential to induce experimental APS in naive mice, which resulted in high serum titers of aCL, antiphosphatidylserine, and antiphosphatidylinositol antibodies; an increased number of antibody-forming cells specific for each of the above phospholipids; a positive lymph node cell proliferative response to aCL MAb; and clinical features of primary APS, including thrombocytopenia, prolonged activated partial thromboplastin time (indicating the presence of lupus anticoagulant), and a high frequency of fetal resorptions (the equivalent of human fetal loss). T cell-depleted bone marrow cells did not transfer the disease. CONCLUSION: This study demonstrates the important role of T cells in the development and transfer of experimental primary APS and raises the possibility of T cell manipulations in treatments to prevent this condition.
Animals↗
Characterization of biologically active antineutrophil cytoplasmic antibodies induced in mice. Pathogenetic role in experimental vasculitis.
OBJECTIVE: To investigate the pathogenetic role of antineutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis (WG). METHODS: BALB/c mice were immunized with human IgG ANCA from a patient with WG. Control mice were immunized with normal human IgG. Levels of mouse ANCA and other autoantibodies were determined. Mouse ANCA were tested for their ability to induce adhesion and respiratory burst of neutrophils. The mouse lungs and kidneys were examined for the development of vasculitis. RESULTS: Mice immunized with human ANCA developed anti-human ANCA and anti-anti-human ANCA (mouse ANCA), while the controls did not develop these antibodies. Mouse ANCA were capable of inducing adhesion of neutrophils to fibronectin and activating the respiratory burst in neutrophils. Moreover, the mice that were immunized with human ANCA developed perivascular mononuclear cell infiltrates in the lungs, suggesting vasculitis. CONCLUSION: The results suggest a pathogenic role of ANCA in WG, and may imply that activation of neutrophils is the initiating event in the development of vasculitis in WG.
Animals↗
Absence of anti-idiotypic antibodies in IVIG preparations to autoantibodies of rare autoimmune diseases.
Intravenous immunoglobulins (IVIG) were found to contain anti-idiotypic antibodies against autoantibodies of various autoimmune diseases. We examined commercial IVIG preparations, from three different manufactures, for the presence of autoantibodies and anti-idiotypic antibodies of two rare autoimmune diseases--primary biliary cirrhosis [anti-pyruvate dehydrogenase (PDH) antibodies] and Goodpasture's syndrome (anti-NC1 antibodies). We used ELISA studies as well as immunoblotting and anti-PDH enzyme activity for the detection of anti-PDH antibodies. ELISA and immunofluorescence studies were used for the detection of anti-NC1 antibodies. The presence of anti-idiotypic activity against anti-PDH fragments on Sepharose-bound IVIG [F(ab)2]. Anti-anti-NC1 activity was evaluated employing inhibition ELISA and immunofluorescence studies. The commercial IVIG preparations that were examined did not contain anti-PDH or anti-NC1 antibodies nor anti-idiotypic activity against these autoantibodies. We conclude that commercial IVIG may lack anti-idiotypic activity against rare autoantibodies.
Anti-Glomerular Basement Membrane Disease↗
Multiple autoantibodies in patients with silicone breast implants.
Diverse immunologic abnormalities have been described in women who received silicone breast implants. However, most studies have focused on either a limited number of patients or a small panel of autoantibodies. We report the analysis of 20 autoantibodies in 116 women with implants and 134 controls. The patients ranged from 26- to 66-years-old, with a mean of 45.7 +/- 8.3 years; breast prostheses were in place for a mean of 15 +/- 5.6 years, with a range of 4 to 30, the chief complaints of the 116 patients included polyarthralgias, fatigue, myalgias, morning stiffness, and decreased memory. All 250 sera were tested blindly using a panel of 20 autoantigens including SS-A, SS-B, RNP, cardiolipin (CL), collagen types I, II and IV, phosphatidylserine (PS), myeloperoxidase (MPO), sulfatides (sulf), thyroglobulin (TG), gangliosides (GDIa;GM2), proteinase-3 (PR3), Jo-1, Sm, HPRPP-ribosomal phosphate, histones (H2AH2B), Scl-70 and glomerular basement membrane (NC-1). Values from individual patients were considered positive only when greater than 3 SD above the control mean. There was a statistically significant greater frequency of autoantibodies in women with implants for 15 of the 20 autoantigens; these were particularly striking for anti-H2AH2B, HPRPP, SS-A, SS-B, Scl-70, CL, PS, GM2, and NC-1. Many patients harbored several autoantibodies; 20% had four autoantibodies; 8% had six autoantibodies. The association of autoantibodies and implants suggests an adjuvant action of silicon/silicone byproducts.
Adjuvants, Immunologic↗
Natural autoantibodies in sera of patients with Gaucher's disease.
Gaucher's disease (GD) is associated with hyperactivity of the immune system, which manifests by polyclonal hypergamma-globulinemia and an increased incidence of monoclonal gammopathies in GD patients. We analyzed sera of 43 patients with GD for the presence of autoantibodies against 14 autoantigens. The results demonstrated a significant increase in the incidence of all autoantibodies tested, ranging from 11% for anti-RNP, pyruvate dehydrogenase (PDH), and DNA antibodies to 57% for rheumatoid factor. The autoantibodies were of all three isotypes, namely, IgG, IgM, and IgA. There was no correlation between the levels of immunoglobulins in the serum and the titer of autoantibodies found. Immunization of naive mice with a pool of purified anti-DNA antibodies form GD patients did not result in induction of experimental systemic lupus erythematosus (SLE), suggesting that they may represent natural autoantibodies that are not pathogenic. In conclusion, we found high titers of natural, polyspecific, nonpathogenic autoantibodies in the sera of GD patients.
Adolescent↗
Biological effects of environmental electromagnetic fields: molecular mechanisms.
In recent years, epidemiological studies have shown an increased risk of leukemia in children living near electric power distribution lines. Also, medical studies have shown that low frequency electromagnetic (EM) fields accelerate the healing of bone fractures. The stimulation of biosynthesis suggested by both epidemiological and clinical studies is observed in vitro, and indicates that EM fields stimulate the biosynthetic 'stress response' in cells. Studies of EM field effects on enzyme (Na,K-ATPase) function suggest that these effects should be considered in the design of molecular electronic devices.
Child↗
The pathogenic human monoclonal anti-DNA that induces experimental systemic lupus erythematosus in mice is encoded by a VH4 gene segment.
Systemic lupus erythematosus (SLE) can be induced in mice by immunization with a human anti-DNA IgM mAb that was derived from a patient with cold agglutinin disease. The latter anti-DNA mAb expresses the common idiotype (Id) designated 16/6 Id. The original human hybridoma 16/6 that secreted an IgM antibody that bound ssDNA and carried the 16/6 Id had switched in culture to secrete an IgG molecule. Herein we show that the IgG 16/6 antibody contains the previously reported characteristics of the original IgM 16/6 mAb: it expresses the 16/6 Id and is capable of inducing experimental SLE in susceptible mouse strains. The identify of the IgG 16/6 anti-DNA mAb to the original IgM mAb was shown both by serological techniques and at the T cell level. The human IgG 16/6 mAb was found to be encoded by a germline gene from the human VH4 gene family, with high similarity to the germline gene VH4.21 that was previously shown to code for anti-DNA antibodies isolated from SLE patients. The VH4.21 germline gene was found to also code for most antibodies with cold agglutinin activity that were isolated from patients with cold agglutinin disease.
Amino Acid Sequence↗
Immunization with anti-neutrophil cytoplasmic antibody (ANCA) induces the production of mouse ANCA and perivascular lymphocyte infiltration.
Wegener's granulomatosis (WG) is a granulomatous necrotizing vasculitis associated with the presence of ANCA, predominantly directed against proteinase 3 (PR3). The titres of ANCA correlate with disease activity and titre increases may precede disease exacerbations. Previously, we have shown that it is possible to induce autoimmune disease (systemic lupus erythematosus (SLE) and anti-phospholipid syndrome) in naive mice following active immunization with human autoantibodies, namely anti-DNA and anti-cardiolipin, respectively. The mice developed first anti-autoantibodies and, after about 4 months anti-anti-autoantibodies (Ab3), simulating auto-antibodies (Ab1) in their binding activities, and their presence was associated with the development of disease manifestations, characteristic of the human disease. So far, there is no good animal model for WG. In the current study we have immunized mice with human ANCA with the aim of inducing experimental WG. In two separate studies 30 mice were immunized in their footpads with autoantigen-purified IgG fraction (ANCA) from the sera of two patients with untreated WG, emulsified in Freund's complete adjuvant, followed 3 weeks later by ANCA injection in PBS. In the first experiment mice immunized with ANCA developed sterile microabscesses in the lungs after 8 months, and died after 8-15 months. In the second experiment, mice immunized with ANCA developed after 4 months mouse ANCA, with specificity both to PR3 and to myeloperoxidase, as well as anti-endothelial autoantibodies (AECA), as shown by radioimmunoprecipitation. Pathologically, the immunized mice developed proteinuria but not haematuria, and histological sections of the lungs demonstrated mononuclear perivascular infiltration, while diffuse granular deposition of immunoglobulins was noted in the kidneys. Our results point to a pathogenic role of ANCA in WG, and confirm the importance of the idiotypic network in the etiopathogenesis of autoimmune conditions.
Animals↗