Ann H. McDonald , Michelle Schneider , Lynn Gudenkauf , James R. Sanger , Kimberly Weir
{"title":"Silicone Gel Enhances the Development of Autoimmune Disease in New Zealand Black Mice but Fails To Induce It in BALB/cAnPt Mice","authors":"Ann H. McDonald , Michelle Schneider , Lynn Gudenkauf , James R. Sanger , Kimberly Weir","doi":"10.1006/clin.1998.4532","DOIUrl":"10.1006/clin.1998.4532","url":null,"abstract":"<div><p>Anecdotal evidence links silicone gel breast implants with the development of autoimmune connective tissue disease in women. To investigate whether silicone gel is capable of directly inducing and/or enhancing the development of autoimmune disease, female BALB/cAnPt (BALB/c) and New Zealand Black (NZB) mice were injected subcutaneously with silicone gel, pristane, a nonmetabolizable substance that can cause plasmacytomas in BALB/c and NZB mice, or saline and monitored for the development of glomerulonephritis and autoantibody production. NZB, but not BALB/c, mice spontaneously develop autoantibodies and an autoimmune hemolytic anemia by 12 months of age. Over a period of 10 months, biweekly screening for proteinuria revealed increases in urinary protein in NZB mice that received multiple injections of either silicone gel or pristane. In contrast, urinary protein was unaffected in identically treated BALB/c mice. Although, silicone gel had no effect on serum titers of anti-erythrocyte antibodies in NZB mice, the hematocrits were significantly decreased. Moreover, silicone gel both increased the concentration of IgM anti-type I collagen antibodies and skewed the immunofluorescent staining pattern of serum autoantibodies on HEp-2 cells. In contrast, silicone gel failed to induce the production of anti-erythrocyte or antinuclear antibodies in BALB/c mice and induced only slight increases in IgG anti-type I collagen antibodies. These results suggest that silicone gel can exacerbate the development of autoimmune disease in autoimmune NZB mice, but fails to induce disease in normal BALB/c mice. This is consistent with several epidemiological studies failing to demonstrate an increase in the incidence of autoimmune disease in women with breast implants. However, because silicone gel was able to exacerbate autoimmune disease in NZB mice, it may play a similar role in the development of autoimmune disease in a small percentage of women who are genetically susceptible to such diseases.</p></div>","PeriodicalId":10683,"journal":{"name":"Clinical immunology and immunopathology","volume":"87 3","pages":"Pages 248-255"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/clin.1998.4532","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20564841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell Death and Oxidative Damage in Inflammatory Myopathies","authors":"Dominique S. Tews, Hans H. Goebel","doi":"10.1006/clin.1998.4527","DOIUrl":"10.1006/clin.1998.4527","url":null,"abstract":"<div><p>There is evidence that muscle fibers in denervating disorders and muscular dystrophies undergo apoptosis. In 21 patients with autoimmune inflammatory myopathies, we found no features of muscle fiber apoptosis such as DNA fragmentation or expression of apoptosis-related proteins. However, muscle fibers in myositis displayed distinct up-regulation of inducible and neuronal nitric oxide synthase (NOS). While inducible NOS was distinctly up-regulated on the sarcolemma of all kinds of muscle fibers neuronal NOS displayed increased expression in the sarcoplasm of damaged as well as atrophic muscle fibers. There were no disease-specific patterns in the different myositis subtypes. Enhanced expression of NOS with production of nitric oxide may contribute to oxidative stress mediating muscle fiber damage and muscle fiber necrosis representing the predominant cell death mechanism in myositis. Nevertheless, inflammatory cells displayed numerous DNA-fragmentation-positive nuclei and expression of apoptosis-related proteins indicating that apoptosis plays a role in the regulation of the inflammatory cellular response.</p></div>","PeriodicalId":10683,"journal":{"name":"Clinical immunology and immunopathology","volume":"87 3","pages":"Pages 240-247"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/clin.1998.4527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20564840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Association Between Anti-Ribosomal P Antibodies and Active Nephritis in Systemic Lupus Erythematosus","authors":"Vishala Chindalore, Barbara Neas, Morris Reichlin","doi":"10.1006/clin.1998.4541","DOIUrl":"10.1006/clin.1998.4541","url":null,"abstract":"<div><p>Autoantibodies to anti-ribosomal P protein have been recognized in patients with systemic lupus erythematosus (SLE) in widely variable proportions of unselected patients. Presence of anti-ribosomal P antibodies was retrospectively studied in 69 patients with SLE during disease exacerbations and remissions or during continuously active disease. Anti-ribosomal P antibodies were positive in 21/69 patients during active disease, with an overall prevalence of 30.4%. Prevalence in patients with active nephritis was 75.0% (15/20),<em>P</em>value by Fisher's exact test of 8.39 × 10<sup>−7</sup>. In 12/13 patients (92.3%), anti-P disappeared during periods of disease remission,<em>P</em>= 0.0002. In 17/21 patients (81.0%) with anti-ribosomal P antibodies, anti-dsDNA antibodies were also positive. In 47 patients without anti-P, 23/47 (48.9%) were also positive for anti-dsDNA. In 9/12 patients (75.0%) titers of anti-dsDNA antibodies correlated with anti-P during disease exacerbations and remissions,<em>P</em>= 0.004. The higher prevalence of anti-P in patients with lupus nephritis with disappearance during disease remissions supports the hypothesis of an immunopathogenetic role of these antibodies in lupus nephritis. There was also a strong association between anti-dsDNA and anti-P antibodies.</p></div>","PeriodicalId":10683,"journal":{"name":"Clinical immunology and immunopathology","volume":"87 3","pages":"Pages 292-296"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/clin.1998.4541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20565399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriel Morón, Belkys Maletto, Andrea Rópolo, Marı́a Cristina Pistoresi-Palencia
{"title":"Effect of Aging on Experimental Autoimmune Prostatitis: Differential Kinetics of Development","authors":"Gabriel Morón, Belkys Maletto, Andrea Rópolo, Marı́a Cristina Pistoresi-Palencia","doi":"10.1006/clin.1998.4534","DOIUrl":"10.1006/clin.1998.4534","url":null,"abstract":"<div><p>We have studied the influence of aging on the kinetics of autoimmune response in Experimental Autoimmune Prostatitis (EAP). EAP was induced in 3- and 12-month-old Wistar rats by i.d. immunization with a saline extract of rat male sex accesory glands (RAG), chemically modified, and emulsioned in CFA. After immunization, 12-month-old rats developed a faster and stronger specific DTH response against RAG and mononuclear infiltration in the prostate. The levels of total IgM and IgG against RAG were lower in 12-month-old rats than in 3-month-old rats, with a prevalence of IgG2a, IgG2b, and IgG2c subclasses in both ages. Immunization stimulated slightly the appearance of specific IgG1 to RAG only in 3-month-old rats but in 12-month-old rats there was no specific IgG1 to RAG. On the other hand, normal 12-month-old rats showed higher levels of some natural antibodies and their thymocytes and peripheral lymphocytes had a diminished proliferative capacity compared to 3-month-old rats. These data demonstrated that 12-month-old rats show parameters of an aged immune system and present an exacerbated autoimmune prostatitis compared with 3-month-old rats.</p></div>","PeriodicalId":10683,"journal":{"name":"Clinical immunology and immunopathology","volume":"87 3","pages":"Pages 256-265"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/clin.1998.4534","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20564842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Silicone Gel and Animal Models of Autoimmune Disease","authors":"Kimber L. White Jr.","doi":"10.1006/clin.1998.4567","DOIUrl":"10.1006/clin.1998.4567","url":null,"abstract":"","PeriodicalId":10683,"journal":{"name":"Clinical immunology and immunopathology","volume":"87 3","pages":"Pages 205-206"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/clin.1998.4567","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20564835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tunhan Chang, Saurabh Chowdhry, Priya Budhu, Richard R. Kew
{"title":"Smokeless Tobacco Extracts Activate Complementin Vitro:A Potential Pathogenic Mechanism for Initiating Inflammation of the Oral Mucosa","authors":"Tunhan Chang, Saurabh Chowdhry, Priya Budhu, Richard R. Kew","doi":"10.1006/clin.1998.4530","DOIUrl":"10.1006/clin.1998.4530","url":null,"abstract":"<div><p>The use of smokeless tobacco has been linked to an increased incidence of inflammation of the buccal and gingival mucosa. However, the mechanisms by which smokeless tobacco initiates inflammation are not well understood. The complement cascade is a ubiquitous source of proinflammatory molecules and can be activated rapidly by a wide variety of agents. Therefore, the effect of smokeless tobacco on complement was investigated as a potential pathogenic mechanism for triggering inflammation of the oral mucosa. Aqueous extracts of loose leaf chewing tobacco (1S1), dry snuff (1S2), and moist snuff (1S3), added to normal human serum, depleted complement hemolytic activity in a dose-dependent manner. Experiments utilizing sera deficient in one specific complement component indicated that the smokeless tobacco-induced depletion of hemolytic activity was due largely to consumption of C3. Furthermore, assays designed to test the activity of the alternative pathway of complement clearly showed that all three extracts depleted the hemolytic activity of this pathway. Finally, all three smokeless tobacco extracts activated the alternative pathway since significantly elevated levels of the cleavage fragments iC3b and Bb were detected in extract-treated serum. High quantities of the classical pathway cleavage fragment C4d also were detected in serum treated with moist snuff (1S3). The results clearly demonstrate that smokeless tobacco extracts activate the alternative pathway and also suggest some measure of classical pathway activation. Activation of complement by smokeless tobacco may be a mechanism for initiating inflammation of the oral mucosa.</p></div>","PeriodicalId":10683,"journal":{"name":"Clinical immunology and immunopathology","volume":"87 3","pages":"Pages 223-229"},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/clin.1998.4530","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20564838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivan R. Romero , Carol Morris , Monica Rodriguez , Terry W. Du Clos , Carolyn Mold
{"title":"Inflammatory Potential of C-Reactive Protein Complexes Compared to Immune Complexes","authors":"Ivan R. Romero , Carol Morris , Monica Rodriguez , Terry W. Du Clos , Carolyn Mold","doi":"10.1006/clin.1997.4516","DOIUrl":"10.1006/clin.1997.4516","url":null,"abstract":"<div><p>C-reactive protein (CRP) is an acute phase serum protein that binds to phosphocholine (PC) and to components of damaged tissue. CRP resembles antibody in that it binds to ligands and activates the classical complement pathway. To compare the processing of CRP complexes to that of IgG complexes, we have prepared complexes containing the same ligand, PC-conjugated BSA, and IgG antibody to either BSA or CRP. We previously demonstrated similar complement-mediated binding of these complexes to erythrocyte complement receptors. CRP and IgG also bind to receptors on neutrophils (PMN), providing another possible pathway for clearance of ligands. PMN binding of IgG complexes can lead to activation with damaging inflammatory consequences. In the present report we have used CRP and IgG complexes containing PC-BSA to compare binding to PMN and activation of PMN adherence to endothelial cells. The results indicate that CRP complexes do not activate PMN whereas IgG complexes do. Binding assays indicate that there is substantially greater binding of IgG than CRP complexes to PMN.</p></div>","PeriodicalId":10683,"journal":{"name":"Clinical immunology and immunopathology","volume":"87 2","pages":"Pages 155-162"},"PeriodicalIF":0.0,"publicationDate":"1998-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/clin.1997.4516","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20534390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaobing Wu , Bin Liu , Pieter-Luttig Van der Merwe , Neale Nicola Kalis , Seth M. Berney , David C. Young
{"title":"Myosin-Reactive Autoantibodies in Rheumatic Carditis and Normal Fetus","authors":"Xiaobing Wu , Bin Liu , Pieter-Luttig Van der Merwe , Neale Nicola Kalis , Seth M. Berney , David C. Young","doi":"10.1006/clin.1998.4531","DOIUrl":"10.1006/clin.1998.4531","url":null,"abstract":"<div><p>EBV-transformed B cells from a 20-week human fetal spleen and from blood of patients with poststreptococcal rheumatic carditis were studied. Most antibodies from nine fetal and six patient myosin-reactive B cell clones were multireactive (reacting with cardiac myosin,<em>Streptococcus pyogenes,</em>and rat cardiac myocytes) which supports a role for molecular mimicry in stimulation of these autoantibodies. Sequence analysis revealed that fetal and patient anti-myosin repertoires were composed of unrelated clones with diverse V gene usages. Fetal and patient antibodies had reduced V<sub>H</sub>CDR3 length on average and reduced light chain N region addition with a low rate of somatic mutation in the variable region genes, characteristics generally associated with fetal B cells but also with some adult B cells. Five of six myosin-reactive patient clones used V<sub>H</sub>3, whereas only two of nine fetal clones used V<sub>H</sub>3, suggesting skewing from the average 50–60% V<sub>H</sub>3 gene usage found in randomly selected adult and fetal antibodies.</p></div>","PeriodicalId":10683,"journal":{"name":"Clinical immunology and immunopathology","volume":"87 2","pages":"Pages 184-192"},"PeriodicalIF":0.0,"publicationDate":"1998-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/clin.1998.4531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20534350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of TGFβ in the Pathogenesis of Human Tuberculosis","authors":"Zahra Toossi , Jerrold J. Ellner","doi":"10.1006/clin.1998.4528","DOIUrl":"10.1006/clin.1998.4528","url":null,"abstract":"","PeriodicalId":10683,"journal":{"name":"Clinical immunology and immunopathology","volume":"87 2","pages":"Pages 107-114"},"PeriodicalIF":0.0,"publicationDate":"1998-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/clin.1998.4528","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20534384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}