Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1674521 | Defective neutrophil function in the autoimmune mouse strain MRL/lpr. Potential role of tr | 1991 Jun 1 | Patients with systemic autoimmune diseases such as SLE and rheumatoid arthritis have increased rates of morbidity and mortality caused by infection. Although this increased risk of infection has been primarily attributed to therapeutic immuno-suppression, some reports exist of defective polymorphonuclear leukocytes (PMN) function in these patients. The purpose of the present work is to investigate the recruitment of PMN phagocytic function in a murine model of autoimmunity, the MRL/lpr mouse. PMN from MRL/lpr, but not from congenic MRL/n mice, exhibit a marked defect in the amplification of FcR-mediated phagocytosis stimulated by various inflammatory mediators. This defect is acquired and correlates with the onset of the autoimmune disease observed in this strain. In addition, MRL/lpr but not MRL/n PMN exhibit a defect in extravasation into the thioglycollate-inflamed peritoneum. Incubation of MRL/n PMN in MRL/lpr serum induces a defect in the amplification of PMN phagocytic function identical to that observed with MRL/lpr PMN. The activity in the serum that induces this defect is neutralized by an antibody to TGF-beta but not by control antibodies. Incubation of murine and human PMN with purified TGF-beta induces an identical defect in stimulated FcR-mediated ingestion. In addition, TGF-beta-treated MRL/n PMN fail to extravasate into the thioglycollate-inflamed peritoneum after injection into normal MRL/n recipient mice. In addition, direct injection of TGF-beta into MRL/n mice also reduces the percentage and number of PMN in the thioglycollate-stimulated peritoneal exudates of these mice. The defect in PMN extravasation and phagocytic function was not caused by failure of the defective PMN to modulate the expression of the adhesion molecules, Mac-1 and Mel-14. These data indicate that defects in PMN function can be observed in a murine model of autoimmunity and that spontaneous production of TGF-beta possibly may play a crucial role in the pathogenesis of the defective PMN function in this animal model. | |
| 1908631 | Omega-3 fatty acids in health and disease and in growth and development. | 1991 Sep | Several sources of information suggest that man evolved on a diet with a ratio of omega 6 to omega 3 fatty acids of approximately 1 whereas today this ratio is approximately 10:1 to 20-25:1, indicating that Western diets are deficient in omega 3 fatty acids compared with the diet on which humans evolved and their genetic patterns were established. Omega-3 fatty acids increase bleeding time; decrease platelet aggregation, blood viscosity, and fibrinogen; and increase erythrocyte deformability, thus decreasing the tendency to thrombus formation. In no clinical trial, including coronary artery graft surgery, has there been any evidence of increased blood loss due to ingestion of omega 3 fatty acids. Many studies show that the effects of omega 3 fatty acids on serum lipids depend on the type of patient and whether the amount of saturated fatty acids in the diet is held constant. In patients with hyperlipidemia, omega 3 fatty acids decrease low-density-lipoprotein (LDL) cholesterol if the saturated fatty acid content is decreased, otherwise there is a slight increase, but at high doses (32 g) they lower LDL cholesterol; furthermore, they consistently lower serum triglycerides in normal subjects and in patients with hypertriglyceridemia whereas the effect on high-density lipoprotein (HDL) varies from no effect to slight increases. The discrepancies between animal and human studies most likely are due to differences between animal and human metabolism. In clinical trials eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of fish oils along with antirheumatic drugs improve joint pain in patients with rheumatoid arthritis; have a beneficial effect in patients with ulcerative colitis; and in combination with drugs, improve the skin lesions, lower the hyperlipidemia from etretinates, and decrease the toxicity of cyclosporin in patients with psoriasis. In various animal models omega 3 fatty acids decrease the number and size of tumors and increase the time elapsed before appearance of tumors. Studies with nonhuman primates and human newborns indicate that DHA is essential for the normal functional development of the retina and brain, particularly in premature infants. Because omega 3 fatty acids are essential in growth and development throughout the life cycle, they should be included in the diets of all humans. Omega-3 and omega 6 fatty acids are not interconvertible in the human body and are important components of practically all cell membranes. Whereas cellular proteins are genetically determined, the polyunsaturated fatty acid (PUFA) composition of cell membranes is to a great extent dependent on the dietary intake.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 1909859 | Genetics of diabetes. Genes and environment. | 1991 Jun | Many other autoimmune and chronic diseases exhibit marked geographic variation in incidence, which has been attributed to environmental differences across populations (Hutt and Burkitt, 1986). The results of our international IDDM research have provided evidence for the importance of large genetic variations in the frequency of HLA susceptibility genes between racial groups and countries. One may speculate that differences in the prevalence of susceptibility genes for other chronic diseases exist and significantly contribute to the geographic patterns of incidence of these disorders. Other autoimmune diseases are known to have epidemiological features similar to those described for IDDM. Although they are also characterized by an underlying HLA-related susceptibility, environmental factors are known to play an important aetiological role (Tiwari and Terasaki, 1985). DNA polymorphisms of the DR, DQ and DP locus antigens are associated with various autoimmune diseases (Todd et al, 1988; Thorsby et al, 1989). These molecular variations are similar to those described for IDDM, in that they are typically related to the hypervariable regions of the molecule and, thus, affect the peptide binding ability of the antigen. Based on the evidence for IDDM, population differences in the frequency of other HLA susceptibility genes are likely to be major determinants of the geographic distribution of diseases such as rheumatoid arthritis and multiple sclerosis. The epidemiological approach outlined in this review is, thus, applicable to other autoimmune diseases and will significantly contribute to our knowledge of the aetiology of these disorders. The emerging field of molecular epidemiology represents a new research approach which will lead to a better understanding of the relationships between specific risk factors and the aetiology of chronic diseases within populations and across the world. | |
| 3660409 | The mechanism of acute cytotoxicity of triethylphosphine gold(I) complexes. II. Triethylph | 1987 Sep 30 | Triethylphosphine gold complexes have therapeutic activity in the treatment of rheumatoid arthritis. Many of these compounds are also highly cytotoxic in vitro to a variety of tumor and non-tumor cell lines. Triethylphosphine gold chloride (TEPAu) is highly cytotoxic to isolated rat hepatocytes at concentrations greater than 25 microM. The earliest changes that could be detected in hepatocytes included bleb formation in the plasma membrane, alterations in the morphology of mitochondria, and rapid decreases in cellular ATP and oxygen consumption. The degradation of ATP could be followed sequentially through ADP and AMP and was ultimately accounted for entirely as xanthine. The sum of adenine and xanthine-derived nucleotides remained constant throughout the experiments. TEPAu (50 microM) caused a significant decrease in the hepatocyte ATP/ADP ratio and energy charge within 5 min. The antioxidant, N,N'-diphenyl-p-phenylenediamine (DPPD), which blocked TEPAu-induced malondialdehyde formation but not cell death, also had no effect on the decreases in oxygen consumption, ATP, ATP/ADP ratio, or energy charge. In isolated rat liver mitochondria, TEPAu (1 microM) caused significant reductions in carbonyl cyanide-4-trifluoromethoxyphenylhydrazone (FCCP) (uncoupled)-stimulated respiration. TEPAu (5 microM) inhibited state 3 respiration and the respiratory control ratio without affecting state 4 respiration and caused a rapid dissipation of the mitochondrial-membrane hydrogen-ion gradient (membrane potential). Concentrations greater than 5 microM also inhibited state 4 respiration. TEPAu caused a concentration-dependent inhibition of FCCP-stimulated respiration with pyruvate/malate and succinate as substrates but had not effect on ascorbate/tetramethyl-p-phenylenediamine-supported respiration. The inhibition of state 4 respiration and FCCP-stimulated respiration by TEPAu (10 microM) could be reversed by the addition of 2 mM dithiothreitol. Dithiothreitol also partially protected cells from TEPAu-induced injury and reversed the TEPAu-induced depletion in cellular ATP. These data indicate that TEPAu may be acting functionally as a respiratory site II inhibitor, similar to antimycin. The reversal of TEPAu-induced inhibition of mitochondrial respiration and cell lethality by dithiothreitol suggests that mitochondrial thiols may be involved. | |
| 1900689 | Effects of lobenzarit disodium on human endothelial cells. Lobenzarit disodium inhibits pr | 1991 Mar | The therapeutic action of lobenzarit disodium (CCA) on the function of endothelial cells (EC) isolated from human umbilical cord veins was investigated. CCA suppressed 3H-thymidine incorporation into EC in a dose-dependent manner. Significant inhibition was detected at a concentration of 50 micrograms/ml. The expression of HLA-DR antigen on the surface of EC was increased when EC were cultured with recombinant interferon-gamma (rIFN gamma). Treatment of EC with either IFN gamma or interleukin-1 enhanced the adhesion of T cells to EC. The kinetics of HLA-DR antigen expression by EC cultured with IFN gamma was different from the kinetics of T cell-EC adhesion, however. Neither anti-HLA-DR nor anti-HLA-ABC monoclonal antibody inhibited T cell binding to EC monolayers. CCA suppressed the expression of HLA-DR antigen by EC cultured with rIFN gamma. In an EC monolayer adhesion assay, CCA also inhibited T cell adhesion to EC in the presence of either IFN gamma or interleukin-1. Significant inhibition was observed at a CCA concentration of 10 micrograms/ml, a level that is easily attainable in serum. These results suggest that CCA may suppress rheumatoid synovitis by reducing the angiogenesis and emigration of chronic inflammatory cells from the blood into the synovium. | |
| 3140819 | Low-dose gold compounds inhibit fibroblast proliferation and do not affect interleukin-1 s | 1988 Oct | We examined the effect of low concentrations of gold compounds on the proliferation of human fibroblasts. Gold sodium thiomalate (GST) inhibited both basal and interleukin-1-induced tritiated thymidine incorporation into fibroblasts in a dose- and time-dependent manner. Significant inhibition was observed at the level of 5 micrograms/ml GST, and greater than 50% inhibition was attained at 10 micrograms/ml. These concentrations are attainable in the serum of treated patients. Similar inhibition was observed when less than 1 micrograms/ml auranofin, which is also within a serum-attainable range, was added. Low concentrations of GST (0-10 micrograms/ml) did not affect interleukin-1 secretion from lipopolysaccharide-stimulated human mononuclear phagocytes (M phi) when assessed by both human fibroblast and C3H/HeJ mouse thymocyte proliferation assays. When M phi precultured for 48 hours with GST (0-10 micrograms/ml) were added to the fibroblast culture in the presence or absence of lipopolysaccharide, there was no significant inhibition of M phi-induced DNA synthesis of fibroblasts. In contrast, when fibroblasts were precultured with GST (0-10 micrograms/ml) for 48 hours and freshly separated M phi were added, significant inhibition was observed in M phi-induced fibroblast proliferation at 5 micrograms/ml. These results suggest that low concentrations of GST directly cause a reduction of fibroblast proliferation, but do not affect the capability of M phi for induction of fibroblast proliferation. Therefore, gold compounds may play a role in the inhibition of the growth of rheumatoid pannus by direct inhibition of fibroblast proliferation. | |
| 1846871 | Glucocorticoid receptor mediated inhibition of interleukin-1 stimulated neutral metallopro | 1991 Feb | Glucocorticoids play an important role in the therapy of arthritic diseases. We sought, firstly, to identify, characterize and localize glucocorticoid receptors (GR) in normal human chondrocytes and, secondly, to determine whether glucocorticoid suppression of human recombinant interleukin-1 beta (rhIL-1 beta)-stimulated metalloproteases (MPs) synthesis by chondrocytes requires GR occupancy. Radioligand binding studies with cultured chondrocytes revealed the presence of high affinity-low capacity [3H]dexamethasone (DEX) binding sites with the following kinetic parameters: Kd = 12.5 +/- 1.4 nmol/L, Nmax = 57,560 +/- 3,960 sites per cell. Competition studies indicated that the DEX binding site was glucocorticoid specific and the competitive hierarchy established was: DEX greater than RU-26988 greater than RU-486 greater than cortisol greater than progesterone much greater than testosterone greater than estradiol-17 beta. Immunocytochemical studies using a specific anti-human GR antiserum identified immunoreactive material primarily in the cytoplasm with cells cultured in the absence of glucocorticoids. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis-Western immunoblotting analysis of chondrocyte cytosol detected the presence of a macromolecular species comigrating with a standard protein possessing a molecular weight of 94 kilodalton. rhIL-1 beta provoked the synthesis and secretion of the MPs stromelysin and collagenase from human chondrocytes in a saturable, coordinate, and dose-dependent fashion. DEX and cortisol inhibited the cytokine-stimulated MP synthesis in similar dose-dependent fashions: DEX, IC50 for stromelysin and collagenase suppression was 1.12 X 10(-8) mol/L and 1.26 X 10(-9) mol/L, respectively and the IC50 for cortisol was 6.3 X 10(-7) mol/L and 4.9 X 10(-8) mol/L, respectively. rhIL-1 beta failed to stimulate metalloprotease synthesis and release from chondrocytes pretreated with 10 nmol/L DEX, even after 20 days of incubation. The antiglucocorticoid, RU-486 completely reversed the DEX induced suppression of MP synthesis at 10(-7) mol/L. RU-486 alone had no effect on MP synthesis. We believe there is a biochemical rationale for the therapeutic efficacy of glucocorticoid administration in the management of arthritic diseases such as osteoarthritis and rheumatoid arthritis, and cytokines such as IL-1 are likely to be involved in the increase in MP synthesis. | |
| 2644350 | Analysis of human IgG and IgA subclass antibody-secreting cells from localized chronic inf | 1989 Feb 15 | The chronic inflammatory diseases in humans have been intensively investigated, however the immune mechanisms underlying diseases such as rheumatoid arthritis (RA), inflammatory bowel disease, and periodontal disease (PD) remain elusive. In this study, we have analyzed the distribution of IgM, IgG, and IgA secreting cells with emphasis on the IgG and IgA subclasses among mononuclear cell populations isolated from gingiva at different stages of PD. Surgically removed tissues were treated with Dispase to gently dissociate cells and the Ficoll-Hypaque gradient centrifugation was used to enrich for viable mononuclear cells rich in lymphocytes, macrophages, and plasma cells. The total numbers of plasma cells increased with the severity of disease. Immunofluorescence analysis showed that most Ig-containing cells were of the IgG isotype; however, significant numbers of IgA-positive cells but few IgM-positive cells were seen. This isolation procedure allowed analysis, at the single cell level, of the distribution of IgG and IgA subclasses of antibody-secreting cells with monoclonal antibodies to human IgG and IgA subclasses. For this, we selected four monoclonal anti-IgG subclass (anti-gamma 1, -gamma 2, -gamma 3, and -gamma 4) antibodies with no subclass cross reactivity for use in the enzyme-linked immunospot assay. Analysis of slight, moderate, and advanced stages of PD showed a progressive increase in spotforming cells (SFC) numbers, and the major isotype of SFC was IgG followed by IgA. The major IgG subclass SFC seen was IgG1 followed by IgG2 whereas similar numbers of IgG3 and IgG4 SFC were observed, a pattern also seen with cells from synovium of RA patients and in mitogen-triggered spleen and PBMC. In terms of the IgA subclass distribution, IgA1 predominated in moderate stages, whereas a selective increase in IgA2 SFC were seen in the more advanced stage of PD. These results show that significant numbers of viable plasma cells/Ig-secreting cells can be isolated from inflamed gingival tissues. Further, careful analysis has shown that IgG subclass responses in gingiva are similar to those found in synovia of RA subjects, and in stimulated PBMC and spleen. However, it should be noted that the number of IgG4- and IgA2-secreting cells increased in the advanced stage of PD. | |
| 3290105 | Interaction between human natural anti-alpha-galactosyl immunoglobulin G and bacteria of t | 1988 Jul | Anti-alpha-galactosyl immunoglobulin G (anti-Gal) is a natural antibody present in unusually high amounts in human sera. It constitutes as much as 1% of circulating immunoglobulin G in humans and displays a distinct specificity for the carbohydrate epitope galactosyl alpha(1----3) galactosyl (Gal alpha 1----3Gal). Recently, it has been suggested by various investigators that anti-Gal may be related to some autoimmune phenomena, since marked elevation of its titer was found in sera of patients with autoimmune thyroid disorders, rheumatoid arthritis, glomerulonephritis, and Chagas' disease. In view of the ubiquitous presence of anti-Gal in high titers in humans, throughout life, we hypothesized that, analogous with synthesis of anti-blood group antibodies against bacterial antigens, bacteria within normal intestinal flora may provide constant antigenic stimulation for the synthesis of anti-Gal. This hypothesis would imply that anti-Gal may bind to a variety of bacterial strains of human flora. In the present study, the interaction between affinity chromatography-purified anti-Gal and various bacterial strains was studied. By the use of a direct immunostaining assay and an enzyme-linked immunosorbent assay, anti-Gal was found to interact with a variety of Escherichia coli, Klebsiella, and Salmonella strains, some of which were isolates from normal stool. Furthermore, the anti-Gal-binding sites in some strains were found to be present on the carbohydrate portion of bacterial lipopolysaccharides. It is thus suggested that Gal alpha 1----3Gal epitopes in the outer membranes of normal flora enterobacteria may provide a continuous source for antigenic stimulation. Since there is no immune tolerance to the Gal alpha 1----3Gal carbohydrate structure in humans, anti-Gal seems to be constantly produced in response to these enterobacteria. In addition, bacteria which express Gal alpha----3Gal epitopes and which may adhere to various cells mediated binding of anti-Gal to human cell lines. These findings raise the possibility that anti-Gal may damage normal human tissues via inflammatory processes facilitated by bacterial Gal alpha 1----3Gal epitopes. | |
| 2110929 | Nodal and extranodal lymphoproliferative disorders in Sjogren's syndrome: a clinical and i | 1990 May | Sjogren's syndrome (SS) is frequently associated with both reactive and neoplastic lymphoproliferative disease. Over a 12-year period beginning in 1970, 21 of 138 patients with SS followed at two tertiary university medical centers had biopsies taken of enlarged lymph nodes (18) or extranodal lymphoid infiltrates (8). Many had immunologic studies performed on fresh tissue and all had paraffin-embedded tissue available for histochemical and immunoperoxidase studies. Eight of our patients had malignant lymphomas which were chiefly B cell neoplasms including two lymphoplasmacytic lymphomas and two follicular center cell lymphomas. The remaining 13 patients had either reactive adenitis (usually with follicular hyperplasia) or atypical lymphoid hyperplasia which failed to meet both histopathologic and immunopathologic criteria for malignancy. None of the nine patients with reactive hyperplasia has yet progressed to lymphoma, while one of four patients with atypical lymphoid hyperplasia progressed to overt lymphoma. Clinical features such as age, duration of disease, extent of lymphadenopathy, splenomegaly, or parotid swelling failed to identify those subsets of patients with lymphadenopathy at increased risk for lymphoma. Recognition of lymphoma in two patients was greatly facilitated by tissue immunologic studies demonstrating focal areas of monotypic B cell proliferation. In one patient in whom the histopathologic diagnosis was immunoblastic sarcoma of B cells, tumor cells were L26-negative and strongly UCHL1-positive suggesting T cell differentiation. In three patients with relatively homogeneous extranodal lymphoid infiltrates, B cell polyclonality on tissue immunoperoxidase studies, and the absence of cytologic atypia, precluded a diagnosis of malignant lymphoma; none of these three patients has progressed to overt lymphoma. Our results indicate that (1) patients with SS develop a variety of B cell lymphomas and other lymphoproliferative disorders, and (2) the nature of the lymphoproliferative disorder is best determined by multiparameter analysis including immunologic phenotyping. | |
| 2948746 | Periductal lymphocytic infiltrates in salivary glands in myasthenia gravis patients lackin | 1986 Oct | In eight of eleven patients with clinical and serological evidence of myasthenia gravis (MG), immunohistological analysis of biopsies from labial salivary glands (LSG) showed focal periductal lymphocytic infiltrates, mainly composed of anti-Leu 3a+ T helper lymphocytes, a finding usually regarded as indicative for Sjögren's syndrome (SS). None of the patients could however, according to functional criteria, be considered as having SS. This study thus indicates that lymphocytic infiltrates in LSG can be seen in MG, which has been thought of as an organspecific autoimmune disease with symptoms and signs confined to striated muscles. | |
| 3092835 | Expression of histocompatibility antigen HLA-DR by salivary gland epithelial cells in Sjö | 1986 Sep | Recent studies have suggested that the induction of HLA-DR antigens on epithelial cells plays an important role in the pathogenesis of autoimmune endocrine-exocrine disorders. We found that salivary gland epithelial cells (i.e., acinar and ductal cells) in salivary gland biopsy specimens from patients with primary Sjögren's syndrome (keratoconjunctivitis sicca) expressed high levels of HLA-DR antigen, which were detected by staining frozen tissue sections with monoclonal antibodies and immunoperoxidase technique. In contrast, salivary gland epithelial cells from normal subjects did not express this antigen. Lymphocytes eluted from the salivary gland biopsy specimens of patients who had Sjögren's syndrome produced a soluble factor that stimulated HLA-DR synthesis by a salivary gland-derived cell line (Sal-1). These tissue culture supernatants contained gamma-interferon, and their ability to induce HLA-DR synthesis was blocked by monoclonal anti-gamma-interferon antibody. These results demonstrate the presence of HLA-DR antigen on salivary gland epithelial cells and suggest that local production of gamma-interferon plays a role in this induction. | |
| 2945683 | In vitro autoantibody synthesis by anti-La(SSB) positive SLE patients and healthy controls | 1986 Jul | In vitro production of anti-La(SSB) and anti-DNA antibodies by mononuclear cells (mnc) from systemic lupus erythematosus (SLE) patients and healthy controls was measured using ELISA techniques. The SLE patients were divided into anti-La(SSB) positive and negative groups depending on Ouchterlony analysis of the serum. Both patient groups spontaneously produced raised levels of total IgG but not IgM compared to controls. Pokeweed mitogen (PWM) stimulated mnc from anti-La(SSB) positive SLE patients and controls gave good total IgM and IgG responses. In contrast the anti-La(SSB) negative group gave no IgG but did make an IgM response. Kinetic studies showed that 14 day cultures were essential to produce detectable amounts of specific autoantibodies which, with a few exceptions, were of IgM isotype. Low levels of anti-La(SSB) and anti-DNA were spontaneously produced by anti-La(SSB) positive SLE patients and controls. PWM stimulation at least doubled autoantibody synthesis in these two groups. The anti-La(SSB) negative SLE group gave similar responses although PWM induced autoantibody levels were reduced. ConA-induced suppressor cell assay showed that anti-La(SSB) positive SLE patients could form suppressor cells but not as effectively as controls. This group of SLE patients were more successful at suppressing IgG than IgM responses. | |
| 2739151 | Sjögren's syndrome following gastrectomy and chemotherapy for gastric malignant lymphoma. | 1989 May | The case of a 72-year-old man who developed Sjögren's syndrome three years following gastrectomy and chemotherapy for gastric malignant lymphoma is reported. The patient eventually died of systemic cryptococcal infection, and autopsy revealed no recurrence of the malignant lymphoma. Review of the literature indicates lymphoproliferative disease preceding the development of Sjögren's syndrome is extremely rare. | |
| 3071327 | A phase I study of therapy with recombinant granulocyte-macrophage colony-stimulating fact | 1988 Aug | Sixteen patients with primary or secondary bone marrow failure were treated with recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) given as either an intravenous bolus or by continuous infusion. The dose range studied was from 15 micrograms/m2/d to 960 micrograms/m2/d. Administration of rGM-CSF on a bolus schedule failed to elicit a hematologic response, but resulted in side effects of epigastric distress and eructation in over 30% of administered courses. Administration of rGM-CSF by continuous infusion resulted in a dose-dependent increase in the total leukocyte, granulocyte, and eosinophil counts. The mean maximal rise in granulocyte count was 8.5-fold. After cessation of therapy, blood counts returned to near baseline in most patients by 7 days. A 36 percent decrease from baseline in mean serum cholesterol level was observed in the continuous infusion group, but not in patients receiving rGM-CSF as an IV bolus. Fever, fatigue, and bone pain were dose-limiting in the continuous infusion group at a dose of 240 micrograms/m2/d. The maximally tolerated dose was 480 micrograms/m2/d. No life-threatening toxicities were observed in either group. Our data demonstrate that continuous infusion rGM-CSF is biologically active and non-toxic at a dose of 120 micrograms/m2/d in patients with bone marrow failure. | |
| 3491773 | Nature of immune complexes in autoimmune chronic active hepatitis. | 1987 Feb | Immune complexes containing antinuclear antibodies have been observed in autoimmune chronic active hepatitis. Using a library of nuclear constituents (deoxyribonucleic acid, small nuclear ribonucleoproteins, and histones), we analyzed the antigens involved in formation of immune complexes. Immune complexes were defined in dissociation experiments, and after separation under dissociating conditions. Immune complexes composed of histones and immunoglobulin G were observed in four of nine immune complex-positive autoimmune chronic active hepatitis sera. Immune complexes containing the small nuclear ribonucleoprotein U1-RNP and immunoglobulin G were observed in two additional samples. Kidney eluates obtained from 2 patients with autoimmune chronic active hepatitis and membranous glomerulonephritis revealed enrichment of anti-U1-RNP, suggesting specific deposition of this antibody in complexed form. Circulating immune complexes containing histones were observed only in patients with autoimmune chronic active hepatitis-associated sicca syndrome; those containing U1-RNP were restricted to patients with autoimmune chronic active hepatitis associated with kidney disease. | |
| 2420510 | Recent advances in laboratory tests and the significance of autoantibodies to nuclear anti | 1986 Mar | There are many types of ANA and they may react with different nuclear components varying from nucleic acids to both basic and acidic nuclear proteins. Recent investigations have demonstrated that it is important not only to detect the presence and quantity of the ANA, but also to identify the immunologic specificities of the ANA in a given patient. The specific identification of the immunologic specificity of the ANA helps in the diagnosis and management of therapy in the various rheumatic diseases. In recent years, much progress has been made in the improvements of sensitivity, specificity, and quality control of many of the clinical laboratory tests for detection and quantitation of ANAs. Distinct profiles of ANA characterize different rheumatic diseases. A number of ANAs are found in SLE, whereas other diseases are characterized by the presence or absence of a certain ANA or by differences in mean ANA titers. Specific ANAs have been used to isolate and characterize nuclear antigens at the molecular and functional levels. | |
| 1965021 | Mononuclear cell phenotypes and immunoglobulin gene rearrangements in lacrimal gland biops | 1990 Dec | Immunocytochemical studies of lacrimal gland biopsies obtained from eight patients with Sjögren's syndrome revealed the major component of the mononuclear cell infiltrates to be comprised of B cells and Leu-3+ T-helper cells, which were present well in excess of control glands. Three of seven cases that were tested harbored cells that stained with monoclonal antibodies against different components of Epstein-Barr virus (EBV); one of the biopsies also contained cells that bore cytomegalovirus antigens. Immunoglobulin-gene rearrangements, but not T-cell receptor rearrangements, were demonstrated in one of two Sjögren's lacrimal gland biopsies tested. The authors conclude that the destruction of the tubuloacinar architecture of lacrimal gland tissue in Sjögren's syndrome appears secondary to lymphoproliferation of B cells and T-helper cells, probably derived from primary lymphoid follicles. Productive infection of lacrimal gland tissue with EBV may play a role in the pathogenesis of the syndrome in selective cases. | |
| 1698806 | Polyclonal human rheumatoid factors cross-reacting with histone H3: characterization of an | 1990 Jul | The development of highly sensitive immunoassays has made the detection of the multireactivity of antibodies a relatively common phenomenon. Polyreactivity is frequent in human auto antibodies, especially in rheumatoid factors (RFs), but the structural basis and the significance of this phenomenon remain substantially unknown. Recently, we showed that the double reactivity of a human monoclonal RF with histones was probably due to two distinct binding sites. However, cross-reactivity seems more frequent among polyclonal RFs occurring during autoimmune diseases than with monoclonal RFs. We studied double-reactive (IgG and histone H3) polyclonal RFs in a patient suffering from primary Sjögren's syndrome. We showed by means of affinity chromatographies that H3 cross-reactive RFs were only a small subset of the total patient's RFs and that this subset was enriched in IgA class. Competitive inhibition experiments suggested the existence of two distinct binding sites for IgG and H3. These results were confirmed by showing the selective sensitivity to acid treatment of the histone binding site and by producing a murine antiidiotope monoclonal antibody BII 2.1 defining an idiotope on bireactive RF apparently linked to the H3 binding site. This idiotope was absent in a panel of monoclonal RF, one of them cross-reacting with histone H3. This report extends previous results concerning a monoclonal RF to the polyclonal RFs which occur during autoimmune diseases. | |
| 3486064 | Idiotypes on antibodies to the La (SS-B) antigen are restricted and associated with the an | 1986 Feb | Rabbit anti-idiotypic antibodies were prepared against affinity purified autoantibodies to the ribonucleoprotein La (SS-B) antigen from the sera of three unrelated patients. Each anti-idiotype recognized private idiotypes expressed only on the immunizing anti-La antibody. In each case they were conformationally dependent and related to the antigen binding site. This demonstration of immunodominant private idiotypes on human autoantibodies to ribonucleoproteins is in direct contrast to the cross-reactive idiotypes described on rheumatoid factors and autoantibodies to DNA. We discuss the possibility that anti-La antibodies, unlike anti-DNA, arise as a result of autoantigenic stimulation. |