Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1981240 | Phenotypic markers of lymphocyte and mononuclear phagocyte activation within rheumatoid no | 1990 Sep | We investigated rheumatoid subcutaneous nodules using monoclonal antibodies recognizing functional determinants on mononuclear phagocytes (Mph) and lymphocytes. Mph at the center of rheumatoid nodules showed strong expression of the leukocyte intergrins CR3 and p150,95 which would be consistent with the presence of a central chemotactic stimulus. Mph expression of FcR1, a gamma interferon regulated molecule, was decreased in 5/13 cases despite strong expression of MHC class II. There was a variable unstructured infiltrate of T lymphocytes, a majority of which were CD8 positive. Lymphocytes showed increased MHC class II expression but interleukin 2 receptor expression was low. We discerned no relationship between the number, distribution or phenotype of the T cell infiltrate and the phenotype of the predominant Mph population. | |
| 2379935 | [Immunoglobulin and T-cell receptor gene rearrangements in patients with autoimmune diseas | 1990 Jun | Immunoglobulin-(Ig-) and T-cell-receptor-(TcR-)gene rearrangements were investigated in peripheral blood lymphocytes (PBL) of patients with various autoimmune disorders. In patients with SLE there was no predominant Ig- or TcR-gene rearrangement. This was also true in patients with a long disease duration and with excessive hypergammaglobulinemia. These results lead us to suggest that B cells are activated polyclonally in these patients. In those cases, where predominantly rearranged Ig- or TcR-genes were found, the autoimmune disorder was associated with a low-grade non-Hodgkin lymphoma (NHL). This coherence of B-cell malignancy and autoimmunity was only found in patients with cryoglobulinemia (KG), cold agglutinin disease (KA), and hemolytic anemia (AIHA). | |
| 1751318 | Systemic lupus erythematosus, dermatomyositis, scleroderma, vasculopathies, and other conn | 1991 Oct | The diverse disorders discussed in this review share the underlying features of multisystem involvement and vasculitis as a part of their pathophysiology. A review of morbidity seen in childhood-onset systemic lupus erythematosus reveals the need for careful monitoring for complications secondary to treatment and infections. Current understanding of the pathophysiology and risks of developing the neonatal lupus syndrome are reviewed, with the important recognition of the association of specific maternal autoantibodies with affected offspring. A review of current management issues in the treatment of juvenile dermatomyositis is discussed. Kawasaki disease, one of the most common childhood vasculitides, continues to provoke interest in the areas of accurate diagnosis, potential etiologic role of common viruses, management, and late morbidity. Interesting case reports of children with unusual features of the more rarely described disorders of Sjögren's syndrome, scleroderma, and Behçet's syndrome are discussed. | |
| 2789656 | Estrogen induces the development of autoantibodies and promotes salivary gland lymphoid in | 1989 Aug | There are important bidirectional interactions between the immune and the endocrine system. Sex hormones influence the immune system throughout life including postnatal and prenatal stages. For example, we find that administration of estrogen to normal mice markedly augments the ability of CD5+ B cells to express their autoimmune potential by producing increased numbers of plaque-forming cells (APFC) to bromelain-treated mouse erythrocytes (Br-ME). The effect of sex hormones on immune function at the most critical stage of development, the prenatal period, remains unstudied. We hypothesize that an imbalance of the in utero sex hormone microenvironment critically influences the fetal immune system. We have termed this influence immunological imprinting. After birth this imprinting could contribute to immune-mediated disorders. To test this hypothesis, we developed a mouse model in which normal mice were prenatally exposed to estrogens. In preliminary experiments, these mice produced higher numbers of APFC to Br-ME, particularly in the peritoneal cavity cell exudates. Furthermore, mice prenatally exposed to estrogens had accelerated development of autoimmune salivary gland lesions indistinguishable from Sjögren's syndrome (SS) in humans. Further experiments are warranted to confirm these findings. The prenatal effects of estrogen may have relevance for familial and neonatal autoimmune syndromes. | |
| 3259714 | Hypergammaglobulinemic purpura of Waldenström. (A report of serologic and immunogenetic s | 1988 Jan | Data from a study carried out on a group of 18 patients with hypergammaglobulinemic purpura of Waldenström (HPW) followed-up for 3-14 years are reported in this paper. In 11 patients the syndrome was considered to be idiopathic, while in the remaining 7 it was associated with Sjögren's syndrome (SS). A marked (17/1) female prevalence was observed. Purpura was the presenting clinical manifestation in 9 patients, but it occurred at different points during the course of the disease; Raynaud's phenomenon was present in one third of patients. Serum gammaglobulin levels were higher than 2.2 g/dl in all the cases and higher than 3 g/dl in 9 cases. Immune complexes were detected in all patients. A significant serologic finding in our case series was represented by the frequency of anti-Ro (16/16) and anti-La (14/15) antibodies, clearly higher than that reported in SS patients. HLA typing showed a marked increase of B8 and DR3 antigens as well as A1,B8,DR3 haplotype, never reported in other autoimmune diseases. On the basis of serologic and immunogenetic features, HPW seems a clearly distinguishable entity among autoimmune vasculitis. | |
| 2963643 | Quantitative defect of CD4+2H4+ cells in systemic lupus erythematosus and Sjögren's syndr | 1987 Dec | Surface antigens of T lymphocytes in peripheral blood mononuclear cells from 19 patients with systemic lupus erythematosus (SLE), 14 patients with Sjögren's syndrome (SS), and 14 healthy control subjects were studied by 2-color analysis. The proportion of CD4+2H4+ cells, which correspond to a suppressor/inducer subset, was decreased significantly in both SLE and SS. In contrast, the percentage of CD4+4B4+ cells, which define a helper/inducer subset, showed no significant difference among the patient groups. These data suggest that quantitative defect of suppressor/inducer cells may play an important role in the immunoregulatory disturbance in SLE and SS. | |
| 3436098 | A common idiotype expressed on a murine anti-Sm monoclonal antibody and antibodies in SLE | 1987 Dec | A rabbit anti-idiotypic antiserum made against a murine monoclonal anti-Sm autoantibody (Y2) was used in a solid-phase radioimmunoassay to investigate idiotypic cross-reactivity among anti-Sm antibodies present in sera from patients with systemic lupus erythematosus. Sera from 25 of 51 SLE patients (49%) containing anti-Sm antibodies were positive for this Y2 idiotype compared to only one of 22 normal human sera. Nine of 28 SLE patients (32%) whose sera were anti-Sm negative were also positive for the Y2 idiotype in low titre. Binding was not due to rheumatoid factor-like activity but was specific for the Y2 determinant and could be eliminated by absorption with Y2 monoclonal antibodies. The anti-idiotypic antibody blocked the ability of 12 of 25 anti-Sm positive lupus sera to bind Sm. Conversely, Sm antigen inhibited the binding of anti-idiotypic antibody in nine of 12 lupus sera. | |
| 3501352 | Class II MHC antigen expression on epithelial cells of salivary glands from patients with | 1987 Jul | Class II MHC molecules are two-chain glycoproteins normally expressed only on the membrane of cells involved in the immune response. These molecules are restriction elements for helper T cells. Using indirect immunofluorescence on cryostat sections of biopsied salivary glands we have demonstrated epithelial expression of class II antigens in patients with Sjögren's syndrome. The HLA DR+ epithelial cells were seen in close proximity to lymphocyte infiltrates. The finding that class II molecules are also expressed in salivary glands without focal lymphocytic infiltrates suggests a "modulation" as opposed to "induction" of HLA DR antigens on epithelial cells in Sjögren's syndrome, the distinction being related to the enhancement of low levels of expressions vs. de novo synthesis. | |
| 1896812 | High prevalence of autoimmune liver disease in patients with multiple nuclear dot, anti-ce | 1991 Jul | We used HEp-2 cells to compare the occurrence of multiple nuclear dot (MND), anti-centromere (ACA), and mitotic spindle antibodies (MSA) in patients with primary biliary cirrhosis (PBC) (n = 32) and primary Sjögren's syndrome (n = 50). The predictive value of these antibodies for autoimmune liver disease was evaluated among patients with chronic liver or inflammatory connective tissue diseases. MND were found in 6%, ACA in 10%, and MSA in 6% of PBC sera. Among patients with primary Sjögren's syndrome, ACA were found in one, whereas another had both MND and MSA. MND were also detected in 1 of 25 sera from patients with other chronic inflammatory connective tissue diseases. Reexamination of these three patients showed evidence of PBC in two. In a blinded study of sera from 356 patients with chronic liver diseases, MND were detected in 10 (3%), ACA in 2 (0.9%), and MSA in 4 (1.2%). All patients with MND or ACA and two of four with MSA had PBC or autoimmune chronic active hepatitis, particularly of the cholestatic type. In four of these patients the liver disease had not previously been classified. We conclude that these antibodies have low sensitivity but high predictive value for autoimmune, cholestatic liver disease. | |
| 1758539 | Selective hypoaldosteronism in a patient with Sjögren's syndrome: insensitivity to angiot | 1991 | A 51-year-old Japanese woman with hypokalemia due to distal renal tubular acidosis associated with Sjögren's syndrome exhibited a decreased plasma aldosterone level despite elevated plasma renin activity. Our studies revealed selective hypoaldosteronism with normal adrenoglucocorticoid function. In the presence of a low level of serum potassium (3.6 mEq/l), plasma levels of deoxycorticosterone and corticosterone were normal, while plasma aldosterone was very low. The levels of these three mineralocorticoids showed only minor changes during infusion of angiotensin II. Furosemide administration under almost the same level of serum potassium (3.7 mEq/l) resulted in only a slight increase of plasma aldosterone. Since hypokalemia might possibly suppress the synthesis of aldosterone in the zona glomerulosa, angiotensin II was also infused under a normal level of potassium (4.3 mEq/l). However, angiotensin II also failed to stimulate any secretion of aldosterone, despite a progressive rise in blood pressure and sufficient suppression of plasma renin activity. On the other hand, rapid ACTH administration in the presence of 4.4 mEq/l of serum potassium increased both plasma aldosterone and cortisol. These results suggest that adrenal insensitivity to angiotensin II was the cause of the selective hypoaldosteronism in our patient, possibly due to a dysfunction of adrenal angiotensin II receptors, a disorder of postreceptors or both. | |
| 1688513 | Characterization of the autoantigen La as a nucleic acid-dependent ATPase/dATPase with mel | 1990 Jan 12 | The autoantigen La, a known transcription termination factor of RNA polymerase III, was purified to homogeneity from mouse 3T3 cells and calf thymus by different isolation procedures. The La protein from calf thymus was separated into RNA binding and nonbinding subclasses. The murine La protein and the RNA binding subclass of calf thymus La protein showed ATPase/dATPase activity in the presence of DNA-RNA or RNA-RNA hybrids. A novel monoclonal anti-La antibody (La11G7) and patients' anti-La antibodies immunoadsorbed to homogeneously purified La protein were able to inhibit the enzyme activity of La protein. La protein was able to melt a synthetic DNA-RNA hybrid in a reaction that required ATP hydrolysis. The RNA binding ability of the nonbinding subclass was restored by treatment with sialidase. This treatment also restored the protein's ATP-dependent melting activity. | |
| 2328434 | Endophthalmitis caused by exogenous nocardial infection in a patient with Sjögren's syndr | 1990 Feb | A 60-year-old woman receiving prednisolone therapy for Sjögren's syndrome presented with corneal perforation. Therapeutic penetrating keratoplasty was performed, but no causative organism was identified. Focal inflammatory infiltrates in both donor and host cornea and anterior uveitis developed postoperatively. Five months later the inflammation rapidly became much worse, with fulminating abscesses, and the eye was eviscerated because of severe endophthalmitis. Nocardia organisms were identified in the cornea, conjunctiva and vitreous by means of acridine orange and modified Ziehl-Neelsen stains. The infection produced both suppurative and granulomatous inflammation. Reexamination of the penetrating keratoplasty specimen with a modified Ziehl-Neelsen stain revealed a few Nocardia organisms, which suggested that infection had occurred at the time of corneal perforation. | |
| 2477002 | A major autoepitope is present on the amino terminus of a human SS-A/Ro polypeptide. | 1989 Aug | A human SS-A/Ro antigen is present on the polypeptide component of a particle composed of hyRNA and a 60 kD protein. We have now purified the Wil-2 cell 60 kilo dalton (kD) SS-A/Ro protein and determined its amino-terminal amino acid sequence. A synthetic peptide corresponding to residues 7 to 24 of this sequence (RoSP7-24) exhibited enzyme-linked immunosorbent assay (ELISA) binding activity with immunodiffusion-defined, monospecific anti-SS-A/Ro sera. In addition, ELISA binding of monospecific anti-SS-A/Ro sera to native SS-A/Ro antigen was partially inhibited (35%) by KLH-RoSP7-24. Sera from patients known to frequently produce precipitating anti-SS-A/Ro antibody (subacute cutaneous lupus erythematosus [SCLE], 56 patients; Sjögren's syndrome [SS], 41 patients; mothers of infants with neonatal LE [NLE], 10 individuals; infants with congenital heart block [CHB], 5 patients) were tested for reactivity to RoSP7-24 in ELISA. Overall, 38% of SCLE sera, 36% of SS sera, 50% of maternal NLE sera and 20% of CHB infant sera had anti-RoSP7-24 binding levels greater than 2 standard deviations above the mean of that of normal individuals. Of the sera which had anti-SS-A/Ro detected by double immunodiffusion and/or counterimmunoelectrophoresis, 68% of SCLE patients, 71% of SS patients, 55% of NLE mothers and 20% of CHB infants had significantly elevated RoSP7-24 ELISA binding levels. These findings strongly suggest that a major autoepitope of native human SS-A/Ro resides on the amino terminal portion of the Wil-2 SS-A/Ro 60 kD polypeptide.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3145881 | Intravenous gammaglobulin in treatment of isoimmune neonatal neutropenia. | 1988 Dec | A neonate with isoimmune neonatal neutropenia (INN) was treated with intravenous gammaglobulin. The neutrophil count increased significantly with the therapy. Intravenous gammaglobulin is a safe and effective regimen for INN. | |
| 3258205 | Anti-idiotypic induced suppression of Sjögren's syndrome associated anti-La autoantibody | 1988 Jan | Peripheral blood mononuclear cells from patients with Sjögren's Syndrome spontaneously secrete autoantibodies to the La antigen when cultured in vitro. This paper reports that specific IgG autoantibody production in vitro is suppressed by pre-treatment of CD8+ enriched T cells with rabbit polyclonal antibodies to idiotypes borne by circulating autologous anti-La antibodies. Treatment of this T cell subpopulation with anti-idiotypes specific for circulating anti-La antibodies from other patients or for anti-DNA antibodies was without effect on anti-La antibody production. Similarly anti-La anti-idiotypes had no effect on the production of autoantibodies to other ribonucleoprotein antigens such as nRNP/Sm. These data show that CD8+ T cells are the main targets for anti-idiotypic control in vitro. We suggest that the relative deficit of these cells, plus a surfeit of CD4+ T cells at the site of the pathological lesion within the salivary gland permits localized production of autoantibodies. Thus, dysregulation of the idiotypic network could contribute to the pathogenesis of Sjögren's Syndrome. | |
| 1834697 | Increased expression of the interleukin 1 receptor on blood neutrophils of humans with the | 1991 Nov | Because of the potential importance of interleukin 1 (IL-1) in modulating inflammation and the observations that human blood neutrophils (PMN) express IL-1 receptors (IL-1R) and synthesize IL-1 alpha and IL-1 beta, we studied the IL-1R on blood PMN from a group of patients with the sepsis syndrome. We report a marked enhancement in the sites per cell of IL-1R expressed on sepsis-PMN of 25 consecutively studied patients compared to 20 controls (patient mean = 9,329 +/- 2,212 SE; control mean = 716 +/- 42 SE, respectively). There was no demonstrable difference in the Kd of IL-1R on sepsis-PMN (approximately 1 nM) as determined by saturation curves of 125I-IL-1 alpha binding and the IL-1R on sepsis-PMN had an apparent Mr approximately 68,000, a value like that of normal PMN. Cytofluorographic analysis indicated that the sepsis-PMN phenotype is a single homogeneous population with respect to IL-1R expression. In contrast, expression of the membrane complement receptor CR3 is not increased on sepsis-PMN. Similar increases in expression of IL-1R were not observed in various other inflammatory processes, including acute disseminated inflammation and organ failure not caused by infection, acute infection without organ failure, and immunopathologies such as active systemic lupus erythematosus and rheumatoid arthritis. Enhanced expression of IL-1R was not related simply to the state of myeloid stimulation. Increased expression of IL-1R on normal PMN was induced in vitro by incubating cells with recombinant human granulocyte-macrophage/colony-stimulating factor for 18 h and this response was inhibited by cycloheximide, suggesting the possibility that de novo synthesis of IL-1R might occur in PMN during the sepsis syndrome. | |
| 2472277 | Expression and regulation of CD5 on in vitro activated human B cells. | 1989 May | The T cell-associated antigen CD5 has been shown to play an important role in the regulation of T cell activation. Monoclonal antibodies directed against CD5 upregulate helper function, and induce interleukin 2 (IL2) production by mature T cells as well as thymocytes. CD5 is also expressed on subsets of B cells associated with autoantibody production, and CD5+ B cells are present in increased numbers in patients with rheumatoid arthritis and systemic lupus erythematosis. More recently CD5 has been found to be present on human B lymphocytes following in vitro activation with phorbol myristate acetate. To date a similar functional role for CD5 has not to date been demonstrated for B cells. In this study we have shown that structurally similar CD5 molecules are present on activated B cells and T cells. In addition, CD5 on both stimulated B cells and T cells is phosphorylated, which may be important in the function of CD5 following activation. CD5 protein or mRNA was not detected on unstimulated splenic B cells depleted of any CD5+ cells. To investigate the control of CD5 expression, we examined a series of cytokines either alone or in combination for their effect on the induction of CD5. CD5 expression was specifically inhibited by IL4 but not by the other cytokines tested. This inhibition was very specific as IL4 did not inhibit the expression of other B cell activation antigens including CD25, B5, T9 and CD23 as well as the pan-B cell antigen CD20. The addition of other cytokines did not increase or reverse the inhibition of CD5 expression by IL4. This inhibition was demonstrated by immunofluorescence and flow cytometric analysis. Immunoprecipitation studies of 125I-labeled activated B cells demonstrated that there was a decrease in cell surface CD5 protein, and not simply inhibition of expression of a particular epitope. Northern blot analysis demonstrated that the expression of CD5 mRNA was markedly inhibited in the presence of IL4, whereas the induction of the protooncogene c-myb was unaffected. This suggests that IL4 inhibits CD5 protein expression on activated B cells by reducing the amount of CD5 mRNA transcription or increasing the degradation of CD5 mRNA. The role of the T cell-derived lymphokine IL4 in regulating CD5 expression may be important in the disease states characterized by increased numbers of CD5+ B cells. | |
| 2928311 | Rat tissues express serum amyloid A protein-related mRNAs. | 1989 Mar | Serum amyloid A (SAA) is a small (12 kDa) acute-phase apoprotein of high density lipoprotein found in mammals. It is also the precursor to amyloid protein A, the main protein constituent of fibrils found in amyloidosis secondary to chronic or recurrent inflammation--e.g., rheumatoid arthritis. However, rats do not develop amyloidosis and SAA is not an apoprotein of rat high density lipoprotein; thus rats appear to be an exception in regard to expression of SAA genes. We report here that rats do have representatives of the SAA gene family and express two distinct SAA mRNAs. Moreover, the pattern of genes expressed among tissues, and their induction by inflammatory agents, is similar to that of related mouse genes. RNA from various tissues of normal and injured rats was examined by RNA blot hybridization with SAA cDNA and complementary RNA probes for the three murine SAA genes. A SAA mRNA of approximately 400 nucleotides related to mouse SAA1 and SAA2 mRNAs reached a high level in liver 24 hr after injection of bacterial lipopolysaccharide. No extra-hepatic tissues were found to express the SAA1/SAA2-related mRNA. Turpentine induced two hepatic SAA1/SAA2-related mRNAs of approximately 400 and approximately 500 nucleotides in length. Liver SAA1/SAA2-related mRNA hybrid selected and translated in a wheat germ protein-synthesizing system, from lipopolysaccharide- and turpentine-injected rats, produced a single protein with an estimated molecular mass of 8 kDa. This rat liver SAA-related mRNA appears to lack a highly conserved coding region for portions of two amphipathic helical domains and the joining sequence. An mRNA related to mouse SAA3 was found expressed at a high level in lung after lipopolysaccharide but not following turpentine injection. This mRNA was also expressed at high levels in ileum and large intestine of control rats and was not found in the liver of control or challenged rats. These observations show that the SAA gene family is present and expressed in rats and that its expression is found under situations similar to those found in mice. This lends support for the importance of the SAA gene family in the response to injury by vertebrates. | |
| 1718800 | CD5+ B lymphocytes in high-risk islet cell antibody-positive and newly diagnosed IDDM subj | 1991 Oct | Human CD5+ B lymphocytes produce autoantibodies that bind to self- and exogenous antigens. Extremely high percentages of CD5+ B lymphocytes are present in the fetal and newborn periods, whereas they constitute only a minority of B lymphocytes in healthy adults. Increased percentages of circulating CD5+ lymphocytes have previously been demonstrated in several autoimmune diseases, including rheumatoid arthritis, progressive systemic sclerosis, Graves' disease, and Sjögren's syndrome. We measured the percentages of B lymphocytes that expressed the CD5 determinant in 93 control subjects (age range 1 day to 59 yr, mean +/- 22.6 +/- 17.7 yr), 17 subjects with newly diagnosed insulin-dependent diabetes mellitus (IDDM; range 5-29 yr, mean +/- SD 13 +/- 5.9 yr), 31 high-risk islet cell antibody (ICA)-positive nondiabetic subjects (range 4-45 yr, mean +/- SD 19.8 +/- 14.1 yr), and 13 subjects with IDDM of greater than 5 yr duration (range 10-43 yr, mean +/- SD 24.2 +/- 9.9 yr). We report that CD5+ B-lymphocyte percentages are strikingly age dependent in healthy control subjects, declining progressively from the newborn period to the middle-age years (r = -0.75, P = 0.0001). In ICA+ nondiabetic and recent-onset IDDM subjects less than 29 yr of age, the percentage of circulating CD5+ B lymphocytes fell within the 95% confidence intervals established for control subjects. However, the age-dependent rate of decline in the percentage of CD5+ B lymphocytes within the control range was slower in ICA+ and newly diagnosed IDDM subjects than in control subjects. | |
| 3496387 | Specificity of monoclonal anti-Z-DNA antibodies from unimmunized MRL/Mp-lpr/lpr mice. | 1987 Aug 1 | Antibodies reactive with left-handed Z-DNA arise spontaneously in the sera of patients with SLE and rheumatoid arthritis and in autoimmune MRL mice. However, the precise specificity of these autoantibodies has not been established. In this report, we have characterized four monoclonal anti-Z-DNA antibodies from unimmunized MRL/Mp-lpr/lpr mice that do not cross-react with B-DNA and can discriminate between different types of left-handed helices. Two of the monoclonal antibodies (Za and Zi) behaved similarly in that they bound to two forms of Z-DNA (Br-poly(dG-dC).poly(dG-dC) and AAF-poly(dG-dC).poly(dG-dC) but not to two other Z-form DNA (poly(dG-5BrdC).poly(dG-5BrdC) or poly(dG-5MedC).poly(dG-5MedC)). Neither antibody (Za or Zi) bound significantly to B-DNA or to denatured DNA. A third antibody (Ze) exhibited similar binding characteristics for the Z-DNA preparations, but also recognized denatured DNA. In contrast, a fourth antibody (3-7.3) bound preferentially to poly(dG-5BrC).poly(dG-5BrdC) in Z conformation. These results provide the first evidence for anti-Z-DNA autoantibodies in autoimmune mice that do not cross-react with native or denatured DNA and indicate that these antibodies exhibit considerable heterogeneity in their fine binding specificity. |