Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The local response of 18 patients with active systemic lupus erythematosus to 0.1 ml of intradermally injected 0.1% polymerized calf thymus DNA and synthetic double-stranded polyinosinic-polycytidylic acid was studied. In 14 patients positive for DNA, 61 +/- 8% of the inflammatory cells in the subepidermis at 24 hours were acid alpha-naphthyl acetate esterase-positive T lymphocytes. A leukocytoclastic vasculitis was observed in the deeper dermis. Rheumatoid arthritis patients and acne patients had negative responses. These results indicated an abnormal cellular and humoral in vivo response by patients with systemic lupus to DNA. It is suggested that the epidermal Langerhans cells were responsible for the topographic dichotomy of the local DNA response. Test results were positive for polyinosinic-polycytidylic acid in 12 patients, for DNA in 14 patients, and for both in 9 patients. In the 9 patients with positive results for both tests, comparison of responses to each test indicated that the reaction intensity was dependent on the patient and not on the type of polynucleotide acid that was injected.
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PMID:Skin response to intradermal DNA and RNA in systemic lupus erythematosus. 618 90

The Sm antigen was isolated and purified from calf thymus nuclear extract by affinity chromatography. The affinity columns were made with serum antibodies from an SLE patient or an anti-Sm monoclonal antibody derived from a hybridoma cell line. Proteins eluted from these two columns had m.w. of 58,000 and 35,000 by SDS polyacrylamide gel electrophoresis. The natural conformation of this antigen appears to be 95,000 in m.w. with the 58,000 particle containing the Sm antigenic determinant. The affinity column-purified antigen detected by the human anti-Sm antibodies is also recognized by anti-Sm antibodies in murine lupus serum, as shown by solid-phase radioimmunoassay. This study 1) demonstrates the molecular and antigenic nature of the Sm antigen and 2) compares the anti-Sm binding capabilities of antibody populations present in sera from SLE patients and from MRL lpr/lpr mice.
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PMID:Molecular and antigenic nature of isolated Sm. 618

This paper reports three cases of lupus erythematosus (LE) associated with thymomas, all of which were discovered after the onset of LE. The diagnosis of LE was established by clinical and laboratory data. Histologically, the thymomas were of the three main types: epithelial, lympho-epithelial, and predominantly fusiform. In two cases, thymectomy did not modify the course of LE; in one vase, the absence of cytoplasmic secretory vesicles in the epithelial cells and the non-labelling of these cells by an antiserum thymic factor monoclonal antibody represented direct evidence of a functional thymus deficiency. Antikeratin antibodies were used to distinguish thymomas from lymphomas; epithelial thymomas exhibited the same keratin specificities as normal thymus, although the labelling pattern (net-like) was different. Labelling of epidermis with the same antiserum confirmed the theory of an epidermis-thymus relationship.
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PMID:Thymoma and lupus erythematosus. Report of 3 cases. 619 60

A common cellular abnormality of all murine strains prone to systemic lupus erythematosus (SLE) is an increased spontaneous polyclonal expansion of B cells. Our findings support the existence of this SLE-associated abnormality because the numbers of B lymphocytes secreting all the different IgG subclasses and IgM in spleens of all lupus-prone mice are elevated, compared to levels of normal splenic immunoglobulin-producing cells. We also report that 1) spontaneous polyclonal stimulation of immunoglobulin in autoimmune mice is preferential for subclass, and that the preferentially stimulated isotypes in each SLE strain consistently dominate both circulating and kidney-deposited immune complexes; 2) distinct patterns of isotype preference exist among the autoimmune strains determined by inherent B cell proliferative abnormalities or by B cell proliferation affected by thymus-derived lymphocytes; and 3) chronic administration of the TI B cell mitogen Lipid A in late-life SLE-prone mice induces an early-life glomerulonephritis with auto-antibodies of an isotype composition characteristic of those spontaneously produced by inherently abnormal B cells of early-life lupus mice.
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PMID:Isotypes of spontaneous and mitogen-induced autoantibodies in SLE-prone mice. 653 61

Nude mice (strains ORL, C57BL, BALB/C), as well as neonatally thymectomized mice, develop spontaneous antinuclear antibodies (ANab) and antidouble-stranded DNA antibodies (dsDNAab). Later, these animals develop a lupus-like syndrome in which immunoglobulin (Ig) deposits appear, first in the kidney glomeruli, then at the dermoepidermal junction and in the choroid plexus. In the beginning, these Ig are IgM and IgG2; later, IgG1 and IgA deposit in the kidneys. The classes of the Ig of the deposits correspond to those of the circulating ANab-Ig, except for IgA. Acid eluates from kidneys and skin, contain anti-DNA histone ab. An increased C1q binding activity is observed in 8- to 12-wk-old ORL nude mice with ANab, but is not observed in age-matched ORL nude mice without ANab. These data indicate the participation of ANab in the constitution of immune complexes and of tissular Ig deposits in nude mice. The antinuclear autoimmunization process, in nude as well as in thymectomized mice, might be interpreted as a defect of T suppressor cells, which normally control autoimmune clones. However, in contrast with the preceding strains of nude mice, nude mice from the IFFA centre, which have a different genetic background, develop neither ANab, nor dsDNAab, nor glomerular lesions. Three hypotheses can be proposed to explain these particularities of IFFA nude mice. They either have an immune response regulating system, independent of the thymus which is defective or absent in the other strains, or they are deprived of lymphocytes able to produce ANab and dsDNAab, or there are not enough free nuclear antigens to stimulate an immune response. Preliminary results obtained in our laboratory favour the first hypothesis.
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PMID:Lupus-like syndrome in some strains of nude mice. 696 75

Evidence has been obtained previously indicating that the antigens reacting with the anti-Sm and anti-RNP sera are present as a large complex, and similar protein bands are obtained with both types of sera. Inthe present study, it proved possible to break up this complex using SDS treatment before immunoprecipitation. After such treatment, different protein bands were immunoprecipitated by the two antisera; Sm determinants resided, at least partially, in a 19-kd protein. Sequential immunoprecipitation with and without prior SDS treatment provided further evidence for these specificities and suggested that two classes of particles exist in different tissues, one containing proteins immunoreactive with the Sn and RNP antisera and the other containing proteins immunoreactive only with the Sm antisera. The latter particle contained all the bands seen with the first type except for the absence of the 19-kd band. Nitrocellulose blot analyses confirmed the assignment of the 25- and 16-kd polypeptides to Sm antigenic determinants; analyses for RNP proved les informative by this technique. Some differences in the banding patterns were obtained using cells from different species: the 25-kd Sm band was usually double in human cells and single in rat and rabbit tissue. Methods of extraction also caused some differences which was especially true for the rabbit thymus extract widely used for Sm and RNP studies. Additional immunoreactive bands at 68 and 70 kd also were detected when the Sm and RNP antisera were used in nitrocellulose blot analyses. Furthermore, evidence was obtained for a number of other antibodies in lupus sera which have not as yet been detected by serological methods.
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PMID:Protein antigens of the RNA-protein complexes detected by anti-SM and anti-RNP antibodies found in serum of patients with systemic lupus erythematosus and related disorders. 713 Sep 4

To elucidate the interaction of anti-DNA antibodies with DNA, the reactivity of lupus sera with single-stranded fragments from calf thymus, Escherichia coli, and salmon testes DNA was investigated. These fragments were generated by digestion with the restriction enzyme HinfI and ranged in size from approximately 100-4000 bases. By ELISA using polystyrene microtiter plates, fragments from all three species were weakly antigenic compared to intact DNA. These fragments, however, were all antigenic when tested as inhibitors in competition-binding assays. The weak antigenicity of fragments could not be explained by poor adherence to the plates since fragments and intact DNA showed similar levels of binding as assessed using biotinylated preparations. Together, these results demonstrate that the antigenicity of DNA fragments is dramatically altered by solid-phase binding and suggest that constraints on topological or conformational rearrangements of DNA in the solid phase limit antibody interaction.
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PMID:The influence of DNA size on the binding of anti-DNA antibodies in the solid and fluid phase. 752 Mar 75

Long-term administration of low doses (5 micrograms) of recombinant nucleobindin (rNuc), which is an MRL/lpr/lpr (MRL/l) mouse-derived DNA-binding protein, induces autoimmunity in both young lupus-prone MRL/+/+ (MRL/n) and normal BALB/c mice. In relation to this autoimmunity, using agarose gel electrophoresis we found an approximately 160 bp mono-nucleosomal DNA (nsDNA) in the sera of 6-week-old normal mice 15 h after i.p. injection of 50 micrograms rNuc. Co-injection of rNuc (50 micrograms) and anti-CD3 monoclonal antibody (mAb, 50 micrograms) further accelerated the appearance of nsDNA in the serum together with DNA fragmentation (apoptosis) in the thymus, which had not been so clearly induced by either double amounts of rNuc or anti-CD3 mAb alone. Acceleration of the appearance of nsDNA in the serum by co-injection was also found in age-matched MRL/n and MRL/l mice, indicating the close association of apoptosis in the thymus with the appearance of nsDNA in the serum. Furthermore, we have detected naturally occurring tri-, di- and mono-nsDNAs from immune complexes (IC) of the sera of 20 approximately 22-week-old MRL/l mice, which indicates that apoptosis in the lymphoid tissues, including the thymus, is the source of serum nsDNA that may trigger or continue production of anti-nuclear antibodies. Evidence that clearance of nsDNA from the circulation is retarded in the presence of rNuc in BALB/c mice may give rationale to the induction of autoimmunity in normal mice by long-term administration of even low doses (5 micrograms) of rNuc after all.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction and natural occurrence of serum nucleosomal DNA in autoimmune MRL/lpr/lpr mice: its relation to apoptosis in the thymus. 759 Sep 21

To define age-associated alterations in the immune system at the molecular level, we have analyzed TCR V beta gene expression patterns at the fetal, neonatal, adult, and advanced ages of mice. In contrast to V gamma and VH genes, V beta genes rearranged without any preference related to their chromosomal organization. Endogenous superantigen-mediated clonal deletions were registered for the first time at the neonatal stage, presumably reflecting the late developmental appearance of these molecules. Such deletions, once established, were maintained throughout life with little, if any, leakage in this process. Furthermore, bone marrow transplantation and other studies indicated that an involuted thymus maintained its capacity to perform both its functions, i.e. positive and negative selection. Although overall V beta repertoires showed remarkable stability with advanced age, modifications in expression levels for some V beta, particularly those associated with the CD8 subset and presumably reflecting antigenic stimulation, were recorded. Mice with lupus and early-life thymic involution were fully capable of deleting endogenous superantigen-reactive V beta clones, and even lupus mice with a genetic defect in the apoptosis-promoting Fas gene were normal in this regard. The results indicate that, aside from some anticipated clonal expansions induced by antigenic stimulation, age-associated alterations in immune functions are not caused by any profound changes in the overall TCR repertoire.
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PMID:V beta gene repertoire in the aging mouse: a developmental perspective. 759 12

The lymphoproliferation (lpr) mutation in the MRL strain of mice is caused by the insertion of the early transposable element ETn in the Fas gene. The insertion causes a striking decrease in Fas mRNA expression and is associated clinically with marked acceleration of the lupus-like disease. To further explore the role of the Fas protein in T-cell selection in the thymus and tolerance in the peripheral immune system, we produced a monospecific polyclonal anti-murine Fas antibody that binds to a polymorphic region of the protein. Fas protein expression was detected on approximately 90% of BALB/c and MRL +/+ thymocytes, and the expression was highest on CD4+CD8+ thymocytes, the stage at which most thymocytes die by apoptosis. In contrast to the high level of expression of Fas on thymocytes, Fas was detected on < 10% of normal splenic T cells. After activation of splenic T cells with Con A or anti-CD3 and interleukin 2, Fas expression increased approximately 10-fold. Fas expression on splenic B cells was also markedly up-regulated after activation with lipopolysaccharide or anti-mu antibodies. The Fas protein was not detected on resting or activated lymphocytes obtained from MRL lpr/lpr mice. Together, these findings suggest that Fas plays a role in both thymic selection and T-cell survival in the periphery and that the accelerated autoimmunity in MRL lpr/lpr mice results from a defect in both of these pathways.
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PMID:The Fas protein is expressed at high levels on CD4+CD8+ thymocytes and activated mature lymphocytes in normal mice but not in the lupus-prone strain, MRL lpr/lpr. 769 92


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