Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Those caring for children should recognize that cutaneous findings are common in children with host defense defects. Atopic dermatitis, recurrent or persistent pyodermas, candidiasis and lupus-like syndromes, should signal the possibility of host defense deficiencies. Particularly the findings of atopic dermatitis and recurrent skin abscesses should alert the clinician to determine serum IgE levels and neutrophil chemotaxis in such patients. The triad of generalized seborrheic dermatitis, failure to thrive, and diarrhea in an infant should bring to mind Leiner disease or severe combined immunodeficiency disease.
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PMID:Cutaneous manifestations of defective host defenses. 32 7

Deficiencies of components of the complement system in man are described. Clq was reconstituted in patients with severe combined immunodeficiency after bone marrow transplantation. Clr deficiency is associated with vascular disease and upper respiratory infections. Reconstitution of complement occurred in one patient with Clr deficiency after kidney transplantation. Our C2-deficient patient who developed systemic lupus erythematosus had elevated levels of C3. Following blood transfusion, ie by providing C2, dramatic activation of complement occurred in vivo.
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PMID:Deficiencies of the complement system in man. 80 72

MRL/lpr (lpr) mice spontaneously develop a lupus-like illness as well as massive lymphadenopathy. Attempts to transfer autoimmunity by adoptive transfer or radiation bone marrow chimeras have been unsuccessful. Since severe combined immunodeficiency (SCID) mice have been engrafted with human and rat xenografts without apparent graft-versus-host disease (GVHD), we subjected SCID mice to low-dose irradiation and reconstituted the mice with spleen cells from young or old lpr mice or with lpr bone marrow. Fourteen out of twenty (70%) of SCID mice engrafted with spleen cells from old lpr mice produced autoantibodies (anti-DNA and anti-Sm) without evidence of the severe lymphoid atrophy previously described for lpr spleen-->+/+ chimeras. SCID mice engrafted with spleen cells from young lpr mice developed acute GVHD and 5/6 (83%) died within 4 weeks post-transfer. Although 8/11 (73%) of lpr-->SCID bone marrow allografts survived for at least 4 months, these mice developed a wasting disease characterized by lymphoid atrophy and fibrosis without the production of autoantibodies. None of the lpr-->SCID grafts resulted in the transfer of double negative T cells or the lymphoproliferative syndrome characteristic of MRL/lpr mice. These findings indicate that SCID mice can be engrafted with splenocytes from old MRL/lpr mice and that B cells continue to secrete autoantibodies for several months in the SCID recipients. This study also demonstrates that, unlike i.p. transplant of xenogeneic cells, acute GVHD is a consistent feature of i.p. transplants of normal allogeneic mononuclear cells into SCID mice.
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PMID:MRL/lpr-->severe combined immunodeficiency mouse allografts produce autoantibodies, acute graft-versus-host disease or a wasting syndrome depending on the source of cells. 145 84

Mice with SCID disease have previously been successfully engrafted with human peripheral blood mononuclear cells (PBMC) obtained from normal individuals and from patients with various diseases. To determine whether SCID mice engrafted with SLE PBMC produced autoantibodies with specificities similar to those in the SLE donor, and to investigate which variables influence autoantibody production in the SCID recipients, we injected PBMC from 16 SLE patients into SCID mice and tested the recipients for autoantibodies to DNA and to five recombinant autoantigens. Ten out of 16 (68%) lupus and six out of nine (67%) normal grafts were successful as determined by the presence of human IgG greater than or equal to 5 micrograms/ml of SCID serum post-transfer. Autoantibodies to La/SSB, Ro/SSA, and RNP were detected in five out of 10 SCID-SLE recipients by ELISA and immunoblotting up to 22 weeks post-engraftment. The detection of autoantibodies in SCID-SLE mice was more closely related to autoantibody levels in donor sera than to total IgG concentrations in the SCID recipients. Autoantibody activity/mg IgG was similar in the donor and recipient sera. Histological evaluation of eight SCID-SLE mice killed 4-22 weeks post-transfer revealed population of the SCID thymus and spleen with mononuclear cells, but no evidence of lupus nephritis or dermatitis. These findings indicate that SCID mice can be engrafted with PBMC from patients with lupus and that specific autoantibodies are produced up to 5 months post-transfer. Failure to develop glomerulonephritis may be explained by low or absent anti-DNA antibodies or by changes in the cellular composition of the PBMC grafts.
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PMID:Analysis of autoantibody production in SCID-systemic lupus erythematosus (SLE) chimeras. 156 10

A model in which experimental SLE is induced in normal mice by the injection of a human anti-DNA MoAb expressing a common idiotype 16/6 Id has been established in our laboratory. In the present study we have attempted the induction of experimental SLE in mice with SCID by the transfer of lymphocytes obtained from mice with experimental SLE. Disease could not be induced by direct immunization of SCID mice with the 16/6 Id nor by transfusion of normal splenocytes and immunization with the 16/6 Id thereafter. In contrast, disease was induced in SCID mice which were transplanted with splenic lymphocytes obtained from SLE afflicted BALB/c mice. The disease was expressed by the presence of high titres of antibodies and glomerular immune complex deposits were present in the kidney sections of these mice. Mice that received spleen cells from donors with experimental SLE together with the 16/6 Id developed higher titres of autoantibodies and had, in addition to the immune complex deposits, glomerular histological pathology. The model of experimental SLE induction in SCID mice should help in the elucidation of the role of different cell types in the pathogenesis of SLE.
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PMID:Induction of experimental systemic lupus erythematosus (SLE) in mice with severe combined immunodeficiency (SCID). 163 66

Purine nucleoside phosphorylase (PNP) deficiency is a rare inherited disease accounting for approximately 4% of patients with severe combined immunodeficiency. Thirty-three patients have been reported. PNP-deficient patients suffer from recurrent infections, usually beginning in the first year of life. Two thirds of patients have evidence of neurologic disorders. Findings range from spasticity to developmental delay, to mental retardation. One third of patients develop autoimmune disease. The most common manifestation of this is autoimmune hemolytic anemia. Idiopathic thrombocytopenic purpura and systemic lupus erythematosis have also been reported. Patients usually present with infections but approximately one fourth have come to medical care initially for neurological problems. In PNP deficiency, T- and B-cell immunity are affected. T-cell function may be profoundly deficient, may be normal at birth and then decrease with time, or may fluctuate repeatedly between low and normal. B-cell function can be normal but is deficient in approximately one third of patients. PNP protein is a trimer of approximately 90,000 daltons. It is found in most tissues of the body but is at highest levels in lymphoid tissues. This tissue distribution explains why the lymphoid system is predominantly affected in PNP deficiency. Many mechanisms have been proposed to explain the metabolic toxicity in PNP deficiency. The elevated dGTP found in PNP deficiency is thought to inhibit ribonucleotide reductase and, thus, impede cell division. Depressed GTP levels may correlate with neurologic dysfunction. The gene for PNP has been cloned; it is located on the long arm of chromosome 14. Studies of a mutant PNP gene isolated from one patient showed that a point mutation resulting in an amino acid substitution was responsible for PNP deficiency. PNP deficiency has a grave prognosis. No patient has reached the third decade of life. Twenty-nine of the 33 reported patients have died from their disease. Prenatal diagnosis is currently available. Many different therapies have been utilized for PNP deficiency including bone marrow transplantation, red cell transfusions, and supplementation of the diet with purines and pyrimidines. None of these therapies has been consistently successful. In light of the poor prognosis for PNP deficiency, bone marrow transplantation should be considered for all patients. In the future, improved forms of therapy such as gene therapy may become available.
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PMID:Purine nucleoside phosphorylase deficiency. 193 Oct 7

To study the role of peripheral blood leukocytes (PBL) in the pathogenesis of human systemic lupus erythematosus (SLE), we transferred PBL from 5 SLE patients into 15 severe combined immunodeficiency (SCID) mice. Such reconstituted mice showed long-term presence of auto-antibodies characteristic of the donor in their sera, as well as human immunoglobulin deposition, and in some cases mouse C3, in the renal glomeruli. SCID mice repopulated with PBLs from normal donors do not develop serologic abnormalities or immunodeposits. It is concluded that human SLE serology and some associated renal changes can be reproduced solely by PBL transferred from afflicted patients, and that SCID-human-SLE mice may serve as an in vivo laboratory model for the study of human SLE.
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PMID:Transfer of human systemic lupus erythematosus in severe combined immunodeficient (SCID) mice. 238 39

We investigated the capacity of five human monoclonal IgG anti-DNA antibodies derived from lupus patients to produce glomerular immune deposits. The hybridomas secreting these antibodies were administered intraperitoneally to severe combined immunodeficiency (SCID) mice. Three of the five antibodies (B3, 35.21, 33.C9) were detected in the kidneys, but only one (33.C9) deposited exclusively in the glomeruli in the mesangium and capillary wall, whereas the other two antibodies bound to nuclei both in the kidney and in other organs. The antibodies were tested against a variety of autoantigens by ELISA, the only unique feature of 33.C9 was that it also bound strongly to histones. There were no particular amino acid motif that was related to immunoglobulin deposition in the kidney. All the mice that had immunoglobulin deposited in the kidney, either extracellularly or intranuclearly developed 2 to 3+ proteinuria, whereas the other mice had only trace amounts of proteinuria. This study demonstrates that some human monoclonal IgG anti-dsDNA antibodies are capable of binding to the glomerulus while others can penetrate cells and bind to nuclei in vivo. Although no abnormal pathology was observed, proteinuria was detected, perhaps representing an early phase of disease. These results indicate that the affinity for dsDNA is not the sole determining factor governing the biological properties of human anti-DNA antibodies in vivo.
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PMID:Human IgG anti-DNA antibodies deposit in kidneys and induce proteinuria in SCID mice. 747 55

We have investigated the phenotypic and functional characteristics of murine pre-B cells obtained in semisolid and liquid culture with stem cell factor (SCF) and interleukin 7 (IL-7). Both serum-supplemented and serum-deprived culture conditions were used. The source of bone marrow cells was either normal mice (CD1 and C3H) or the lupus strain of mice MRL/lpr and its congenic strain MRL/+. SCF (100 ng/ml) and IL-7 (250 ng/ml) supported murine B cell proliferation in vitro from all the murine strains analyzed both in serum-supplemented and serum-deprived conditions. Maximal colony growth was observed in both cases when the factors were used in combination. The growth factors alone induced some colony growth in serum-supplemented cultures but were either ineffective or had modest activity in serum-deprived cultures. Cells harvested from the colonies or generated in liquid cultures and stimulated with SCF + IL-7 in the absence of serum had almost exclusively a pre-B cell phenotype (BP-1+, B220+, slg-, CD4-, CD8-, Mac-1-, RB-6-). Both the maximal colony growth in semisolid culture and the maximal number of cells in liquid culture were observed at day 12-14. At this time, the pre-B cells failed to differentiate further and started to die. Pre-B cells generated in vitro were, however, capable of differentiating in vivo. SCID mice injected with 2 x 10(6) pre-B cells had readily detectable serum levels of IgM (54 +/- 26 micrograms/ml) and IgG (60 +/- 95 micrograms/ml) at 4 weeks and 6 weeks posttransplantation, respectively. Mature B and T cells of the donor major histocompatibility complex type were detected in the SCID mice at sacrifice 14 weeks posttransplantation. These data indicate that purified (> 80% BP-1+) populations of functional pre-B cells can be grown from murine bone marrow of normal mice as well as of lupus mice in serum-deprived cultures stimulated with SCF and IL-7. These cultures, therefore, provide a highly enriched source of pre-B cells but also contain T cell precursors that differentiate upon adoptive transfer into SCID mice.
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PMID:Functional characterization of lymphoid cells generated in serum-deprived culture stimulated with stem cell factor and interleukin 7 from normal and autoimmune mice. 754 56

The ability of SCID mice to accept xenografts has been exploited to study the survival, function and potential of peripheral blood mononuclear cells (PBMC) from patients with autoimmune disorders to produce tissue injury in the mouse. Studies performed with PBMC obtained from patients with organ specific and multisystem autoimmune diseases indicate that human PBMC survive in SCID mice for several months, produce IgG and autoantibodies with the same specificities as are found in the donor. Tissue injury is not generally observed in the SCID mouse recipient. SCID mice have also been partially reconstituted with bone marrow from BB (diabetic) and MRL (lupus) mice. SCID mice injected with both spleen cells from mice with collagen induced arthritis together with native bovine collagen developed more severe arthritis than the donors. SCID mice have therefore proven to be a useful resource to study autoimmunity. In both xeno- and allografts of mature lymphocytes, graft versus host reactions occur. Further studies will be necessary to improve donor cell survival without aggravating graft versus host disease.
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PMID:Autoimmunity versus allo- and xeno-reactivity in SCID mice. 780 42


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