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)

To investigate the capacity of lupus autoAb to produce glomerular immune deposits (ID) and nephritis, 24 murine monoclonal (m) anti-DNA antibodies (Ab), derived from either MRL-lpr/lpr, SNF1 or NZB lupus-prone mice and selected based on properties shared with nephritogenic Ig, were administered i.p. (as hybridomas) and i.v. (as purified Ig) to normal mice; at least four mice/mAb were evaluated. Three general patterns of immune deposit formation (IDF) were observed: extracellular ID within glomeruli (+/- blood vessels, N = 8); intranuclear ID (N = 5); or minimal or no ID (N = 11). The four MRL m anti-DNA Ab that produced significant extracellular ID demonstrated different disease profiles including: (a) mesangial and subendothelial ID with anti-basement membrane staining, associated with proliferative glomerulonephritis, PMN infiltration, and proteinuria; (b) diffuse fine granular mesangial and extraglomerular vascular ID, associated with proliferative glomerulonephritis and proteinuria; (c) dense intramembranous ID and intraluminal ID, associated with capillary wall thickening, mesangial interposition and expansion, aneurysmal dilatation and intraluminal occlusion of glomerular capillary loops, and heavy proteinuria; and (d) mesangial and extraglomerular vascular ID, associated with mild segmental mesangial expansion, without proteinuria. These MRL mAb were derived from four different mice, and they had variable pIs and isotypes. They all cross reacted with multiple autoantigens (autoAg), however, their autoAg binding profiles were distinguishable. Among the SNF1 derived mAb, four produced histologically and clinically indistinguishable disease characterized by diffuse mesangial and capillary wall ID, associated with cellular proliferation/infiltration and proteinuria. Three of the four mAb were derived from the same mouse and were clonally related; they were: IgG2b with SWR allotype, relatively cationic, highly cross reactive with similar Ag binding patterns, idiotypically related and encoded by identical VH and nearly identical VL sequences. We conclude that both the capacity of lupus autoAb to form ID and the location of IDF are dependent on properties unique to individual Ig. The results also indicate that the Ag binding region of the autoAb is influential in this process, and they suggest that multiple Ab-Ag interactions contribute to IDF in individuals with lupus nephritis. Furthermore, these observations raise the possibility that the pathologic and clinical abnormalities resulting from these interactions are influenced by the location of IDF, and that the dominant interaction, in a given individual, may be highly influential in the phenotypic expression of nephritis.
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PMID:Anti-DNA antibodies form immune deposits at distinct glomerular and vascular sites. 150 24

The peripolar cell is a recently described glomerular epithelial cell which is situated within Bowman's capsule at the vascular pole. It contains cytoplasmic granules which contain plasma proteins, although it may also have a secretory function. The relationship between peripolar cells, other granulated glomerular epithelial cells and tubular epithelial cells is unclear. We have studied 242 biopsies from 19 types of renal disease for peripolar cells, other granulated epithelial cells and granulated tubular epithelial cells. Peripolar cells were most numerous in mesangioproliferative glomerulonephritis, IgA nephropathy, focal segmental glomerulosclerosis, membranous glomerulonephritis and lupus nephropathy. Other granulated glomerular epithelial cells were most prominent in diffuse lupus nephropathy, focal glomerulonephritis, acute vascular transplant rejection, crescentic glomerulonephritis and mesangioproliferative glomerulonephritis. Granulation of the tubular epithelium was most prominent in minimal change nephrotic syndrome and amyloidosis. It is likely that the granules in tubular epithelial cells represent lysosomes containing plasma proteins which have been absorbed from the tubular fluid. However, granulation of glomerular cells may represent a more specific response to glomerular damage. In addition, peripolar cells are prominent in only certain diseases, suggesting a specialized function.
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PMID:Peripolar cells and other granulated epithelial cells in renal biopsies. 152 Apr 82

The accelerated development of lupus-like autoimmune disease in male BXSB mice (H-2b, I-E-) is associated to the presence of a mutant gene, designated Yaa, located on their Y chromosome. To investigate whether the H-2b haplotype and/or the lack of expression of I-E molecules play any role in the Yaa-linked acceleration of autoimmune disease, an I-E+ BXSB.H-2d congenic strain was created by backcross procedures. We compared the development of autoimmune disease in the novel BXSB.H-2d (I-E+) strain to that of BXSB.H-2b (I-E-) and BXSB.H-2b/d (I-E+) heterozygous mice. Male BXSB.H-2d (I-E+) mice exhibited only a limited production of autoantibodies and a lower incidence of glomerulonephritis with a markedly prolonged survival rate, which were essentially identical to those of female BXSB mice of both-H-2b and H-2d haplotypes. However, BXSB.H-2b/d (I-E+) heterozygous males developed an accelerated disease comparable to that of conventional BXSB.H-2b (I-E-) male mice. These results indicate that the expression of I-E molecules and consequent clonal deletion or anergy of I-E reactive T cells does not appear to be responsible for the prevention of accelerated autoimmune disease in BXSB.H-2d (I-E+) male mice. The finding that the Yaa gene-induced acceleration of lupus-like autoimmune disease is modulated by gene(s) within or closely linked to the H-2 complex underlines the crucial role of the major histocompatibility complex and the polygenetic nature of autoimmune disease in BXSB mice.
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PMID:H-2-linked control of the Yaa gene-induced acceleration of lupus-like autoimmune disease in BXSB mice. 153 72

BALB/c mice injected at birth with 10(8) semi-allogeneic (C57BL/6 x BALB.IgHb)F1 spleen cells develop a lupus-like syndrome in which autoantibodies bear exclusively the donor allotype. We have analyzed the evolution of donor B cell chimerism and the autoimmune manifestations during the first year of life in these mice. Anti-DNA, -histone, and -cardiolipin IgG antibodies as well as circulating immune complexes appeared in the second week of life, reached the highest values around the sixth week, and then progressively dropped to normal values after the sixth month in most mice. The kinetics of the evolution of the autoimmune manifestations, as well as the kinetics of serum donor Ig allotype, were parallel to the kinetics of donor B cell chimerism, which was particularly prominent in the spleens in early weeks of life, and progressively decreased after remission of the autoimmune syndrome. Membrane-proliferative glomerulonephritis, which was followed as the more representative histological abnormality in this model, was particularly evident after 10 weeks of life, but disappeared by the end of the follow-up. Interestingly, when mice with a self-limited disease were re-injected with 10(8) F1 spleen cells i.v., a flare in the serological manifestations was observed. In these re-injected mice a predominance of anti-DNA, IgG1 antibodies bearing exclusively the donor allotype was also observed, as in the early weeks of life.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Self-limited autoimmune disease related to transient donor B cell activation in mice neonatally injected with semi-allogeneic F1 cells. 154 May 50

A 51-year-old woman had been suffering from blood-stained purulent sinusitis and antibiotic-resistant bouts of fever for 4 months. She had microhematuria and serological evidence of inflammation (erythrocyte sedimentation rate [ESR] 92/135 mm, C-reactive protein 5.0 mg/dl). When she was admitted to hospital suspected of having postinfectious glomerulonephritis she complained of spontaneous colic-like pains in the left flank. Within one day the haemoglobin concentration fell from 10 to 6.5 g/dl. Ultrasound and computed tomography demonstrated a large space-occupying lesion around the left kidney. At operation this was found to be a rupture of the kidney with perirenal bleeding which was treated without removing the kidney. No biopsy was taken, but serological tests showed antineutrophil cytoplasmatic antibodies (cANCA), indicating Wegener's granulomatosis as the cause of the compensated renal insufficiency and spontaneous renal rupture. Under immunosuppressive treatment the inflammatory signs (ESR 18/44 mm), fever, chronic maxillary sinusitis, raised serum creatinine concentration and the ANCA titre all regressed, while proteinuria of about 4 g/24 h persisted. There was no recurrence during a follow-up period of 15 months. Serological signs of marked inflammatory activity, urinary sediments of nephritis and spontaneous retroperitoneal bleeding should suggest that, in addition to lupus erythematodes and panarteritis nodosa, Wegener's granulomatosis be included in the differential diagnosis.
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PMID:[Spontaneous kidney rupture as an early complication of Wegener's granulomatosis]. 154 1

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 17-year old-male presented with a 6-week history of weight loss, lassitude and calf pains. On examination he was very pale. Laboratory tests showed a very high erythrocyte sedimentation rate (155 mm in the first hour), anaemia (haemoglobin 10.1 g/dl), and a raised serum creatinine of 1.54 mg/dl. Microhaematuria (5-10 erythrocytes/microliter) and pronounced pyuria (500 leucocytes/microliter) were present, but the urine was sterile and there was no increase in albumin excretion. The serum IgG was raised to 75.7 g/l, suggesting an autoimmune disorder. Anti-nuclear antibodies (titre 1 : 1920) and anti-double-stranded DNA antibodies (31 U/ml) were present, while the serum complement C4 was decreased to 0.11 g/l. Renal histology showed an interstitial nephritis without glomerular involvement, while the bone marrow showed vasculitis accompanied by a prominent plasma-cell infiltrate. A diagnosis of interstitial nephritis associated with systemic lupus erythematosus was made, with asymptomatic cardiac and hepatic involvement. Renal function recovered rapidly with prednisolone therapy (initial dose 2 mg/kg.d). While glomerulonephritis is the most common lupus-associated renal disorder, isolated interstitial nephritis may occur in some cases, often with an absence of proteinuria.
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PMID:[Interstitial lupus nephritis]. 158 9

Graves' disease was initially diagnosed in an 11-year-old Chinese boy in March 1989. After regular propylthiouracil (PTU) and thyroxine, he achieved a euthyroid state. Heavy proteinuria with class IV lupus glomerulonephritis, anemia, arthralgia, low serum complement and anti-dsDNA (+) appeared 15 months later. Thyrotoxicosis also relapsed at this time. His condition fitted the diagnostic criteria of systemic lupus erythematosus. His antimicrosomal antibody titer was 1:1,600 (+) thyroid-stimulating hormone receptor antibody level was strongly positive, and the titer of antiinsulin antibody was high as well. These clinical, laboratory and histological findings indicate that class IV lupus nephritis may be associated with Graves' disease.
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PMID:Class IV lupus nephritis associated with Graves' disease. 160 84

Renal lesions at the chronic phase of MHC class-II-disparate graft-versus-host reaction (GVHR) were examined. To induce GVHR, C57BL/6 (B6) spleen cells were injected twice into either (B6 x bm12)F1 (class-II-disparate), (B6 x bm1)F1 (class-I-disparate) or (bm1 x bm12)F1 mice (class-I + II-disparate). For comparison, (C57BL/10 x DBA/2)F1 (BDF1) mice injected with DBA/2 spleen cells were also used. (B6 x bm12)F1 and BDF1 recipients showed marked elevation of anti-DNA antibodies, circulating immune complexes (CIC) and the number of immunoglobulin producing cells (IgPC). At 20 weeks after cell injection, severe immune complex glomerulonephritis (ICGN) was observed in (B6 x bm12)F1 recipients, but was far less severe in (bm1 x bm12)F1 recipients and was not observed in (B6 x bm1)F1 recipients. ICGN was also observed in BDF1 recipients at 12 weeks after cell injection. By immunofluorescent microscopy, IC deposition was detected along the capillary loops and also in the mesangial area in (B6 x bm12)F1 recipients, while BDF1 recipients showed only a capillary pattern. By light microscopy, the renal lesion of (B6 x bm12)F1 recipients appeared similar to those of BDF1 recipients. Histologically, (B6 x bm12)F1 recipients serve as a good model for lupus glomerulonephritis induced by class-II-disparate GVHR.
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PMID:Histological characteristics of lupus nephritis in F1 mice with chronic graft-versus-host reaction across MHC class II difference. 161 13

64 pregnancies were analyzed in 41 women with biopsy-proven lupus nephritis between 1965-91; fetal and maternal outcome were evaluated and risk factors for poor outcome were identified. Of 65 fetuses, 22 (34%) were lost (including therapeutic abortions). 19 (30%) were liveborn but premature (or= 36 weeks gestation) and 24 (37%) were term. Fetal loss after 20 weeks gestation was 195. 12% of 25 fetuses whose birthweight was recorded were small for gestational age. Maternal renal function deteriorated in 19% of the pregnancies but was irreversible postpartum in only 1 woman (2%). Hypertension was recorded in 44% of pregnancies, developed early (or= 32 weeks gestation) in 28%, and was severe in 13%. Treated hypertension predated 17% of the pregnancies and in 6% (included in the overall incidence of hypertension) exacerbation occurred during pregnancy despite continued antihypertensive medication. 9 women (22%) who developed de novo hypertension in pregnancy had permanent hypertension postpartum. Increased proteinuria was recorded in 485 of pregnancies and was irreversible postpartum in 5%. The comparison of pregnancies occurring before or after diagnosis was made by renal biopsy and failed to show any significant difference in fetal outcome. Pregnancies which occurred after the diagnosis of glomerulonephritis were associated with a significantly lower incidence of maternal hypertension, early hypertension, severe hypertension, and increased proteinuria. The presence of circulating lupus anticoagulant was clearly associated with a significantly higher fetal loss rate although the incidence of maternal complications did not differ significantly between mothers positive or negative for lupus anticoagulant.
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PMID:Lupus nephritis and pregnancy. 163 Dec 63


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