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

The presence and distribution of Ia antigen in normal human kidneys and biopsy specimens from patients with renal disease were investigated by immunohistochemical techniques using two monoclonal antibodies to the nonpolymorphic determinants of human HLA-DR molecules. Ia antigen was found on the endothelium of glomerular and peritubular capillaries and of veins and vasa recta. Loss of endothelial staining was found in necrotic and sclerotic glomerular and tubulointerstitial lesions. Staining or decreased staining was also not found in the severe proliferative nephritis of systemic lupus erythematosus although endothelial cells could still be identified upon light microscopic examination of the same biopsy specimen. Resting and proliferating cells in mesangial areas did not stain with anti-Ia antibody and extracapillary proliferating cells did not express Ia antigen except for occasional cells in anti-GBM crescentic glomerulonephritis, suggesting that Ia-bearing cells are not involved in mesangial and most extracapillary proliferations in human glomerulonephritis. All clustered mononuclear cells infiltrating the renal interstitium stained with anti-Ia antibody regardless of the type of nephritis where infiltrates occurred.
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PMID:Immunohistochemical study of Ia antigen in the normal and diseased human kidney. 620 99

Recurrence of the original disease in the transplanted kidney is observed in 5.6%-9.3% of the patients. However, the clinical significance of recurrence is often minor. Diagnosis is easy in diseases with specific renal lesions, e.g., in dense deposit disease and IgA-nephropathy, but may be difficult if such a marker is missing. Recurrence is of special clinical importance in the following conditions: Membranoproliferative GN type I (in 33%, often severe) and type II (= dense deposit disease, recurrence in 90%, often minor), focal segmental glomerulosclerosis (in 48% of patients with a rapid course (less than 3 years) and in 12% of patients with a longer duration of the original disease; often severe), membranous nephropathy (recurrence rather rare, but often serious), and primary hyperoxaluria (in 100%). Mesangial IgA deposits recur in half of the patients with IgA-nephropathy and anaphylactoid purpura, but clinical findings are often minimal. Recurrence in anti-GBM-nephritis and SLE is rare. The study of recurrence may contribute to a better understanding of many renal diseases.
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PMID:[Recurrence of the original disease in the transplanted kidney]. 637 74

In order to elucidate their role in mediating renal immune injury in man, the glomerular C3b receptors have been analyzed in frozen sections of 205 kidneys biopsied from 199 patients affected by various well-defined renal diseases. Using fluoresceinated C3b-coated bacteria as the indicator system, the receptor activity has been compared with that found in 10 normal human kidneys. In 76 out of 98 cases (77%) of glomerulonephritis (GN) with capillary wall abnormalities, a significant loss of receptor activity has been observed. No difference was present between the 89 patients affected by GN presumably due to immune complexes (ICX) parietal deposition (membranoproliferative, membranous, acute poststreptococcal GN and proliferative GN of SLE and cryoglobulinemia) and the 9 patients affected by GN presumably due to anti-GBM antibodies (Goodpasture's syndrome and extracapillary GN). In the group of ICX-GN, no correlation could be demonstrated between inhibition of C3b receptors and the presence of parietal C3 deposits. A significant loss of receptors activity has been also demonstrated in 12 out of 13 patients with amyloidosis or diabetic glomerulosclerosis. On the contrary, inhibition of C3b receptors has been observed in only 3 out of 20 patients with nonglomerular renal diseases (interstitial and vascular nephropathies) and in only 11 out of 57 patients (19%) affected by mesangial GN with no capillary wall abnormalities (Berger's disease, Henoch-Schonlein purpura and mesangial GN of SLE). C3b receptors were normal in 13 out of 17 patients affected by lipoid nephrosis (minimal change GN or focal glomerulosclerosis). In conclusion, the analysis of C3b receptors in renal diseases do not support the hypothesis of their involvement in parietal localization of C3b-bearing ICX: these results rather suggest that the receptors become undetectable in many glomerular diseases (immune-mediated or not) with lesions of capillary walls, because of the loss of integrity of C3b receptor-bearing visceral epithelial cells.
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PMID:Significance of glomerular C3b receptors in human renal diseases. 645 26

A critical discussion of data on the possible role of IgG3 cryoglobulins, cross-reactive anti-DNA antibodies and anti-DNA idiotypes in the pathogenesis of lupus nephritis is included. A further possibility involving cationic nuclear autoantigens is presented in detail. Histone was employed as a model antigen, representative of this group. Histones were shown to have high affinity for the rat GBM; they could also act as planted antigen and induce IC formation; furthermore they were able to mediate the binding of highly anionic DNA. The demonstration of histones in glomerular deposits in both lupus mice and patients with SLE is important evidence, linking such molecules with the kidney lesions.
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PMID:Nephritogenic antibodies in lupus nephritis. 780 10

A 58-year-old woman was admitted with cough, dyspnea on effort and diffuse micronodular and patchy shadows on her chest roentgenograms. Two weeks later, acute pulmonary hemorrhage developed with low levels of complement and positive immune complexes. She was diagnosed as having systemic lupus erythematosus (SLE) with positive anti-nuclear antibody, positive anti-DNA antibody, biologically false positive Wassermann reaction, auto-immune hemolytic anemia and photosensitive dermatoses. In addition, anti-glomerular basement membrane antibody (anti-GBM antibody) was positive in serum, but pulmonary hemorrhage was thought to be secondary to SLE, since the renal biopsy showed lupus nephritis. Cases of SLE with positive anti-GBM antibody are seldom confirmed. It was assumed that the basement membrane of the lung or kidney was damaged first by interstitial pneumonitis due to SLE or lupus nephritis, basement membranes antigens were exposed, with secondary production of anti-GBM antibody.
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PMID:[A case of acute pulmonary hemorrhage and positive anti-glomerular basement membrane antibody in systemic lupus erythematosus]. 851 7

In this study of antineutrophil cytoplasmic antibody (ANCA)-associated diseases, we determined the prevalence of other autoantibodies and the antigen specificities of ANCA. ANA were common, occurring in 7 of 36 (19%) patients with Wegener's granulomatosis, in 16 of 34 (47%) patients with microscopic polyarteritis, in 6 of 11 (55%) patients with segmental necrotising glomerulonephritis and in 8 of 18 (44%) of those with ANCA-associated systemic vasculitis without renal involvement. ANA were associated more often with pANCA and microscopic polyarteritis than with cANCA (P < 0.05). Patterns were speckled (n = 23), homogeneous (n = 10) or nucleolar (n = 4). Anticardiolipin antibodies were also common, occurring in 10 of 25 (40%) patients with Wegener's granulomatosis, in 8 of 14 (57%) patients with microscopic polyarteritis and in 6 of 18 (33%) of those with a systemic vasculitis. However, anticardiolipin antibodies did not correlate with the presence of ANCA in any of the disease groups. Anti-GBM antibodies were demonstrated in only 2 of 25 (8%) patients with Wegener's granulomatosis, in 1 patient with microscopic polyarteritis (1/14, 7%) and in 1 with segmental necrotising glomerulonephritis (1/11, 9%). All four patients with anti-GBM antibodies had either cANCA or pANCA. In the second part of the study, the target antigens of ANCA were determined in Wegener's granulomatosis, microscopic polyarteritis, systemic vasculitis, inflammatory bowel disease, rheumatoid arthritis and systemic lupus erythematosus (SLE). Of the 19 sera with cANCA, 13 (68%) were directed against proteinase 3; other antigens were myeloperoxidase (1/19, 5%), elastase and lactoferrin together (1/19, 5%), lysozyme (1/19, 5%) or unknown (3/19, 16%). Of the 12 (58%) sera from patients with Wegener's granulomatosis who had cANCA, 7 bound to proteinase 3. Antimyeloperoxidase antibodies were present in 14 of 45 (31%) sera with pANCA; other antigens were proteinase 3 (5/45, 11%), elastase (3/45, 78%), lactoferrin (1/45, 2%), cathepsin G (5/45, 11%) or unknown (17/45, 38%). Antimyeloperoxidase antibodies were common in microscopic polyarteritis (6/14, 43%) and systemic vasculitis (5/16, 31%). However, the majority of target antigens in systemic vasculitis and rheumatoid arthritis with pANCA were not determined. "Atypical" ANCA were present in four patients, one with inflammatory bowel disease (1/8, 13%) and three with SLE (3/15, 20%). The specificities were cathepsin G, cathepsin G plus lactoferrin, or unknown in two sera. A recent report has suggested that bactericidal/permeability-increasing protein may be the target in patients with inflammatory bowel disease.
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PMID:Autoantibodies and target antigens in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. 889 75

Susceptibility to systemic lupus erythematosus (SLE) and, in particular, lupus nephritis is strongly influenced by genetic factors. Previous studies have shown that MHC-related antigens influence the development of SLE. In the current study, we set out to investigate how non-MHC genes influence the pathogenesis of glomerulonephritis in chronic graft-versus-host disease (GVHD) in mice, a model for lupus nephritis. For the induction of GVHD we used parent-to-F1 hybrid mouse strain combinations. DBA/2, BALB/c, BALB.D2 and C57B1/10.D2 (BL10.D2) donor lymphocytes carrying an H-2d haplotype were injected into H-2b/d F1 hybrids of BL10 mice, which differed only at non-MHC loci. Within these hybrid strains the development of immune complex glomerulonephritis was investigated by monitoring the occurrence of autoantibodies in the circulation, deposition of immunoglobulins in the glomeruli, development of albuminuria, and glomerulosclerosis. In diseased DBA/2 mice albuminuria developed 6 weeks after induction of the disease. Mice with a BALB background developed a lupus-like syndrome characterized by albuminuria starting 8 weeks after induction of the GVHD. During the development of the GVHD, polyclonal B cell activation occurred in both the DBA/2 and BALB/c strains, resulting in the formation of autoantibodies. Only the strain combination using DBA/2 mice developed anti-GBM antibodies. In DBA/2 and BALB strain combinations immune complexes were detected in a granular pattern along the glomerular capillary walls. In the DBA/2 recipients a linear pattern of immunoglobulin depositions preceded the granular phase. This study demonstrates that: (i) non-MHC genes govern the pathogenesis of immune complex nephritis in this model by influencing the autoantibody profile; and (ii) the presence of anti-GBM antibodies in the early stages of the disease is a conditio sine qua non for the development of full-blown glomerulonephritis and glomerulosclerosis in this model.
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PMID:Non-MHC genes determine the development of lupus nephritis in H-2 identical mouse strains. 891 72

It is generally assumed that anti-dsDNA antibodies play an important role in the pathogenesis of lupus nephritis. This is mainly based on the facts that an increase in anti-dsDNA titer often precedes onset of renal disease, that immune deposits are present in glomeruli and that eluates of glomeruli are enriched for anti-dsDNA. This led to the classical concept that deposition of DNA-anti-DNA complexes incites the glomerular inflammation. However, important pieces of evidence are lacking to support this hypothesis. Free, naked, DNA is not present in the circulation. The existence of DNA/anti-DNA complexes is highly questionable and injection of these complexes hardly leads to glomerular localization. As an alternative concept cross-reactivity of anti-dsDNA with glomerular constituents like heparan sulfate (HS) and laminin has been proposed. However, subsequent research has indicated that this cross-reactivity is due to nucleosomal antigens (histones and DNA) complexed to the auto-antibodies. The cationic histone part of the complex is responsible for the binding to the anionic HS. This binding also occurs in vivo since renal perfusion of nucleosome complexed antibodies leads to abundant binding of auto-antibodies to the GBM, while enzymatic removal of HS from the GBM, decreases this binding considerably. Non-complexed antibodies did not bind at all. This mechanism of binding is also consistent with the decrease of HS staining in the GBM in human and murine lupus due to masking of HS with nucleosome-complexed auto-antibodies. Furthermore the presence of histones and nucleosomes in glomerular deposits in lupus nephritis was recently shown. Elution of auto-antibodies from glomeruli not only showed anti-dsDNA but also anti-nucleosome specificities. Nucleosomes are not only important for the induction of glomerular lesions, but there is now also increasing evidence that the nucleosome is the auto-antigen that drives the auto-immune response in SLE. There is ample evidence that this response is antigen-driven and T cell dependent. However immunization with DNA in general fails to induce pathogenic anti-dsDNA antibodies. Recently, in SLE T helper cells were identified specific for nucleosomes. These nucleosome specific T helper cells were not only able to induce anti-nucleosome antibodies but also anti-dsDNA and anti-histone antibodies. This is in line with the finding that in SLE nucleosome specific antibodies are formed. These antibodies react exclusively with nucleosomes and not with its constituents DNA or histones. The formation of these nucleosome specific antibodies precedes the development of anti-dsDNA or anti-histone suggesting that the loss of tolerance for nucleosomes is a primary event. The systemic release of nucleosomes is due to an aberrant apoptosis. There is now growing evidence that apoptosis is disturbed both in certain murine lupus models as well as in human lupus. In conclusion, nucleosomes seem to play a central role in the induction and the effector phase of SLE.
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PMID:Autoimmunity against nucleosomes and lupus nephritis. 909 59

Histopathology and direct immunofluorescence (DIF) microscopy were performed on renal biopsy specimens of 60 clinically suspected cases of glomerulonephritis (GN). Histopathological diagnosis was obtained in 44 (73.3%) cases and immune complex deposition were detected by DIF in 28 (46.7%) cases. Immune complex deposition were observed in all cases of membranous GN, systemic lupus erythematosus (SLE), and rapidly progressive GN (RPGN), most of the cases of diffuse proliferative GN (2 out of 3) mesangioproliferative GN (12 out of 15) and focal glomeruloscleros is (3 out of 5 cases). No immune deposits were observed in minimal change GN, chronic GN, and diabetic nephropathy. Histopathological diagnosis was not obtained in 16 (26.7%) cases, 3 (5%) of which showed immune complex deposition by DIF. Anti-GBM nephritis was demonstrated in one (3.6%) case, the rest were immune complex nephritis.
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PMID:Immunofluorescent microscopic findings in glomerulonephritis. 962 76

Recurrent or de novo glomerular disease is an important cause of graft dysfunction and eventual loss. Cyclosporine A (CyA) has improved short-term renal allograft outcome but has not altered long-term graft survival. The purpose of the current study is to determine the prevalence of such disease and its impact on graft function in the CyA era. From 1984 to 1994, 1,557 renal allografts were performed at the Medical College of Wisconsin and the University of Cincinnati. Patients were followed up for an average of 7.2 years (minimum, 1 year). Recurrent disease was diagnosed by renal biopsy in 98 (6.3%) patients after an average of 36 months. Demographic characteristics of patients with and without recurrent disease were similar. Glomerulonephritis was the most common finding, occurring in 73 patients, and included focal segmental glomerulosclerosis (FSGS), 25; IgA nephropathy (IgAN), 11; membranous (MN), 11; proliferative, 11; membranoproliferative glomerulonephritis (MPGN), 10; glomerular basement membrane (anti-GBM), 3; and systemic lupus erythematosus (SLE), two. Diabetic nephropathy was present in 22, hemolytic uremic syndrome (HUS) in two, and oxalosis in one. Graft loss occurred in 60 of 98 (61%) recipients. Half-life of the allograft was diminished in patients with recurrent disease, 2,038 +/- 225 versus 3,135 +/- 385 days, P = 0.002. The actuarial allograft survival at 1, 3, 5, and 8 years posttransplantation with recurrence was 88%, 74%, 57%, and 34%, respectively; and the corresponding graft survival for patients without recurrent disease was 80%, 70%, 64%, and 53%, respectively (P = 0.003). The risk of recurrent disease increased with length of graft survival from 2.8% at 2 years to 9.8% and 18.5% at 5 and 8 years, respectively. We conclude that recurrent disease is a significant problem after renal transplantation and is associated with decreased graft survival.
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PMID:Recurrent and de novo renal diseases after renal transplantation: a report from the renal allograft disease registry. 963 35


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