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)

Fifty-five patients with systemic lupus erythematosus (SLE) were examined for antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IIF). Enzyme-linked immunosorbent assay (ELISA) for ANCA against myeloperoxidase (MPO), lactoferrin (LF), proteinase 3 (PR3), elastase (HLE), and bactericidal/permeability-increasing protein (BPI) was performed. The prevalence of ANCA by IIF was 29.1% (16/55 patients). MPO-ANCA were found in 10.9% (6/55), LF-ANCA in 18.2% (10/55), PR3-ANCA in 12.7% (7/55), BPI-ANCA in 23.6% (13/55), and HLE-ANCA in 1.8% (1/55). The levels of BPI-, LF-, and PR3-ANCA correlated with disease activity. A significant association between serositis and the presence of BPI-, LF-, and PR3-ANCA was observed, and PR3-ANCA were found to be associated with arthritis as well. Our results demonstrate that ANCA of various specificities occur in SLE, and BPI appears to be an important target antigen.
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PMID:Antineutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus: prevalence, antigen specificity, and clinical associations. 1151 40

Various autoantibodies like anti-nuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), anti-histone antibodies (AHA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-myeloperoxidase (anti-MPO), anti-proteinase3 (anti-PR3) and anti-lactoferrin (anti-LF) antibodies were studied in 173 acute hospitalised patients suffering from malaria of which 160 patients had P. falciparum and remaining 13 had P. vivax infection. Standard methods like indirect immunofluorescence (IIF) microscopy along with Confocal microscopy and ELISA were used for identifying and quantifying the autoantibodies and IIF patterns on PMN and HL-60 cells were studied for ANCA classification. Also HEp-2 cells were used for ANA detection, while estimation of anti-dsDNA, AHA, anti-MPO, anti-PR3 and anti-LF were tested using ELISA. Sera from malaria patients showed prominent immunofluorescence staining patterns where 23.8% cases had ANA in P. falciparum group as compared to 15.4% in P. vivax group and ANCA was found to be present in 20% in P. falciparum and 15.4% in P. vivax group. An interesting observation was that, of the total ANCA positives, 59% had p-ANCA, 5.9% had c-ANCA and 44.1% of the cases showed the 'atypical' or X-ANCA pattern. When p-ANCA positivity was compared with c-ANCA positivity among these patients, a good statistical correlation was noted with OR = 16, chi 2 = 16.43, EF = 0.46 and p-value = 5.037E 0.5. ELISA showed 31.2% anti-MPO and 6.2% anti-PR3 in P. falciparum cases while the two ANCA positive cases in P. vivax had anti-MPO. Anti-LF was found to be present in 40.6% cases. Neither the P. falciparum nor P. vivax contained autoantibodies with specificities similar to the characteristic lupus autoantibodies such as double stranded DNA (dsDNA). ANCA positivity develops in some types of malarial infection also with the presence of various autoantibodies which is important from a clinical point of view and should be carefully evaluated in those geographic areas where malaria is endemic. It also alerts us to the fact, whether in cases of repeated malarial infections in susceptible individuals, vasculitic disorders, which through ANCA pathways develop, could lead to renal and other complications.
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PMID:Anti-neutrophil cytoplasmic antibodies (ANCA) in malaria. 1468 12

Lactoferrin (LF) is a multifunctional iron-binding protein present in several mucosal secretions as well as in secondary granules of polymorphonuclear leukocytes (PMN). Anti-LF antibodies, which belong to antineutrophil cytoplasmic antibodies (ANCA), have been described in several immunomediated diseases, including systemic lupus erythematosus (SLE), with conflicting results regarding either their prevalence or clinical associations. We studied the prevalence and isotype distribution of anti-LF and their association with clinical manifestations, disease activity, and other autoantibodies in 97 patients (83 women) affected by SLE. Anti-LF were detected by enzyme-linked immunosorbent assay. Disease activity was assessed using the Systemic Lupus Activity Measure (SLAM). Cutoff for antibody positivity was set at three standard deviations (SD) above the mean optical density obtained in sera from 34 healthy subjects. Positive sera were arbitrarily subdivided into low (from >3 to 5 SD), medium (from >5 to 10 SD), and high (>10 SD) positive. IgG, IgM, and IgA anti-LF were detected in 53, 18, and 14 patients, respectively. IgG1, IgG2, IgG3, and IgG4 anti-LF were demonstrated in 34, 10, 31, and 35 patients, respectively. IgG anti-LF at the medium/high level were found in 33 patients, correlated with disease activity (p = 0.017), anti-dsDNA (0.04), and anticardiolipin antibodies (p = 0.02) and were associated with Raynaud's phenomenon (p = 0.028), renal involvement (p = 0.007), serositis (p = 0.026), and history of thrombosis (p = 0.006). Anti-LF of IgM, IgA, or IgG subclass isotypes showed no correlation with clinical and serological findings. Our results demonstrate that anti-LF are frequently present in patients affected by SLE. IgG anti-LF at the medium/high level are associated with some clinical manifestations and other autoantibodies. However, it remains to be established whether anti-LF play a specific pathogenic role.
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PMID:Anti-lactoferrin antibodies in systemic lupus erythematosus: isotypes and clinical correlates. 1559 2

It is conceivable that a membrane component(s) is transferred from antigen-presenting cells to T cells after antigenic stimulation. However, it is not clear whether a certain membrane component(s) is transferred from polymorphonuclear neturophils (PMN) to T cells for immunomodulation. In the presence study, we cocultured two of the three autologous cells-PMN, CD4+ T, and red blood cells (RBC)-homotypically or heterotypically for 1 h. Spontaneous membrane exchange between autologous PMN-PMN and PMN-CD4+ T but not between CD4+ T-CD4+ T or RBC-CD4+ T was observed with a confocal microscope. Loss of membrane exchange between two paraformaldehyde-fixed cells suggests that mutual membrane exchange is via cell-cell contact. Different combinations of cellular enzyme-linked immunosorbent assay for measuring the binding between fixed cells and biotinylated cell lysates showed the same tendency. To identify the molecule(s) mediating PMN-CD4+ T binding, we compared the banding of biotinylated PMN lysates and the banding of plain PMN lysate probed by biotinylated CD4+ T lysate in 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We found that a 75- to 80-kDa surface-expressed molecule on PMN exists constantly to mediate PMN-CD4+ T binding. Peptide analysis disclosed that the molecule had 99.8% identity with lactoferrin (LF). The expression of LF on system lupus erythematosis (SLE)-PMN is less than normal PMN. PMN-CD4+ T coculture increased LF expression on CD4+ T. Normal PMN and human milk-derived LF suppressed interferon-gamma (IFN-gamma) but enhanced interleukin (IL)-10 production of anti-CD3+anti-CD28-activated, normal CD4+ T. In contrast, coculture of SLE-PMN and autologous CD4+ T suppressed IFN-gamma and IL-10 production. These results suggest that the surface-expressed LF released from PMN after contact with autologous CD4+ T modulated its T helper cell type 1 (Th1)/Th2 cytokine production. Decreased LF expression on SLE-PMN abnormally modulates Th1/Th2 production by CD4+ T cells.
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PMID:Release of surface-expressed lactoferrin from polymorphonuclear neutrophils after contact with CD4+ T cells and its modulation on Th1/Th2 cytokine production. 1676 65

Levels of lactoferrin (LF), antithrombin-III (AT-III) and beta2-macroglobulin (MG) in blood of patients with rheumatoid arthritis (RA), reactive arthritis (ReA) and systemic lupus erythematosus (SLE) were examined for assessment their importance in differential diagnostics of the diseases. It was shown that on the average, LF and AT-III levels were increased at RA, while MG level was practically unchanged. At the same time LF level was stable high regardless of RA activity and duration degree, but its concentration was significantly increased also in ReA patients (33% patients). AT-III, on the contrary, depended on process activity and duration, was more specific to RA, than LF, but its sensitivity at RA was not enough high (from 25 to 44% patients with increased levels subject to disease duration and activity). Coefficient LFE/AT-III, obtained by multiplication of these proteins concentration, had the greatest diagnostic value. Its sensitivity at RA is on the average 85%, and specificity at differential diagnostics of RA--80% vs. ReA and 92% vs. SLE. We consider that coefficient LFbetaAT-III can be used as an additional criterion at differential diagnostics at RA early stages, while other specific antibodies cannot be detected yet.
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PMID:[Some proteins of acute phase of inflammation in differential diagnostics of rheumatoid arthritis]. 1872 Jul 14


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