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 acute-phase plasma protein response to disease activity in murine models of autoimmune lupus-like disease was investigated by measurement of the concentration of serum amyloid P component (SAP) in NZB X W and MRL/l mice. The levels of SAP, which is a major acute-phase protein in mice, did not rise at all in response to progression of disease in NZB X W mice between the ages of 1 and 9 mo. This resembles the behavior of acute-phase proteins such as C-reactive protein and serum amyloid A protein in human systemic lupus erythematosus, and just as in human lupus, where the occurrence of intercurrent microbial infection can stimulate an acute-phase response, so injection of bacterial lipopolysaccharide or casein into the NZB X W mice stimulated "normal" acute-phase SAP production. In marked contrast, MRL/l mice developed greatly increased levels of SAP, which correlated closely with progression of their pathology as they aged. The disease profile of the MRL/l strain includes rheumatoid factors and spontaneous polyarthritis and their SAP response resembles the behavior of acute phase proteins in human rheumatoid arthritis. Different patterns of acute-phase response in different autoimmune disorders may thus be a reflection of the genetic predisposition to particular diseases and/or contribute to their pathogenesis. The existence of animal counterparts for the various clinical patterns of human acute-phase protein production will assist in experimental investigation of the underlying mechanisms and of the biological role of the acute-phase response.
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PMID:The acute-phase response in (NZB X NZW)F1 and MRL/l MICE. 715 12

Pentraxins are a family of pentameric serum proteins that have been conserved in evolution and share sequence homology, similar subunit assembly and the capacity for calcium-dependent ligand binding. The classical pentraxins are human C-reactive protein (CRP) and serum amyloid P component (SAP). The sequence homology and gene organization indicate that they arose from a gene duplication of an ancestral pentraxin gene. They are usually isolated based on their affinity for phosphorylcholine and agarose, respectively. We have used this method for isolation of pentraxin-like proteins from normal serum of Atlantic salmon (Salmo salar), common wolffish (Anarhichas lupus), cod (Gadus morhua) and halibut (Hippoglossus hippoglossus). Although pentraxin structures have not been verified, the isolated proteins all appear to be pentraxin-like based on their binding specificity, molecular weight of subunits, cross-reactivity with antibodies to human pentraxins and N-terminal amino acid sequences. However, with the described method only one pentraxin-like protein was detected in each of the fish species.
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PMID:A comparative study of pentraxin-like proteins in different fish species. 963 88

Genetic studies in mice indicate that predisposition to lupus-like diseases is caused by at least three mechanisms: (1) alterations in the threshold of activation of lymphocytes or macrophages; (2) defective signaling for activation-induced cell death; and (3) reduced clearance of apoptotic cells. To define the mechanisms whereby lupus develops in mice with deficiencies in either C1q, serum amyloid P component (SAP, the mouse counterpart of C-reactive protein, or CRP), or serum IgM, we studied the efficiency of phagocytosis of apoptotic cells using serum with varying levels of C1q, CRP, or IgM; we also examined the immune response to ingestion of dying cells under these conditions. Deficiency of C1q led to impaired macrophage phagocytosis of apoptotic cells, whereas CRP augmented phagocytosis, largely through recruitment of the early complement components. Like CRP, normal polyclonal IgM bound to apoptotic cells and activated complement on the cell surface. Similarly, direct binding as well as absorption experiments revealed that CRP and IgM antibodies had a similar ligand recognition specificity, namely lysophospholipids containing phosphorylcholine. IL-12 provides a pivotal link between macrophages and the T cell response to ingested material. We observed that necrotic cells induced IL-12 p40 expression, whereas phagocytosis of apoptotic cells profoundly reduced IL-12 production from stimulated macrophages. Furthermore, soluble factors from macrophages that had ingested apoptotic cells suppressed interferon-gamma production by activated T cells. These findings suggest that phospholipid exposure on apoptotic cells promotes opsonization by serum proteins leading to activation of complement, macrophage ingestion, and T cell suppression. We discuss how deficient opsonization or processing of dying cells leads to autoimmunity.
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PMID:Opsonization of apoptotic cells and its effect on macrophage and T cell immune responses. 1272 25

Relative deficiency of pentraxin proteins is implicated in the pathogenesis of systemic lupus erythematosus. The C-reactive protein (CRP) response is defective in patients with acute flares of disease, and mice with targeted deletions of the serum amyloid P component gene (Sap) develop a lupus-like illness. In humans, the genes for CRP (CRP) and SAP (APCS) map to 1q23.2 within an interval linked with SLE. We have investigated the candidate genes CRP and APCS in two cohorts totalling 586 UK simplex SLE families. The inheritance of an intronic dinucleotide repeat and seven single nucleotide polymorphisms in the CRP and APCS genes was examined by application of family-based tests of association and linkage. Basal levels of CRP were influenced independently by two polymorphisms at the CRP locus, CRP 2 and CRP 4. Furthermore, the latter polymorphism was linked/associated with SLE and antinuclear autoantibody production. Thus, the polymorphism associated with reduced basal CRP was also associated with the development of SLE. These data support the hypothesis that defective disposal of potentially immunogenic material is a contributory factor in lupus pathogenesis. The identification of polymorphisms that determine basal CRP levels has implications in ischaemic heart disease, where CRP level is an important predictor of risk.
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PMID:Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus. 1464 6