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)

The basal and stimulated intracellular cyclic AMP (cAMP) levels of peripheral blood mononuclear cells (PBMC) of 16 control subjects and 14 patients with systemic lupus erythematosus (SLE), all fulfilling the ARA criteria, were studied. No significant difference in basal cAMP level was observed between SLE patients and controls. SLE lymphocytes (both active and inactive) elicited a diminished response to aminophylline and prostaglandin E2 (PGE2). No correlation was seen between disease activity and either baseline cAMP levels or response to these stimulators. We suggest an intrinsic (not disease activity-related) impairment of the adenylate cyclase-dependent regulatory mechanism in the PBMC of SLE patients, which may result in a defective IL-2 production and IL-2 dependent biological functions.
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PMID:Cyclic AMP level of lymphocytes in patients with systemic lupus erythematosus and its relation to disease activity. 255 72

Normal human T lymphocytes incubated with adenosine (10 muM) for 30 min at 37 degrees C show an increase in the percentage of cells expressing receptors for the Fc portion of IgG (RFc(gamma)) and the OKT8 antigen, while the proportion of OKT4(+) cells decreases. These effects occur exclusively in a subset of T cells with theophylline-resistant sheep erythrocyte receptors (T(R) cells) that is enriched for OKT4(+) cells. Untreated normal T(R) cells express helper/inducer cell activity for T-cell-dependent B-cell differentiation, while adenosine-treated T(R) cells suppress B-cell differentiation. In contrast, in T(R) cells isolated from patients with systemic lupus erythematosus (SLE), adenosine fails to induce immunosuppressor activity or to increase the percentage of OKT8(+) and RFc(gamma) (+) cells. In addition, although incubation of normal T(R) cells with adenosine causes a transient increase in cAMP levels (up to 160% of control within 5 min), in SLE T(R) cells, cAMP levels fall by 50% within 10 min. The photoaffinity label 8-azidoadenosine cyclic [(32)P]monophosphate has been used to show that human T lymphocytes have a single cAMP receptor site that appears to be the regulatory subunit of type I protein kinase. In normal T(R) cells, this receptor becomes occupied in response to adenosine. In contrast, in SLE T(R) cells, no change in cAMP receptor occupancy is detected. Although adenosine has a differential effect on normal and SLE T(R) cells, cAMP derivatives that can traverse the cell membrane (8-bromo- and 8-azidoadenosine cyclic monophosphates) induce an increase in the RFc(gamma) (+) cell subset in both normal and SLE T(R) cells. These results suggest that cAMP mediates the effects of adenosine on cell surface markers of T lymphocytes. The lack of an adenosine receptor-coupled adenylate cyclase activity in SLE T(R) cells may account, in part, for their lack of immunosuppressive activity.
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PMID:Abnormal adenosine-induced immunosuppression and cAMP metabolism in T lymphocytes of patients with systemic lupus erythematosus. 629 38

Systemic lupus erythematosus (SLE) is an autoimmune disorder of indeterminate etiology characterized by a dysfunctional cellular immune response. We have previously identified a metabolic disorder of the adenylate cyclase/cAMP/protein kinase A (AC/cAMP/PKA) pathway characterized by impaired cAMP-inducible, PKA-catalyzed protein phosphorylation in intact T lymphocytes from subjects with severe SLE disease activity. Because this metabolic disorder may contribute to abnormal T cell immune effector functions, we tested the hypothesis that impaired PKA-dependent protein phosphorylation is the result of a PKA isozyme deficiency in SLE T lymphocytes. Compared with healthy and rheumatoid arthritis (RA) controls, subjects with severe SLE activity exhibited reduced PKA-catalyzed phosphorylation of proteins in the T lymphocyte plasma membrane where the type I isozyme of PKA (PKA-I) is predominantly localized. Both silver staining and biosynthetic labeling of membrane-associated proteins with [35S]methionine demonstrated that reduced protein phosphorylation was not due to either an altered distribution of or absence of proteins. Moreover, phosphorylation of SLE membrane-associated proteins with the PKA catalytic (C) subunit showed a similar distribution and extent of phosphorylation compared with membrane proteins from healthy T cells, suggesting that SLE T cell membrane proteins could be phosphorylated. Sequential column chromatography of the type I and type II isozymes of PKA (PKA-I, PKA-II) demonstrated a deficiency of PKA-I isozyme activity. Compared with a ratio of PKA-I to PKA-II activity of 4.2:1 in healthy T cells, the activity ratio in T cells from subjects with severe SLE disease activity was 0.99:1 (P = 0.01, SLE versus healthy controls for PKA-I). The deficient PKA-I activity was associated with a significant increase of free C-subunit activity (P = 0.04, SLE versus healthy controls for C-subunit). T cells from subjects with mild/moderate SLE disease activity also exhibited diminished PKA-I activity, yielding a ratio of PKA-I to PKA-II activity of 2.4:1. By contrast, T cells from RA controls possessed increased PKA-I, PKA-II, and free C-subunit activities compared with healthy controls, resulting in a ratio of PKA-I to PKA-II activity of 3.6:1. We conclude that the reduced PKA-catalyzed protein phosphorylation in the plasma membrane of SLE T cells is the result of deficient PKA-I isozyme activity. This is the first identification of a deficiency of PKA activity in SLE T lymphocytes; the deficiency, resulting in diminished protein phosphorylation, may alter cellular homeostasis, contributing to the cellular immune dysfunctions observed in SLE.
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PMID:Deficient type I protein kinase A isozyme activity in systemic lupus erythematosus T lymphocytes. 804 Feb 83