Assessment of in vivo frequency of mutated T cells in patients with systemic lupus erythematosus.

Gmelig-Meyling, F.H.J.; Dawisha, Sahar; Steinberg, Alfred D.

doi:10.1084/jem.175.1.297

Cited by 49 publications

(21 citation statements)

References 13 publications

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“…Previous studies of two other autoimmune diseases, mul tiple sclerosis [10] and systemic lupus erythematosus (SLE) [11], have demonstrated that there is an increased frequency of /ip/T-negative cells among patients with these disorders. In chronic multiple sclerosis, Allegretha et al [10] have demonstrated that negative cells can be isolated from these patients.…”

Section: Discussionmentioning

confidence: 99%

“…In SLE, Gmelig-Meyling et al [11] recently demonstrat ed that 14 out of 18 patients had an increased frequency of 236 Holyst/Hill/Sharp/I toffman Mutations in the hprt Gene of T Cells clonable///7/7-negative cells in their peripheral blood. These authors interpreted these results as evidence of in vivo T cell activation among their patients.…”

Section: Discussionmentioning

confidence: 99%

“…T cell activation was not characterized in relation to B cell activation or autoantibody production in the study by Gmelig-Mcyling ct al. [11], how ever. We have recently reported the isolation of snRNP-reactive human T cell clones isolated from SLE and MCTD pa tients [12].…”

Section: Discussionmentioning

confidence: 99%

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Increased Frequency of Mutations in the <i>hprt</i> Gene of T Cells Isolated from Patients with Anti-U1-70kD-Autoantibody-Positive Connective Tissue Disease

Holyst

Hill²,

Sharp³

et al. 1994

Int Arch Allergy Immunol

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Mixed connective tissue disease (MCTD) is characterized by the presence of high titers of anti-U1-70kD autoantibodies which are the result of substantial B cell activation. The hprt gene encodes the constitutively expressed enzyme hypoxanthine-guanine phosphoribosyl transferase which is active in the purine salvage pathway. Rapidly dividing cells randomly accumulate gene mutations, including mutations in the hprt gene. These mutations may be used to identify activated cells. If activated T cells play a role in the pathogenesis of MCTD, an increased frequency of mutations in the hprt gene might be expected among T cells isolated from such patients. To examine this hypothesis, we isolated and cloned T cells from 10 anti-U1-70kD-autoantibody-positive MCTD patients and determined the precursor frequencies of cells possessing mutations in hprt by comparing the frequency of cells grown in the presence and absence of the purine analogue 6-thioguanine. We found that the frequency of 6-thioguanine-resistant hprt-negative T cells was significantly increased among MCTD patients (mean 566/10⁶; range 122–2,845/10⁶) versus age- and sex-matched controls (mean 42/106; range 21–78/10⁶; p < 0.003). These results demonstrate that there is an increase in the measured mutant frequency of T cells from MCTD patients. Such T cells may play a role in the pathogenesis of this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Increased Frequency of Mutations in the <i>hprt</i> Gene of T Cells Isolated from Patients with Anti-U1-70kD-Autoantibody-Positive Connective Tissue Disease

Holyst

Hill²,

Sharp³

et al. 1994

Int Arch Allergy Immunol

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“…Under in vitro conditions T helper cell activity is enhanced, whereas T suppressor cell function is decreased [14]. Furthermore, patients with SLE show a rise in mutated T cells, indicating a disturbance in the immune surveillance [15]. The exaet role ofmonocytes within this altered cellular network in SLE, however, remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Elevated levels of soluble CD 14 in serum of patients with systemic lupus erythematosus

Nockher

Wigand

Schoeppe

et al. 1994

Clinical and Experimental Immunology

105

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SUMMARYA soluble fotin of CD!4 (sCD14) was assessed with an ELISA assay in Ihe serum of the following three clinical groups: 35 patients with ati inactive phase of systemie lupus erylhematosus (SLE). 17 patients with SLE relapses, and 65 normal healthy volunteers, Inereased levels of sCD14 were observed in all patients suffering from SLE compared with normal eontrols. In addition, patients with active SLE revealed higher serum concentrations of sCD14 (median 6-9 mg//) than patients under remission (41 mg//; P<() OO(i\). Serum values of sCDI4 correlated neither with the number of peripheral blood monocytes bearing the CD 14 membrane antigen, nor with serum concentrations of IL-1 p. Serum sCD 14 was compared with other clinical parameters used to monitor the clinical course of patients with SLE, among them complement C3. anti-dsDNA antibodies and soluble IL-2 receptor (sIL-2R). A good correlation emerged between sCD14 and C3 as well as sIL-2R eoneentrations. but sCD 14 and anti-dsDN A titres disclosed no significant correlation in both groups of patients with SLE. Serial studies in patients with severe SLE showed that serum sCD14 closely parallels the clinical course as defined by an activity score. Our data suggest that serum sCD14 represents a promising parameter lo monitor disease activity in patients with SLE.

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“…Studies have shown that any alteration in the balance between clonal deletion and the induction of anergy in autoreactive cells due to impairment of the apoptotic process may lead to the persistence of autoreactive lymphocytes and play a role in the pathogenesis of systemic lupus erythematosus (SLE) [1]. Different oncogenes and cytokines are implicated in the regulation of apoptosis of these Miret/Molina/Filella/García-Carrasco/ Claver/Ingelmo/Ballesta/Font autoreactive cells.…”

Section: Introductionmentioning

confidence: 99%

Relationship of p53 with other Oncogenes, Cytokines and Systemic Lupus Erythematosus Activity

et al. 2003

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Introduction: Defects in the regulation of apoptosis of autoreactive lymphocytes are involved in the pathogenesis of systemic lupus erythematosus (SLE). The apoptotic process relies on adequate functioning of numerous molecules, including oncogenes and diverse cytokines. p53 has been implicated in the control of the cell cycle through the stimulation of apoptosis of these autoreactive cells. Objective: To study the role of the p53 pathway on the regulation of apoptosis in SLE patients and analyze the relationship of the p53 oncoprotein with disease activity and other oncogenes (bcl-2, Fas) and cytokines (interleukin-10, IL-10, and tumor necrosis factor-α, TNF-α), implicated in the apoptotic process and the pathogenesis of SLE. Patients and Methods: p53 and bcl-2 antigen expression were determined in lyzed lymphocytes from 74 patients with SLE and 30 healthy controls. Serum levels of soluble-Fas (sFas) and cytokines IL-10 and TNF-α were studied by enzyme-linked immunonosorbent assay. Results: SLE patients had higher levels of p53 protein (0.16 ± 0.33 ng/dl) than controls (0.014 ± 0.02 ng/dl; p = 0.006). Patients with active SLE had higher levels of p53 (0.31 ± 0.48 ng/dl) than those with inactive disease (0.08 ± 0.17 ng/dl; p = 0.003) who in turn had higher levels than controls (0.01 ± 0.02 ng/dl; p = 0.035). A significant correlation was found between p53 levels and the SLE disease activity index (R = +0.24/ p = 0.04), anti-DNA antibodies (R = +0.23/p = 0.048) and IL-10 levels (R = +0.4/p = 0.004). No correlation was found between p53 levels and bcl-2, sFas or TNF-α levels. Conclusions: The p53 oncoprotein may play a role in the pathogenesis and activity of SLE. IL-10 may influence SLE activity by inhibiting the p53 and bcl-2/Fas apoptosis pathway of autoreactive cells.

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Assessment of in vivo frequency of mutated T cells in patients with systemic lupus erythematosus.

Cited by 49 publications

References 13 publications

Increased Frequency of Mutations in the <i>hprt</i> Gene of T Cells Isolated from Patients with Anti-U1-70kD-Autoantibody-Positive Connective Tissue Disease

Increased Frequency of Mutations in the <i>hprt</i> Gene of T Cells Isolated from Patients with Anti-U1-70kD-Autoantibody-Positive Connective Tissue Disease

Elevated levels of soluble CD 14 in serum of patients with systemic lupus erythematosus

Relationship of p53 with other Oncogenes, Cytokines and Systemic Lupus Erythematosus Activity

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