Increased frequency of in vivo hprt gene-mutated T cells in the peripheral blood of patients with systemic sclerosis.

Abstract

Objectives-Activated T lymphocytes are involved in the pathogenesis of scleroderma (systemic sclerosis, SSc); such cells rapidly divide in vivo and are thus theoretically subject to random mutation more frequently than resting cells. To study whether SSc is associated with rapidly expanding T cell clones the frequency was determined of in vivo mutated T cells (MF) at the hypoxanthine guanine phosphoribosyl transferase (hprt) gene in the peripheral blood from patients with SSc.

Assessment of the Frequency of Mutant (hprt-) T Lymphocytes from Peripheral Blood of Patients with Hashimoto's Thyroiditis

“…The observed variance among individual CE estimates under selection or nonselection conditions is also not unusual (13) as it is mainly influenced by the frequency of T cells in the sample. Our results, however, are in contrast to findings for other T-cell-mediated autoimmune diseases such as multiple sclerosis (15,17), type 1 diabetes mellitus (19), rheumatoid arthritis (20), or systemic autoimmune syndromes (17,21,22,24,25), because they do not support a significant difference between the MF values from healthy controls and the patient groups. The reasons for this discrepancy are unclear but the following interpretations are being proposed to …”

“…Under these premises, the mean frequency of mutant (hprt 2 ) T cells in the HT patient population is expected to be higher than the mean frequency of hprt 2 T cells in healthy subjects, because there should be a stronger proliferative response to thyroid antigens, (i.e., more actively dividing T cells) in the first group. This approach has been analogously used to study the frequency, phenotype, or function of peripheral blood mutant T cells in other autoimmune diseases such as multiple sclerosis (15)(16)(17)(18), type 1 diabetes mellitus (19), rheumatoid arthritis (20), systemic lupus erythematosus (21)(22)(23), mixed connective tissue disease (24), and scleroderma (25).…”

HPRT mutations, TCR gene rearrangements, and HTLV‐1 integration sites define in vivo T‐cell clonal lineages

“…Studies have now been reported for multiple sclerosis [Allegretta et al, 1990], Guillain-Barre syndrome [Van den Berg et al, 1995], systemic lupus erythematosus Wood et al, 1994;Theocharis et al, 1995], systemic sclerosis [Sfikakis et al, 1994], mixed connective tissue disease [Holyst et al, 1994], rheumatoid arthritis [Cannons et al, 1998], type 1 diabetes mellitus [Falta et al, 1999[Falta et al, , 2000, paroxysmal nocturnal hemoglobinuria [Chen et al, 2004], and malignant melanoma , with results consistent with the basic hypothesis [Albertini, 2001]. On a practical level, it has been found that sudden and dramatic elevations of HPRT MFs in cardiac transplant recipients have been reliable noninvasive indicators of rejection episodes [Ansari et al, 1995].…”

Nitric oxide donors induce large‐scale deletion mutations in human lymphoblastoid cells: Implications for mutations in T‐lymphocytes from arthritis patients

“…An elevated frequency of hprt mutant T-cells has been found in several autoimmune diseases, including rheumatoid arthritis [Cannons et al, 1998], multiple sclerosis [Sriram, 1994], systemic lupus erythematosus [Dawisha et al, 1994;Theocharis et al, 1995], scleroderma [Sfikakis et al, 1994], juvenile onset dermatomyositis [Abramson et al, 1999], Guillain-Barré syndrome, and chronic inflammatory demyelinating polyneuropathy [Van den Berg et al, 1995]. The cause of this elevated mutant frequency is unknown, although we earlier postulated that genotoxic RNOS at sites of chronic or recurrent inflammation may be responsible [Cannons et al, 1998].…”