Association of Erythrodermic Cutaneous T-Cell Lymphoma, Superantigen-Positive Staphylococcus aureus, and Oligoclonal T-Cell Receptor Vβ Gene Expansion

Forty-two patients with cutaneous T-cell lymphoma, including 31 with exfoliative erythroderma or Sezary syndrome and 11 with mycosis fungoides, were studied for the occurrence of staphylococcal infection. Thirty-two of 42 (76%) had a positive staphylococcal culture from skin or blood. One half of the patients with positive cultures grew Staphylococcus aureus. This group included 11 with Sezary syndrome and 5 with rapidly enlarging mycosis fungoides plaques or tumors. All of the S aureus carried enterotoxin genes. Surprisingly, 6 of 16 strains were the same toxic shock toxin-1 (TSST-1)-positive clone, designated electrophoretic type (ET)-41. Analysis of the T-cell receptor Vβ repertoire in 14 CTCL patients found that only 4 had the expected monoclonal expansion of a specific Vβ gene, whereas 10 had oligoclonal or polyclonal expansion of several Vβ families. All patients with TSST-1+S aureus had overexpansion of Vβ 2 in blood and/or skin lesions. These studies show that S aureus containing superantigen enterotoxins are commonly found in patients with CTCL, especially individuals with erythroderma where they could exacerbate and/or perpetuate stimulate chronic T-cell expansion and cutaneous inflammation. Attention to toxigenic S aureus in CTCL patients would be expected to improve the quality of care and outcome of this patient population.

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Association of Erythrodermic Cutaneous T-Cell Lymphoma, Superantigen-Positive Staphylococcus aureus, and Oligoclonal T-Cell Receptor Vβ Gene Expansion

Blood ◽

10.1182/blood.v89.1.32 ◽

1997 ◽

Vol 89 (1) ◽

pp. 32-40 ◽

Cited By ~ 172

Author(s):

Clotilde M. Jackow ◽

Jennifer C. Cather ◽

Vicki Hearne ◽

Arisa T. Asano ◽

James M. Musser ◽

...

Keyword(s):

Staphylococcus Aureus ◽

T Cell ◽

Mycosis Fungoides ◽

T Cell Receptor ◽

Cell Lymphoma ◽

Cell Receptor ◽

T Cell Lymphoma ◽

Sézary Syndrome ◽

Cutaneous T Cell Lymphoma ◽

T Cell Receptor Vβ

Abstract Forty-two patients with cutaneous T-cell lymphoma, including 31 with exfoliative erythroderma or Sezary syndrome and 11 with mycosis fungoides, were studied for the occurrence of staphylococcal infection. Thirty-two of 42 (76%) had a positive staphylococcal culture from skin or blood. One half of the patients with positive cultures grew Staphylococcus aureus. This group included 11 with Sezary syndrome and 5 with rapidly enlarging mycosis fungoides plaques or tumors. All of the S aureus carried enterotoxin genes. Surprisingly, 6 of 16 strains were the same toxic shock toxin-1 (TSST-1)-positive clone, designated electrophoretic type (ET)-41. Analysis of the T-cell receptor Vβ repertoire in 14 CTCL patients found that only 4 had the expected monoclonal expansion of a specific Vβ gene, whereas 10 had oligoclonal or polyclonal expansion of several Vβ families. All patients with TSST-1+S aureus had overexpansion of Vβ 2 in blood and/or skin lesions. These studies show that S aureus containing superantigen enterotoxins are commonly found in patients with CTCL, especially individuals with erythroderma where they could exacerbate and/or perpetuate stimulate chronic T-cell expansion and cutaneous inflammation. Attention to toxigenic S aureus in CTCL patients would be expected to improve the quality of care and outcome of this patient population.

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The Expression of T Cell Receptor Signaling Genes Is Associated with Poor Response to IFN-α and/or PUVA in Mycosis Fungoides.

Blood ◽

10.1182/blood.v108.11.2053.2053 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2053-2053

Author(s):

Magdalena Wozniak ◽

Pablo Ortiz ◽

Lorraine Tracey ◽

Jose L. Peralto ◽

Monica Alvarez ◽

...

Keyword(s):

T Cell ◽

Signaling Pathway ◽

Mycosis Fungoides ◽

T Cell Receptor ◽

Cell Lymphoma ◽

Cell Receptor ◽

T Cell Lymphoma ◽

Cutaneous T Cell Lymphoma ◽

T Cell Receptor Signaling ◽

Cell Receptor Signaling

Abstract Mycosis fungoides (MF) is a low-grade cutaneous T-cell lymphoma, in which malignant T cell clones (mostly CD4+) arise in the skin from the early disease stages. IFN-α is widely used in the treatment of MF and when used in combination with PUVA has been reported as an effective treatment, with overall response rates of 30%–80%, and complete response rates of 14%–25%. However, up to date there is no information available on prognostic factors that could help to predict response to IFN-α /PUVA in MF. The purpose of the study was to find the molecular signature associated with IFN-α /PUVA resistance, or lack of remission after IFN-α /PUVA treatment. The gene expression profile of the pre-treatment samples from 30 MF patients enrolled in a random clinical trial with IFN-α and/or PUVA has been analyzed by use of cDNA microarrays. Following the treatment outcome, the patients have been divided into good responders (23 patients that have achieved complete remission in the time of 24 weeks or less) and bad responders (7 patients that have not reached completed remission or have shown progression of the disease during treatment). The genes associated with good vs. bad response have been identified. Four genes associated with cell cycle regulation and tumour microenviroment have been identified to predict good response by the significance analysis of microarrays (SAM) correlating expression data with survival time. Moreover, 38 genes involved in T cell receptor signaling pathway, NF-kB activation and Jak-Stat signaling pathway have been found to be associated with unfavorable response to treatment by use of SAM analysis. This was validated using other bioinformatics tools based on t-statistics and Cox-model, applying False Discovery Rate for multiple testing. Furthermore, using a web-based tool (Signs) that uses a combination of gene filtering, clustering and survival model building, a 2-gene model has been obtained. This model could distinguish two groups of MF patients with probability of remission at 24 weeks of 15%, and 60% (log-rank test, p:0.007). This confirms that TCR-signaling plays a key role in cutaneous T-cell lymphoma cell survival; and could potentially be used for stratifying MF patients treated with IFN-α /PUVA into different risk-groups, if confirmed in additional studies.

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