Sézary syndrome(SS) is an aggressive variant of cutaneous T cell lymphoma characterized by the presence of malignant T cells in the skin, peripheral blood and lymph nodes. The tumoral population typically display...Sézary syndrome(SS) is an aggressive variant of cutaneous T cell lymphoma characterized by the presence of malignant T cells in the skin, peripheral blood and lymph nodes. The tumoral population typically displays a CD3+ CD4+ CD45RO+ memory T cell phenotype. We report a case of SS with an aberrant CD56+ immunophenotype. This patient presented with a generalized erythroderma and palpable small axillary lymph nodes.SS(stage IVA) was diagnosed on histological criteria and by the detection of a major T cell clone in skin and blood, an elevated CD4/CD8 T cell ratio and Sézary cells count > 1000/mm3. Beside the Sézary cell marker KIR3DL2, immunostainings revealed that two third of the malignant cells expressed CD56 but no other natural killer(NK) cell marker such as CD16, CD160 or NKp46. This atypical expression was not linked to an activation-dependent process and remained stable during the time course of the disease. No loss of the panT-cell markers CD2, CD3 or CD4 was detected while a complete down-modulation of CD26 was observed. Despite several lines of treatment, no durable amelioration was observed and patient died after 10 mo of follow-up. Because this CD4+ CD56+ SS case is the only one reported so far, the functional significance of CD56 expression remained difficult to assess in terms of aggressiveness and prognosis.展开更多
Mycosis fungoides is the most common form of cutaneous T-cell lymphoma(CTCL), and is characterized by a clonal expansion of malignant CD4+ T lymphocytes with skinhoming properties. Clinically and pathologically, mycos...Mycosis fungoides is the most common form of cutaneous T-cell lymphoma(CTCL), and is characterized by a clonal expansion of malignant CD4+ T lymphocytes with skinhoming properties. Clinically and pathologically, mycosis fungoides can be categorized into patch, plaque and tumor stages. The clinical course of mycosis fungoides is usually chronic and indolent, but a proportion of patients may develop progressive disease with peripheral blood, lymph node and visceral organ involvement. Sézarysyndrome is an aggressive leukemic form of CTCL characterized by a clonal population of malignant T cells in the peripheral blood. Various forms of skin-directed and systemic treatments are available for mycosis fungoides and Sézary syndrome. However, current treatments are generally not curative, and can only control the disease. Currently, the etiology and pathogenesis of mycosis fungoides and Sézary syndrome are not well defined. Proposed mechanisms include chronic antigenic stimulation by infectious agents, expression of specific adhesion molecules, altered cytokine production, mutations of oncogenes and tumor suppressor genes, and avoidance of apoptosis. In recent years, a number of chemokine receptors and their corresponding chemokine ligands have been found to contribute to the migration and survival of lymphoma cells in mycosis fungoides and Sézary syndrome, including CC chemokine receptor 4(CCR4), CCR10, C-X-C chemokine receptor type 4(CXCR4), CCR7, CCR3 and CXCR3. Since chemokines and chemokine receptors have been found to play important roles in the pathophysiology of mycosis fungoides and Sézary syndrome, they may be potentially useful targets for the development of new treatments for these diseases in the future.展开更多
Background: Histological evidence of lymph node involvement is associated with a poor prognosis in patients with cutaneous T-cell lymphoma (CTCL). Objectives: To determine whether T-cell receptor (TCR) gene analysis i...Background: Histological evidence of lymph node involvement is associated with a poor prognosis in patients with cutaneous T-cell lymphoma (CTCL). Objectives: To determine whether T-cell receptor (TCR) gene analysis is of prognostic relevance in CTCL. Methods: TCR gene analysis was performed on lymph node specimens from 60 patients with mycosis fungoides (MF) and Sézary syndrome (SS) using a highly sensitive polymerase chain reaction (PCR)/single-strand conformational polymorphism analysis and results were correlated with skin, overall clinical and histological lymph node stages. Results: The frequency with which a T-cell clone was detected in lymph node samples from patients with MF increased with skin stage, overall clinical stage and with the degree of histological involvement: six of 19 patients with uninvolved lymph nodes or limited histological involvement (LN0-2) and 13 of 14 patients with advanced histological involvement (LN3-4) had a detectable T-cell clone. In SS, 22 of 27 patients had a detectable lymph node T-cell clone. The clonal patients had a poorer prognosis than nonclonal patients (median survival from biopsy of > 72 months vs. 16 months for MF and 41.5 vs. 16.5 months for SS). Regression analysis confirmed that TCR gene analysis identifies a group of MF patients with a worse prognosis (P = 0.013). However, the molecular lymph node stage did not provide independent prognostic information in this cohort of patients in multivariate analysis. Conclusions: Molecular staging in MF and SS using a PCR-based method for TCR gene analysis provides additional information to histological examination. Specifically, this study identified a group of MF patients with early lymph node involvement with a poorer prognosis. However, a larger prospective study of patients with MF and early histological lymph node involvement is required to confirm whether molecular staging of lymph nodes provides independent prognostic information in a multivariate model.展开更多
Background. A 63-year-old man with therapy-resistant Se′ zary syndrome was enrolled in a multicenter trial of oral bexarotene for advanced-stage cutaneous T-cell lymphoma(CTCL). Methods. Monthly evaluations for effic...Background. A 63-year-old man with therapy-resistant Se′ zary syndrome was enrolled in a multicenter trial of oral bexarotene for advanced-stage cutaneous T-cell lymphoma(CTCL). Methods. Monthly evaluations for efficacy and side-effects were conducted and documented. Results. Gradual improvement in erythema, pruritus, and scale was noted during the initial 16week trial period and treatment was extended to 40 weeks. From week 20 to week 40, the erythroderma continued to improve and the lymph node burden decreased, but the absolute Se′ zary cell count inversely increased. By week 40, intractable pruritus and erythroderma abruptly recurred, and bexarotene was discontinued. Conclusions. Bexarotene is well tolerated and can be efficacious in patients with Se′ zary syndrome. Shifting of Se′ zary cells between different compartments was noted. Further studies on the interaction between the skin, lymph nodes, and peripheral blood compartments during bexarotene treatment in this subset of patients with CTCL are needed.展开更多
Background:Cutaneous T-cell lymphoma (CTCL) is a slowly progressive malignancy for which there is no cure. Therefore, accurate prediction of prognosis is important for the conduct of clinical trials and for counsellin...Background:Cutaneous T-cell lymphoma (CTCL) is a slowly progressive malignancy for which there is no cure. Therefore, accurate prediction of prognosis is important for the conduct of clinical trials and for counselling of individuals. Objectives:To improve prediction of survival in patients with CTCL. Methods:Prognostic factors including tumour-node-metastasis (TNM) criteria and the CTCL Severity Index (CTCL-SI) were analysed using a Weibull model for multivariate analysis in a sample of 62 patients with classical CTCL (mycosis fungoides and Sézary syndrome). The Brier score was used to quantify the quality of individual prediction. Results:Estimated 5-year survival rate (SR5) differed according to TNM stage:stage IA, 100%(95%confidence interval 70-100%); IB-III, 86%(73-100%); IVA, 54%(32-91%); IVB, 0%(0-52%). In a multivariate analysis, two independent prognostic factors were identified:lymph node (P=0.036) and blood involvement (P=0.015). A probability of survival model showed correlation of CTCL-SI with survival in patients with CTCL-SI > 20 according to the following formula:SR5 = 124-2×(CTCLSI)%. Calibration of SR5 against CTCL-SI-independent CTCL subsets revealed underestimation of Sézary syndrome. When CTCL-SI parameters were adjusted accordingly, the probability of survival model did not change significantly, while SR5 values became adequate. In addition, CTCL-SI was shown to be superior to TNM by 30%regarding individual predictive power. Conclusions:Probability of survival in CTCL can be accurately predicted by a CTCL-SI-based survival rate formula. Careful monitoring of lymph node and blood compartments and quantification by CTCL-SI are reliable tools for follow-up of patients with CTCL and allow progression-adjusted prediction of prognosis.展开更多
We describe a patient with erythrodermic adult T-cell leukaemia/ lymphoma resistant to multiple systemic therapies who, on the commencement of daclizumab, a humanized anti-interleukin-2 receptor antibody, developed a ...We describe a patient with erythrodermic adult T-cell leukaemia/ lymphoma resistant to multiple systemic therapies who, on the commencement of daclizumab, a humanized anti-interleukin-2 receptor antibody, developed a rapid and sustained complete response with resolution of previously debilitating erythroderma, suggesting significant activity of this agent in this disease process.展开更多
Background: A dominant T- cell clone can be detected by polymerase chain reaction (PCR) in 40- 90% of cutaneous samples from patients with cutaneous T- cell lymphoma (CTCL). Materials and methods: From 1996 to 2003 we...Background: A dominant T- cell clone can be detected by polymerase chain reaction (PCR) in 40- 90% of cutaneous samples from patients with cutaneous T- cell lymphoma (CTCL). Materials and methods: From 1996 to 2003 we analysed 547 cutaneous biopsies performed to exclude CTCL (mycosis fungoides, MF/Sé zary syndrome, SS). The final diagnosis was benign inflammatory disease (BID) in 353 samples (64.5% )- and CTCL in 194 (35.5% ). T- cell receptor (TCR)- γ gene rearrangement was studied by using a multiplex PCR/heteroduplex (HD) analysis. The PCR results were correlated with the clinical picture, the histological pattern and the presence of T- cell lineage antigen loss, using univariate and multivariate logistic regression analyses. Objective: To determine the sensitivity and specificity of the multiplex PCR/HD analysis and to identify which are the clinical, histopathological or immunophenotypical features significantly associated with a positive T- cell clonality. Results: A clonality was demonstrated in 83.5% of CTCL and in 2.3% of BID (P < 0.001). A significantly higher percentage of clonal cases was associated with the cutaneous T- score (71.4% in T1, 76.1% in T2 and 100% in nodular and erythrodermic MF samples) and with the presence of a T- cell lineage antigen loss (93.9% vs. 77.4% ). Moreover, clonality was closely related to an increase in the histopathological score (51.3% in the samples with a score < 5, compared with 92% in the lesions with ≥ 5). No significant difference in the percentage of clonal cases was found between T1/T2 and T3/T4 lesions with a histopathological score ≥ 5. The multivariate logistic regression showed that the density and extent of the cell infiltrate, the degree of epidermotropism and the presence of cytological atypia share an independent predictive value for clonality in T1/T2 samples, even if the highest odds ratios (3.6) were associated with the density of the cell infiltrate. The disease course of T1/T2 patients was analysed according to the PCR findings. All the PCR- negative patients showed a long- standing stable disease course; on the other hand, a disease progression occurred in 12/87 (13.8% ) positive patients. Conclusions: The multiplex PCR/HD analysis is associated with a high diagnostic accuracy (92.7% ) in CTCL patients. The finding of a clonal T- cell rearrangement is more closely associated with the histological pattern (in particular with the density and extent of the cell infiltrate) rather than with the MF cutaneous T- score or immunophenotype.展开更多
Several studies have investigated the possible involvement of viral agents,and among them herpes viruses,in the development of cutaneous T- cell lymphoma. The aim of our study was to determine whether T- cells specifi...Several studies have investigated the possible involvement of viral agents,and among them herpes viruses,in the development of cutaneous T- cell lymphoma. The aim of our study was to determine whether T- cells specific to Epstein- Barr virus(EBV)- antigens were detectable among tumor- infiltrating lymphocytes infiltrating cutaneous lesions of a patient with Sé zary syndrome. To analyze responses to EBV, we used a transient SV- 40 origin- defective transformed simian cells transfection assay that permits an estimation of CD8 T- cell responses against a large number of HLA/viral protein combinations. This technique allowed the detection of EBV- specific T lymphocytes mainly directed against epitopes generated during the lytic cycle in the cutaneous lesions. This is, to our knowledge,the first descrip- tion of the presence of EBV- specific T lymphocytes among tumor- infiltrating lymphocytes infiltrating the lesional skin of a patient with Sé zary syndrome.展开更多
Patients with Sé zary syndrome (SS) show clonal expansion in the peripheral blood of skin- homing CD4+ T- helper cells expressing cutaneous lymphocyte antigen (CLA). However, an increase of CLA+ CD4+ T cells can ...Patients with Sé zary syndrome (SS) show clonal expansion in the peripheral blood of skin- homing CD4+ T- helper cells expressing cutaneous lymphocyte antigen (CLA). However, an increase of CLA+ CD4+ T cells can also be observed in various inflammatory dermatoses. To facilitate early diagnosis and therapeutic monitoring of SS using flow cytometry, we evaluated the expression of CD7 and CD26 on the CLA+ CD4+ lymphocyte subset. Peripheral lymphocytes from 7 patients with SS, 16 patients with mycosis fungoides (MF) and 11 healthy controls were analysed by flow cytometry for the expression of CD4, CD7, CD26, CLA and CCR4. In addition, a longitudinal study was performed over 16 months in two patients with SS. Absence of CD7 and CD26 on CLA+ CD4+ T cells was highly specific for SS. Importantly, the absence of CD26 on CLA+ CD4+ T cells was very sensitive for SS, at 100% in our patient cohort. The number of CD26- CLA+ CD4+ T cells closely correlated with therapeutic interventions in the longitudinal analysis of two patients over more than 1 year. We conclude that the absence of CD26 expression on skin- homing CLA+ CD4+ T- helper cells is a very sensitive and highly specific parameter for early diagnosis and therapeutic monitoring of patients with SS.展开更多
Background: Because there are currently many effective therapies available for Sé zary syndrome, close monitoring of disease progression is required in order for a clinician to know when to institute or change an...Background: Because there are currently many effective therapies available for Sé zary syndrome, close monitoring of disease progression is required in order for a clinician to know when to institute or change an intervention. It has been our clinical experience that changes in patients’ CD4+ CD26- T- cell populations of peripheral blood lymphocytes herald changes in their clinical status. Objective: Our purpose was to evaluate whether a change in patients’ CD4+ CD26- population of T cells presages a change in their clinical status. We also sought to investigate the association between a change in Tcell populations that are CD4+ CD7- , CD8+ , CD56+ , and the CD4 + /CD8+ T- cell ratio and a change in the patient’ s clinical status. Methods: We conducted a retrospective chart review analysis of 21 patients with Sé zary syndrome who had flow cytometry, usually including levels of CD4+ CD26- , CD4+ CD7- , CD8+ , CD56+ , and CD4+ /CD8+ ratios measured at two time periods, 12 weeks apart. Results: We report two cases in which changes in patients’ clinical status were preceded by several weeks by a change in their CD4+ CD26- level. We report weak associations between a decreasing CD4+ CD26- T- cell population, a decreasing CD4+ CD7- population, an increasing CD56+ population, and an improving clinical status. We also report stronger associations between both a decreasing CD8+ population and an increasing CD4+ /CD8+ ratio and a worsening clinical status. Limitations: The study was limited by the number of patients and the time period over which the study was conducted. In addition, varying configurations of CD4+ CD26- T- cell populations were observed that may have limited the utility of this measurement. Conclusions: Flow cytometry assays of patients’ blood and, in particular, measurement of the CD4+ CD26- population of lymphocytes over time may be a valuable tool for monitoring patients with Sé zary syndrome. There exist varying configurations of CD26 T lymphocytes that may cause differences in standards for what is considered positive and negative between observers. Further prospective analysis involving larger groups of patients is recommended.展开更多
文摘Sézary syndrome(SS) is an aggressive variant of cutaneous T cell lymphoma characterized by the presence of malignant T cells in the skin, peripheral blood and lymph nodes. The tumoral population typically displays a CD3+ CD4+ CD45RO+ memory T cell phenotype. We report a case of SS with an aberrant CD56+ immunophenotype. This patient presented with a generalized erythroderma and palpable small axillary lymph nodes.SS(stage IVA) was diagnosed on histological criteria and by the detection of a major T cell clone in skin and blood, an elevated CD4/CD8 T cell ratio and Sézary cells count > 1000/mm3. Beside the Sézary cell marker KIR3DL2, immunostainings revealed that two third of the malignant cells expressed CD56 but no other natural killer(NK) cell marker such as CD16, CD160 or NKp46. This atypical expression was not linked to an activation-dependent process and remained stable during the time course of the disease. No loss of the panT-cell markers CD2, CD3 or CD4 was detected while a complete down-modulation of CD26 was observed. Despite several lines of treatment, no durable amelioration was observed and patient died after 10 mo of follow-up. Because this CD4+ CD56+ SS case is the only one reported so far, the functional significance of CD56 expression remained difficult to assess in terms of aggressiveness and prognosis.
文摘Mycosis fungoides is the most common form of cutaneous T-cell lymphoma(CTCL), and is characterized by a clonal expansion of malignant CD4+ T lymphocytes with skinhoming properties. Clinically and pathologically, mycosis fungoides can be categorized into patch, plaque and tumor stages. The clinical course of mycosis fungoides is usually chronic and indolent, but a proportion of patients may develop progressive disease with peripheral blood, lymph node and visceral organ involvement. Sézarysyndrome is an aggressive leukemic form of CTCL characterized by a clonal population of malignant T cells in the peripheral blood. Various forms of skin-directed and systemic treatments are available for mycosis fungoides and Sézary syndrome. However, current treatments are generally not curative, and can only control the disease. Currently, the etiology and pathogenesis of mycosis fungoides and Sézary syndrome are not well defined. Proposed mechanisms include chronic antigenic stimulation by infectious agents, expression of specific adhesion molecules, altered cytokine production, mutations of oncogenes and tumor suppressor genes, and avoidance of apoptosis. In recent years, a number of chemokine receptors and their corresponding chemokine ligands have been found to contribute to the migration and survival of lymphoma cells in mycosis fungoides and Sézary syndrome, including CC chemokine receptor 4(CCR4), CCR10, C-X-C chemokine receptor type 4(CXCR4), CCR7, CCR3 and CXCR3. Since chemokines and chemokine receptors have been found to play important roles in the pathophysiology of mycosis fungoides and Sézary syndrome, they may be potentially useful targets for the development of new treatments for these diseases in the future.
文摘Background: Histological evidence of lymph node involvement is associated with a poor prognosis in patients with cutaneous T-cell lymphoma (CTCL). Objectives: To determine whether T-cell receptor (TCR) gene analysis is of prognostic relevance in CTCL. Methods: TCR gene analysis was performed on lymph node specimens from 60 patients with mycosis fungoides (MF) and Sézary syndrome (SS) using a highly sensitive polymerase chain reaction (PCR)/single-strand conformational polymorphism analysis and results were correlated with skin, overall clinical and histological lymph node stages. Results: The frequency with which a T-cell clone was detected in lymph node samples from patients with MF increased with skin stage, overall clinical stage and with the degree of histological involvement: six of 19 patients with uninvolved lymph nodes or limited histological involvement (LN0-2) and 13 of 14 patients with advanced histological involvement (LN3-4) had a detectable T-cell clone. In SS, 22 of 27 patients had a detectable lymph node T-cell clone. The clonal patients had a poorer prognosis than nonclonal patients (median survival from biopsy of > 72 months vs. 16 months for MF and 41.5 vs. 16.5 months for SS). Regression analysis confirmed that TCR gene analysis identifies a group of MF patients with a worse prognosis (P = 0.013). However, the molecular lymph node stage did not provide independent prognostic information in this cohort of patients in multivariate analysis. Conclusions: Molecular staging in MF and SS using a PCR-based method for TCR gene analysis provides additional information to histological examination. Specifically, this study identified a group of MF patients with early lymph node involvement with a poorer prognosis. However, a larger prospective study of patients with MF and early histological lymph node involvement is required to confirm whether molecular staging of lymph nodes provides independent prognostic information in a multivariate model.
文摘Background. A 63-year-old man with therapy-resistant Se′ zary syndrome was enrolled in a multicenter trial of oral bexarotene for advanced-stage cutaneous T-cell lymphoma(CTCL). Methods. Monthly evaluations for efficacy and side-effects were conducted and documented. Results. Gradual improvement in erythema, pruritus, and scale was noted during the initial 16week trial period and treatment was extended to 40 weeks. From week 20 to week 40, the erythroderma continued to improve and the lymph node burden decreased, but the absolute Se′ zary cell count inversely increased. By week 40, intractable pruritus and erythroderma abruptly recurred, and bexarotene was discontinued. Conclusions. Bexarotene is well tolerated and can be efficacious in patients with Se′ zary syndrome. Shifting of Se′ zary cells between different compartments was noted. Further studies on the interaction between the skin, lymph nodes, and peripheral blood compartments during bexarotene treatment in this subset of patients with CTCL are needed.
文摘Background:Cutaneous T-cell lymphoma (CTCL) is a slowly progressive malignancy for which there is no cure. Therefore, accurate prediction of prognosis is important for the conduct of clinical trials and for counselling of individuals. Objectives:To improve prediction of survival in patients with CTCL. Methods:Prognostic factors including tumour-node-metastasis (TNM) criteria and the CTCL Severity Index (CTCL-SI) were analysed using a Weibull model for multivariate analysis in a sample of 62 patients with classical CTCL (mycosis fungoides and Sézary syndrome). The Brier score was used to quantify the quality of individual prediction. Results:Estimated 5-year survival rate (SR5) differed according to TNM stage:stage IA, 100%(95%confidence interval 70-100%); IB-III, 86%(73-100%); IVA, 54%(32-91%); IVB, 0%(0-52%). In a multivariate analysis, two independent prognostic factors were identified:lymph node (P=0.036) and blood involvement (P=0.015). A probability of survival model showed correlation of CTCL-SI with survival in patients with CTCL-SI > 20 according to the following formula:SR5 = 124-2×(CTCLSI)%. Calibration of SR5 against CTCL-SI-independent CTCL subsets revealed underestimation of Sézary syndrome. When CTCL-SI parameters were adjusted accordingly, the probability of survival model did not change significantly, while SR5 values became adequate. In addition, CTCL-SI was shown to be superior to TNM by 30%regarding individual predictive power. Conclusions:Probability of survival in CTCL can be accurately predicted by a CTCL-SI-based survival rate formula. Careful monitoring of lymph node and blood compartments and quantification by CTCL-SI are reliable tools for follow-up of patients with CTCL and allow progression-adjusted prediction of prognosis.
文摘We describe a patient with erythrodermic adult T-cell leukaemia/ lymphoma resistant to multiple systemic therapies who, on the commencement of daclizumab, a humanized anti-interleukin-2 receptor antibody, developed a rapid and sustained complete response with resolution of previously debilitating erythroderma, suggesting significant activity of this agent in this disease process.
文摘Background: A dominant T- cell clone can be detected by polymerase chain reaction (PCR) in 40- 90% of cutaneous samples from patients with cutaneous T- cell lymphoma (CTCL). Materials and methods: From 1996 to 2003 we analysed 547 cutaneous biopsies performed to exclude CTCL (mycosis fungoides, MF/Sé zary syndrome, SS). The final diagnosis was benign inflammatory disease (BID) in 353 samples (64.5% )- and CTCL in 194 (35.5% ). T- cell receptor (TCR)- γ gene rearrangement was studied by using a multiplex PCR/heteroduplex (HD) analysis. The PCR results were correlated with the clinical picture, the histological pattern and the presence of T- cell lineage antigen loss, using univariate and multivariate logistic regression analyses. Objective: To determine the sensitivity and specificity of the multiplex PCR/HD analysis and to identify which are the clinical, histopathological or immunophenotypical features significantly associated with a positive T- cell clonality. Results: A clonality was demonstrated in 83.5% of CTCL and in 2.3% of BID (P < 0.001). A significantly higher percentage of clonal cases was associated with the cutaneous T- score (71.4% in T1, 76.1% in T2 and 100% in nodular and erythrodermic MF samples) and with the presence of a T- cell lineage antigen loss (93.9% vs. 77.4% ). Moreover, clonality was closely related to an increase in the histopathological score (51.3% in the samples with a score < 5, compared with 92% in the lesions with ≥ 5). No significant difference in the percentage of clonal cases was found between T1/T2 and T3/T4 lesions with a histopathological score ≥ 5. The multivariate logistic regression showed that the density and extent of the cell infiltrate, the degree of epidermotropism and the presence of cytological atypia share an independent predictive value for clonality in T1/T2 samples, even if the highest odds ratios (3.6) were associated with the density of the cell infiltrate. The disease course of T1/T2 patients was analysed according to the PCR findings. All the PCR- negative patients showed a long- standing stable disease course; on the other hand, a disease progression occurred in 12/87 (13.8% ) positive patients. Conclusions: The multiplex PCR/HD analysis is associated with a high diagnostic accuracy (92.7% ) in CTCL patients. The finding of a clonal T- cell rearrangement is more closely associated with the histological pattern (in particular with the density and extent of the cell infiltrate) rather than with the MF cutaneous T- score or immunophenotype.
文摘Several studies have investigated the possible involvement of viral agents,and among them herpes viruses,in the development of cutaneous T- cell lymphoma. The aim of our study was to determine whether T- cells specific to Epstein- Barr virus(EBV)- antigens were detectable among tumor- infiltrating lymphocytes infiltrating cutaneous lesions of a patient with Sé zary syndrome. To analyze responses to EBV, we used a transient SV- 40 origin- defective transformed simian cells transfection assay that permits an estimation of CD8 T- cell responses against a large number of HLA/viral protein combinations. This technique allowed the detection of EBV- specific T lymphocytes mainly directed against epitopes generated during the lytic cycle in the cutaneous lesions. This is, to our knowledge,the first descrip- tion of the presence of EBV- specific T lymphocytes among tumor- infiltrating lymphocytes infiltrating the lesional skin of a patient with Sé zary syndrome.
文摘Patients with Sé zary syndrome (SS) show clonal expansion in the peripheral blood of skin- homing CD4+ T- helper cells expressing cutaneous lymphocyte antigen (CLA). However, an increase of CLA+ CD4+ T cells can also be observed in various inflammatory dermatoses. To facilitate early diagnosis and therapeutic monitoring of SS using flow cytometry, we evaluated the expression of CD7 and CD26 on the CLA+ CD4+ lymphocyte subset. Peripheral lymphocytes from 7 patients with SS, 16 patients with mycosis fungoides (MF) and 11 healthy controls were analysed by flow cytometry for the expression of CD4, CD7, CD26, CLA and CCR4. In addition, a longitudinal study was performed over 16 months in two patients with SS. Absence of CD7 and CD26 on CLA+ CD4+ T cells was highly specific for SS. Importantly, the absence of CD26 on CLA+ CD4+ T cells was very sensitive for SS, at 100% in our patient cohort. The number of CD26- CLA+ CD4+ T cells closely correlated with therapeutic interventions in the longitudinal analysis of two patients over more than 1 year. We conclude that the absence of CD26 expression on skin- homing CLA+ CD4+ T- helper cells is a very sensitive and highly specific parameter for early diagnosis and therapeutic monitoring of patients with SS.
文摘Background: Because there are currently many effective therapies available for Sé zary syndrome, close monitoring of disease progression is required in order for a clinician to know when to institute or change an intervention. It has been our clinical experience that changes in patients’ CD4+ CD26- T- cell populations of peripheral blood lymphocytes herald changes in their clinical status. Objective: Our purpose was to evaluate whether a change in patients’ CD4+ CD26- population of T cells presages a change in their clinical status. We also sought to investigate the association between a change in Tcell populations that are CD4+ CD7- , CD8+ , CD56+ , and the CD4 + /CD8+ T- cell ratio and a change in the patient’ s clinical status. Methods: We conducted a retrospective chart review analysis of 21 patients with Sé zary syndrome who had flow cytometry, usually including levels of CD4+ CD26- , CD4+ CD7- , CD8+ , CD56+ , and CD4+ /CD8+ ratios measured at two time periods, 12 weeks apart. Results: We report two cases in which changes in patients’ clinical status were preceded by several weeks by a change in their CD4+ CD26- level. We report weak associations between a decreasing CD4+ CD26- T- cell population, a decreasing CD4+ CD7- population, an increasing CD56+ population, and an improving clinical status. We also report stronger associations between both a decreasing CD8+ population and an increasing CD4+ /CD8+ ratio and a worsening clinical status. Limitations: The study was limited by the number of patients and the time period over which the study was conducted. In addition, varying configurations of CD4+ CD26- T- cell populations were observed that may have limited the utility of this measurement. Conclusions: Flow cytometry assays of patients’ blood and, in particular, measurement of the CD4+ CD26- population of lymphocytes over time may be a valuable tool for monitoring patients with Sé zary syndrome. There exist varying configurations of CD26 T lymphocytes that may cause differences in standards for what is considered positive and negative between observers. Further prospective analysis involving larger groups of patients is recommended.
