Document Detail

The relevance of peripheral blood T-helper 1 and 2 cytokine pattern in the evaluation of patients with mycosis fungoides and Sézary syndrome.
MedLine Citation:
PMID:  12752128     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: There is evidence that a T-helper (Th) 2 cytokine pattern dominates in the peripheral blood as well as in tissue of patients with Sézary syndrome (SS), and that the malignant clone is of Th2 phenotype. However, there are conflicting studies on the cytokine pattern in the peripheral blood in different stages of cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To examine, by means of flow cytometry (FC), the Th1/Th2 cytokine profile [cytoplasmic interferon (IFN)-gamma/interleukin (IL)-4] in peripheral blood T cells from patients with mycosis fungoides (MF) and SS, the most common forms of CTCL, and to correlate their expression with clinical stage, clonality and T-cell immunophenotype changes in order to evaluate their relevance in CTCL progression. METHODS: We investigated by FC the percentage of CD3+ T cells expressing cytoplasmic IFN-gamma and IL-4 after stimulation in blood specimens of 43 CTCL patients (32 stage I-II and 11 stage III-IV), eight of whom were erythrodermic. Next, we compared cytoplasmic IFN-gamma and IL-4 expression between patients of different stages and controls, and correlated our findings to T-cell receptor (TCR)-gamma gene rearrangement, used as a marker of clonality, and changes in T-cell immunophenotype (CD4+, CD8+, CD4+/CD7-, CD4+/CD25+) and natural killer cells. Polymerase chain reaction amplification of the TCR-gamma gene was performed in 41 blood and 26 skin specimens. We also examined the cytokine expression pattern in patients with erythrodermic MF and SS. RESULTS: A significantly higher frequency of CD3+/IL-4+ T cells was found in late (III-IV) compared with early (I-II) CTCL patients (P = 0.002) or controls (P < 0.001). There were significant positive correlations between the percentages of CD3+/IL-4+ and the percentages of CD3+/CD4+ T cells (r = 0.385, P = 0.05), CD4+/CD7- T cells (r = 0.335, P < 0.05) and CD4+/CD25+ T cells (r = 0.433, P = 0.01); there was a negative correlation between the percentages of CD3+/IL-4+ and CD3+/CD8+ T cells (r = -0.463, P = 0.005) and a positive correlation between the percentages of CD3+/IFN-gamma+ and CD3+/CD8+ T cells (r = 0.368, P = 0.02). Increased percentages of CD3+/IL-4+, CD3+/CD4+ and CD4+/CD7- T lymphocytes were associated with the presence of clonality (P = 0.025, P < 0.001 and P = 0.0031, respectively). All independent variables showed a statistically significant difference between SS and erythrodermic MF patients, or controls, apart from cytoplasmic IL-4, which was high both in erythrodermic MF and SS patients compared with controls (P = 0.003 and P = 0.008, respectively). In multiple regression logistic analysis, the probability of belonging to advanced CTCL stages was associated only with increased cytoplasmic IL-4 (P = 0.007, odds ratio 1.13, 95% confidence interval 1.033-1.229). CONCLUSIONS: Increased T-cell cytoplasmic IL-4 is more frequent in late CTCL stages, correlates with T-cell immunophenotype changes found in advanced disease and is associated with clonality. Increased cytoplasmic IL-4 is frequent both in erythrodermic MF and SS patients, in contrast to other variables found increased only in SS, suggesting that IL-4 may be an early indicator of disease progression. Moreover, our results show that increased cytoplasmic IL-4 is the sole predictor of advanced CTCL disease and confirm the relevance of FC determination of IL-4 in the routine evaluation of CTCL cases.
E Papadavid; J Economidou; A Psarra; V Kapsimali; V Mantzana; C Antoniou; K Limas; A Stratigos; N Stavrianeas; G Avgerinou; A Katsambas
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The British journal of dermatology     Volume:  148     ISSN:  0007-0963     ISO Abbreviation:  Br. J. Dermatol.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-05-19     Completed Date:  2003-07-29     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0004041     Medline TA:  Br J Dermatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  709-18     Citation Subset:  IM    
Department of Dermatology and Venereology of the University of Athens, A.Syngros Hospital, Athens, Greece.
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MeSH Terms
Aged, 80 and over
Flow Cytometry
Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / immunology
Interferon-gamma / blood*
Interleukin-4 / blood*
Logistic Models
Middle Aged
Mycosis Fungoides / immunology*,  pathology
Neoplasm Staging
Sezary Syndrome / immunology*
Skin Neoplasms / immunology*,  pathology
T-Lymphocyte Subsets / immunology
T-Lymphocytes, Helper-Inducer / immunology*
Reg. No./Substance:
207137-56-2/Interleukin-4; 82115-62-6/Interferon-gamma

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