834 CLINICAL REPORT
ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
High Expression of Fas / CD95 on CD4 + Circulating T Cells: An Exclusion Criterion in the Diagnosis of Mycosis Fungoides?
Aurélie DU-THANH 1, Pierre PORTALÈS 2, Anne SERRE-COUSINÉ 1, Céline GIRARD 1, Bernard GUILLOT 1 and Olivier DEREURE 1
1
Department of Dermatology, University of Montpellier and INSERM U1058, and 2 Laboratory of Immunology, University of Montpellier, Montpellier, France
The aim of this 10-year monocentric prospective study was to determine a cut-off value of Fas / CD95 expression by peripheral blood CD4 + T lymphocytes in discriminating patients with mycosis fungoides from controls with cutaneous benign lymphocytic conditions. CD95 expression in peripheral blood CD4 + T lymphocytes was measured using flow cytometry in 330 patients referred for diagnosis: 104 with mycosis fungoides and 226 with eczema, psoriasis, drug reaction, etc. The sensitivity and specificity of different thresholds of CD95 expression were calculated regarding the final diagnosis of patients with mycosis fungoides or controls. CD95 expression higher than 30 % reached a specificity of 91 % in ruling out a diagnosis of mycosis fungoides, although overall CD95 expression was not significantly different from that of controls( p = 0.309) and sensitivity was very low( 5 %). Thus, peripheral CD95 expression higher than 30 % could be used among the exclusion criteria in a multicomponent score for mycosis fungoides diagnosis.
Key words: mycosis fungoides; Fas / Fas ligand system; peripheral blood CD4 + CD95 + rate; CD95 expression.
Accepted Feb 15, 2017; Epub ahead of print Feb 16, 2017 Acta Derm Venereol 2017; 97: 834 – 837.
Corr: Aurélie Du-Thanh, Department of Dermatology, University of Montpellier and INSERM U1058, Hôpital Saint-Eloi, 80 avenue Augustin Fliche, FR-34295 Montpellier cedex 5, France. E-mail: a-du _ thanh @ chu-montpellier. fr
The pathogenesis of mycosis fungoides( MF), the major subset of cutaneous T-cell lymphomas( CTCL), is largely unknown. Functional abnormalities of postactivation T-cell apoptosis have been suggested as initial pathomechanisms of MF. Specifically, an acquired impairment of the Fas / Fas ligand system could lead to a slow, but continuous, accumulation of non-proliferative, skin-addressed T cells( 1). Fas, also called CD95, is a transmembrane protein belonging to the tumour necrosis factor superfamily, and is physiologically expressed on the surface of activated B- and T cells. Binding of Fas to Fas ligand activates the death-inducing signalling complex, which ultimately results in cell apoptosis through complex pathways mainly involving the activation of downstream caspases( 2). In MF, inactivating mutations of the fas gene coding sequence, resulting in the production of an inefficient molecule or epigenetic changes with hypermethylation of the promoter region of this gene, leading to transcriptional down-regulation, have been reported( 3 – 5).
Early diagnosis of MF, however, remains significantly challenging, due to the frequent lack of specific clinical and histological criteria at this stage resulting in delay in diagnosis and relevant care in many patients( 6). The identification of T-cell clonal expansion in skin lesions, using molecular biology techniques, enabled a major improvement in early diagnosis; however, this approach does not always lead to a clear-cut conclusion. In an effort to circumvent this difficulty, the International Society for Cutaneous Lymphomas( ISCL) proposed a semi-quantitative score to help the early diagnosis of MF, based on clinical, histopathological, immunophenotyping and molecular criteria( 7), although uncertain situations remain frequent. Thus, the search for additional, easy to implement diagnostic criteria that can also be used in difficult, ill-defined cutaneous T-cell infiltrates remains a relevant issue.
Previous studies, although limited in size, showed a significant reduction in the percentage of circulating CD4 + T-cell lymphocytes also expressing CD95( CD4 + CD95 + / CD4 + ratio) in some patients with CTCL compared with cutaneous benign lymphocytic conditions( BLC) although the underlying mechanisms remain questionable; an attractive hypothesis would be the presence of a specific additional CD4 + CD95-population closely related to circulating clonal, neoplastic lymphocytes displaying fas gene abnormalities( either through mutations or epigenetic changes) resulting in a lack of expression of CD95 on the cell surface. This interpretation is consistent with the demonstration of the presence of the tumoural T-cell clone in peripheral blood in a significant number of early stages of MF. Moreover, immunochemistry studies showed that neoplastic T cells in CTCL skin lesions may also underexpress CD95( 3, 8, 9).
Based on these previous, although limited, data, a prospective, large-scale study was designed to extend these preliminary results. The aims of this study were to investigate the possibly discriminating value of CD95 expression level by CD4 + circulating T lymphocytes between MF and BLC, and to assess the sensitivity and specificity of putative cut-off values of this CD4 + CD95 + / CD4 + ratio in the differential diagnosis of MF vs. BLC. doi: 10.2340 / 00015555-2632 Acta Derm Venereol 2017; 97: 834 – 837
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica.