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 .