Monoclonal T-Cell Dyscrasia of Undetermined Significance Associated With Recalcitrant Erythroderma

Gniadecki, Robert; Lukowsky, Ansgar

doi:10.1001/archderm.141.3.361

Cited by 40 publications

(21 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Instead, this monoclonal expansion of T-cells may represent another example of a T-cell counterpart to a MGUS, which is a benign gammopathy, presumably arising from chronic stimulation of B-cells by self-antigens or microbial antigens over a lifetime [31]. Such monoclonal T-cell expansions of undetermined significance (MTUS) have already been described before [32][33][34] and were particularly frequent in the elderly [32]; up to now, however, the antigenic specificities of those T-cells were not identified. In that respect, together with the absence of any definite M. tuberculosis-related morbidity, the monoclonal T-cell response directed against peptide E2 of ESAT-6 may represent the first MTUS where the antigenic specificity is known.…”

Section: Discussionmentioning

confidence: 96%

Massive monoclonal expansion of CD4 T-cells specific for aMycobacterium tuberculosisESAT-6 peptide

Hodapp

Sester²,

Mack³

et al. 2012

Eur Respir J

View full text Add to dashboard Cite

T-cell responses towards tuberculin (purified protein derivative; PPD) or the Mycobacterium tuberculosis-specific antigens early secretory antigenic target (ESAT)-6 and culture filtrate protein-10 are indicative of prior contact with mycobacterial antigens. In this study, we investigated the exceptional case of a 75-yr-old patient who devoted more than one-third of his CD4 T-cells against PPD and ESAT-6.Antigen-specific T-cells were characterised using flow cytometric intracellular cytokine staining, ELISPOT assay, proliferation assays, and T-cell receptor spectratyping.T-cell frequencies were far above those found in age-matched controls (median 0.33%, range 0.05-6.32%) and remained at high levels for .2 yrs. The patient initially presented with haemoptysis, but active tuberculosis was ruled out by repeated analysis of sputum and bronchoalveolar lavage fluid. Skin testing was negative and haemoptyses did not have a M. tuberculosis-related aetiology. Phenotypical and functional properties of specific T-cells were consistent with a terminally differentiated effector-memory phenotype with capacity to produce interferon-c, interleukin-2 and tumour necrosis factor-a. Epitope mapping showed that the CD4 T-cells were directed against a single peptide from ESAT-6 (amino acid 5-20) that was presented in context of HLA-DR. T-cell receptor Vb-spectratyping and sequencing of specific CD4 T-cells revealed a prominent peak fraction of monoclonal origin.In conclusion, similar to monoclonal gammopathies of undetermined significance, this may represent the first T-cell counterpart with known specificity against M. tuberculosis.

show abstract

Section: Discussionmentioning

confidence: 96%

Massive monoclonal expansion of CD4 T-cells specific for aMycobacterium tuberculosisESAT-6 peptide

Hodapp

Sester²,

Mack³

et al. 2012

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…However, detection of identical clones from two different sites is quite specific for MF [112]. The extent to which MF/SS may be preceded by a premalignant state, analogous to monoclonal B-cell lymphocytosis (MBL) or monoclonal gammopathy of undetermined significance (MGUS), is debatable and poorly defined [113]. The malignant lymphocytes in MF/SS are usually CD3 1 CD4 1 and CD8 2 , but frequently lose the expression of other pan-Tcell antigens.…”

Section: American Journal Of Hematology 931mentioning

confidence: 99%

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

Wilcox

2011

American J Hematol

View full text Add to dashboard Cite

Disease overview: Cutaneous T‐cell lymphomas are a heterogenous group of T‐cell lymphoproliferative disorders involving the skin, the majority of which may be classified as Mycosis fungoides (MF) or Sézary syndrome (SS).Diagnosis: The diagnosis of MF or SS requires the integration of clinical and histopathologic data.Risk‐adapted therapy: Tumor, node, metastasis, and blood (TNMB) staging remains the most important prognostic factor in MF/SS and forms the basis for a “risk‐adapted,” multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin‐directed therapies is preferred, as both disease‐specific and overall survival for these patients is favorable. In contrast, patients with advanced‐stage disease with significant nodal, visceral, or blood involvement are generally approached with biologic‐response modifiers, denileukin diftitox, and histone deacetylase inhibitors before escalating therapy to include systemic, single‐agent chemotherapy. Multiagent chemotherapy may be used for those patients with extensive visceral involvement requiring rapid disease control. In highly‐selected patients with disease refractory to standard treatments, allogeneic stem‐cell transplantation may be considered. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.

show abstract

“…[20][21][22][23] The term 'T-cell expansion of undetermined significance,' analogous to monoclonal gammopathy of undetermined significance, has been suggested for the presence of a small monoclonal T-cell population in an otherwise healthy individual, usually over 60 years of age. 24 Because of these diagnostic difficulties, the International Society for Cutaneous Lymphomas/European Organization for Research and Treatment of Cancer tried to simplify and clarify the definitions of low-level peripheral blood involvement in their staging system. 6 In stage B0, Sézary cells comprise o5% of the nucleated cells, whereas in stage B1 Sézary cells are 45% but o1.0 K/ml, or Z1.0 K/ml but negative for monoclonal T-cell receptor gene rearrangement.…”

mentioning

confidence: 99%

Flow cytometric detection of peripheral blood involvement by mycosis fungoides and Sézary syndrome using T-cell receptor Vβ chain antibodies and its application in blood staging

et al. 2010

View full text Add to dashboard Cite

Peripheral blood involvement has been recognized as an adverse prognostic factor in patients with mycosis fungoides and Sé zary syndrome. However, accurate identification and enumeration of the neoplastic cells in these diseases can be challenging. We assessed the clinical utility of flow cytometric immunophenotypic analysis of T-cell receptor Vb expression in 82 mycosis fungoides and 6 Sé zary syndrome patients, with an atypical T-cell immunophenotype, or abnormal CD4:CD8 ratio, identified from peripheral blood specimens of 723 patients submitted for routine mycosis fungoides/Sé zary syndrome blood staging. To improve detection sensitivity, Vb expression was analyzed on gated CD3 þ CD4 þ T cells or T cells with an aberrant immunophenotype, if present. The flow cytometric results were compared with traditional morphologic assessment (n ¼ 88) and molecular methods to assess the T-cell receptor c or b genes (n ¼ 41 tested in parallel). Flow cytometric immunophenotyping yielded a clonal Vb pattern in 60/82 mycosis fungoides and 6/6 Sé zary syndrome patients. By contrast, flow cytometric Vb was negative in all 10 healthy donors and 18 control patients, showing a specificity of 100% and concordance with molecular testing of 86%. Using flow cytometric Vb results instead of morphologic assessment, 12 patients were upstaged from B1 to B2, and 20 patients from B0 to B1 (Po0.0001). The 12 upstaged B2 patients had no morphologic evidence of involvement, but had an aggressive clinical course similar to those staged by traditional morphologic assessment (median survival 27 vs 41 months, log-rank P ¼ 0.701). In 30/44 patients with a tumor-associated Vb expression, a single Vb tube was used to monitor treatment response. In conclusion, flow cytometric Vb analysis is rapid and convenient, can assess T-cell clonality and tumor quantity simultaneously, and is useful both in initial blood staging and monitoring tumor burden during therapy in patients with mycosis fungoides or Sé zary syndrome.

show abstract

Monoclonal T-Cell Dyscrasia of Undetermined Significance Associated With Recalcitrant Erythroderma

Cited by 40 publications

References 45 publications

Massive monoclonal expansion of CD4 T-cells specific for aMycobacterium tuberculosisESAT-6 peptide

Massive monoclonal expansion of CD4 T-cells specific for aMycobacterium tuberculosisESAT-6 peptide

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

Flow cytometric detection of peripheral blood involvement by mycosis fungoides and Sézary syndrome using T-cell receptor Vβ chain antibodies and its application in blood staging

Contact Info

Product

Resources

About