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Sequential decisions on FAS sequencing guided by biomarkers in patients with lymphoproliferation and autoimmune cytopenia

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Sequential decisions on FAS sequencing guided by biomarkers in patients with lymphoproliferation and autoimmune cytopenia. / Rensing-Ehl, Anne; Janda, Ales; Lorenz, Myriam R; Gladstone, Beryl P; Fuchs, Ilka; Abinun, Mario; Albert, Michael; Butler, Karina; Cant, Andrew; Cseh, Anna-Maria; Ebinger, Martin; Goldacker, Sigune; Hambleton, Sophie; Hebart, Holger; Houet, Leonora; Kentouche, Karim; Kühnle, Ingrid; Lehmberg, Kai; Mejstrikova, Ester; Niemeyer, Charlotte; Minkov, Milen; Neth, Olaf; Dückers, Gregor; Owens, Stephan; Rösler, Joachim; Schilling, Freimut H; Schuster, Volker; Seidel, Markus G; Smisek, Petr; Sukova, Martina; Svec, Peter; Wiesel, Thomas; Gathmann, Benjamin; Schwarz, Klaus; Vach, Werner; Ehl, Stephan; Speckmann, Carsten.

In: HAEMATOLOGICA, Vol. 98, No. 12, 01.12.2013, p. 1948-55.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Rensing-Ehl, A, Janda, A, Lorenz, MR, Gladstone, BP, Fuchs, I, Abinun, M, Albert, M, Butler, K, Cant, A, Cseh, A-M, Ebinger, M, Goldacker, S, Hambleton, S, Hebart, H, Houet, L, Kentouche, K, Kühnle, I, Lehmberg, K, Mejstrikova, E, Niemeyer, C, Minkov, M, Neth, O, Dückers, G, Owens, S, Rösler, J, Schilling, FH, Schuster, V, Seidel, MG, Smisek, P, Sukova, M, Svec, P, Wiesel, T, Gathmann, B, Schwarz, K, Vach, W, Ehl, S & Speckmann, C 2013, 'Sequential decisions on FAS sequencing guided by biomarkers in patients with lymphoproliferation and autoimmune cytopenia', HAEMATOLOGICA, vol. 98, no. 12, pp. 1948-55. https://doi.org/10.3324/haematol.2012.081901

APA

Rensing-Ehl, A., Janda, A., Lorenz, M. R., Gladstone, B. P., Fuchs, I., Abinun, M., Albert, M., Butler, K., Cant, A., Cseh, A-M., Ebinger, M., Goldacker, S., Hambleton, S., Hebart, H., Houet, L., Kentouche, K., Kühnle, I., Lehmberg, K., Mejstrikova, E., ... Speckmann, C. (2013). Sequential decisions on FAS sequencing guided by biomarkers in patients with lymphoproliferation and autoimmune cytopenia. HAEMATOLOGICA, 98(12), 1948-55. https://doi.org/10.3324/haematol.2012.081901

Vancouver

Rensing-Ehl A, Janda A, Lorenz MR, Gladstone BP, Fuchs I, Abinun M et al. Sequential decisions on FAS sequencing guided by biomarkers in patients with lymphoproliferation and autoimmune cytopenia. HAEMATOLOGICA. 2013 Dec 1;98(12):1948-55. https://doi.org/10.3324/haematol.2012.081901

Bibtex

@article{55ce261358f64eb2ba2e5c2bbbb46de7,
title = "Sequential decisions on FAS sequencing guided by biomarkers in patients with lymphoproliferation and autoimmune cytopenia",
abstract = "Clinical and genetic heterogeneity renders confirmation or exclusion of autoimmune lymphoproliferative syndrome difficult. To re-evaluate and improve the currently suggested diagnostic approach to patients with suspected FAS mutation, the most frequent cause of autoimmune lymphoproliferative syndrome, we prospectively determined 11 biomarkers in 163 patients with splenomegaly or lymphadenopathy and presumed or proven autoimmune cytopenia(s). Among 98 patients sequenced for FAS mutations in CD3(+)TCRα/β(+)CD4(-)CD8(-) {"}double negative{"} T cells, 32 had germline and six had somatic FAS mutations. The best a priori predictor of FAS mutations was the combination of vitamin B12 and soluble FAS ligand (cut-offs 1255 pg/mL and 559 pg/mL, respectively), which had a positive predictive value of 92% and a negative predictive value of 97%. We used these data to develop a web-based probability calculator for FAS mutations using the three most discriminatory biomarkers (vitamin B12, soluble FAS ligand, interleukin-10) of the 11 tested. Since more than 60% of patients with lymphoproliferation and autoimmune cytopenia(s) in our cohort did not harbor FAS mutations, 15% had somatic FAS mutations, and the predictive value of double-negative T-cell values was rather low (positive and negative predictive values of 61% and 77%, respectively), we argue that the previously suggested diagnostic algorithm based on determination of double-negative T cells and germline FAS sequencing, followed by biomarker analysis, is not efficient. We propose vitamin B12 and soluble FAS ligand assessment as the initial diagnostic step with subsequent decision on FAS sequencing supported by a probability-calculating tool.",
author = "Anne Rensing-Ehl and Ales Janda and Lorenz, {Myriam R} and Gladstone, {Beryl P} and Ilka Fuchs and Mario Abinun and Michael Albert and Karina Butler and Andrew Cant and Anna-Maria Cseh and Martin Ebinger and Sigune Goldacker and Sophie Hambleton and Holger Hebart and Leonora Houet and Karim Kentouche and Ingrid K{\"u}hnle and Kai Lehmberg and Ester Mejstrikova and Charlotte Niemeyer and Milen Minkov and Olaf Neth and Gregor D{\"u}ckers and Stephan Owens and Joachim R{\"o}sler and Schilling, {Freimut H} and Volker Schuster and Seidel, {Markus G} and Petr Smisek and Martina Sukova and Peter Svec and Thomas Wiesel and Benjamin Gathmann and Klaus Schwarz and Werner Vach and Stephan Ehl and Carsten Speckmann",
year = "2013",
month = dec,
day = "1",
doi = "10.3324/haematol.2012.081901",
language = "English",
volume = "98",
pages = "1948--55",
journal = "HAEMATOLOGICA",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "12",

}

RIS

TY - JOUR

T1 - Sequential decisions on FAS sequencing guided by biomarkers in patients with lymphoproliferation and autoimmune cytopenia

AU - Rensing-Ehl, Anne

AU - Janda, Ales

AU - Lorenz, Myriam R

AU - Gladstone, Beryl P

AU - Fuchs, Ilka

AU - Abinun, Mario

AU - Albert, Michael

AU - Butler, Karina

AU - Cant, Andrew

AU - Cseh, Anna-Maria

AU - Ebinger, Martin

AU - Goldacker, Sigune

AU - Hambleton, Sophie

AU - Hebart, Holger

AU - Houet, Leonora

AU - Kentouche, Karim

AU - Kühnle, Ingrid

AU - Lehmberg, Kai

AU - Mejstrikova, Ester

AU - Niemeyer, Charlotte

AU - Minkov, Milen

AU - Neth, Olaf

AU - Dückers, Gregor

AU - Owens, Stephan

AU - Rösler, Joachim

AU - Schilling, Freimut H

AU - Schuster, Volker

AU - Seidel, Markus G

AU - Smisek, Petr

AU - Sukova, Martina

AU - Svec, Peter

AU - Wiesel, Thomas

AU - Gathmann, Benjamin

AU - Schwarz, Klaus

AU - Vach, Werner

AU - Ehl, Stephan

AU - Speckmann, Carsten

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Clinical and genetic heterogeneity renders confirmation or exclusion of autoimmune lymphoproliferative syndrome difficult. To re-evaluate and improve the currently suggested diagnostic approach to patients with suspected FAS mutation, the most frequent cause of autoimmune lymphoproliferative syndrome, we prospectively determined 11 biomarkers in 163 patients with splenomegaly or lymphadenopathy and presumed or proven autoimmune cytopenia(s). Among 98 patients sequenced for FAS mutations in CD3(+)TCRα/β(+)CD4(-)CD8(-) "double negative" T cells, 32 had germline and six had somatic FAS mutations. The best a priori predictor of FAS mutations was the combination of vitamin B12 and soluble FAS ligand (cut-offs 1255 pg/mL and 559 pg/mL, respectively), which had a positive predictive value of 92% and a negative predictive value of 97%. We used these data to develop a web-based probability calculator for FAS mutations using the three most discriminatory biomarkers (vitamin B12, soluble FAS ligand, interleukin-10) of the 11 tested. Since more than 60% of patients with lymphoproliferation and autoimmune cytopenia(s) in our cohort did not harbor FAS mutations, 15% had somatic FAS mutations, and the predictive value of double-negative T-cell values was rather low (positive and negative predictive values of 61% and 77%, respectively), we argue that the previously suggested diagnostic algorithm based on determination of double-negative T cells and germline FAS sequencing, followed by biomarker analysis, is not efficient. We propose vitamin B12 and soluble FAS ligand assessment as the initial diagnostic step with subsequent decision on FAS sequencing supported by a probability-calculating tool.

AB - Clinical and genetic heterogeneity renders confirmation or exclusion of autoimmune lymphoproliferative syndrome difficult. To re-evaluate and improve the currently suggested diagnostic approach to patients with suspected FAS mutation, the most frequent cause of autoimmune lymphoproliferative syndrome, we prospectively determined 11 biomarkers in 163 patients with splenomegaly or lymphadenopathy and presumed or proven autoimmune cytopenia(s). Among 98 patients sequenced for FAS mutations in CD3(+)TCRα/β(+)CD4(-)CD8(-) "double negative" T cells, 32 had germline and six had somatic FAS mutations. The best a priori predictor of FAS mutations was the combination of vitamin B12 and soluble FAS ligand (cut-offs 1255 pg/mL and 559 pg/mL, respectively), which had a positive predictive value of 92% and a negative predictive value of 97%. We used these data to develop a web-based probability calculator for FAS mutations using the three most discriminatory biomarkers (vitamin B12, soluble FAS ligand, interleukin-10) of the 11 tested. Since more than 60% of patients with lymphoproliferation and autoimmune cytopenia(s) in our cohort did not harbor FAS mutations, 15% had somatic FAS mutations, and the predictive value of double-negative T-cell values was rather low (positive and negative predictive values of 61% and 77%, respectively), we argue that the previously suggested diagnostic algorithm based on determination of double-negative T cells and germline FAS sequencing, followed by biomarker analysis, is not efficient. We propose vitamin B12 and soluble FAS ligand assessment as the initial diagnostic step with subsequent decision on FAS sequencing supported by a probability-calculating tool.

U2 - 10.3324/haematol.2012.081901

DO - 10.3324/haematol.2012.081901

M3 - SCORING: Journal article

C2 - 23850805

VL - 98

SP - 1948

EP - 1955

JO - HAEMATOLOGICA

JF - HAEMATOLOGICA

SN - 0390-6078

IS - 12

ER -