TY - JOUR
T1 - Biological stratification of clinical disease courses in childhood immune thrombocytopenia
AU - Schmidt, David E.
AU - Heitink-Pollé, Katja M. J.
AU - Mertens, Bart
AU - Porcelijn, Leendert
AU - Kapur, Rick
AU - van der Schoot, C. Ellen
AU - Vidarsson, Gestur
AU - van der Bom, Johanna G.
AU - Bruin, Marrie C. A.
AU - de Haas, Masja
N1 - Funding Information: We are particularly grateful to Laurens Bosman (University Medical Center Utrecht) for discussions regarding statistical modelling. This study would not have been possible without the dedicated teams at the central laboratory of this study; of the Laboratory of Platelet Serology, Sanquin Diagnostics, in particular Elly Huiskes; and the team of the Immunocytology Laboratory, Sanquin Diagnostics, in particular Christa Homburg. The study was supported by a research grant from the Landsteiner Foundation for Blood Transfusion Research (LSBR), a doctoral stipend to D.E.S. by the Studienstiftung des Deutschen Volkes, and Wilhelmina Children?s Hospital Utrecht. Publisher Copyright: © 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis
PY - 2021/4/1
Y1 - 2021/4/1
N2 - Background: In childhood immune thrombocytopenia (ITP), an autoimmune bleeding disorder, there is a need for better prediction of individual disease courses and treatment outcomes. Objective: To predict the response to intravenous immunoglobulins (IVIg) and ITP disease course using genetic and immune markers. Methods: Children aged younger than 7 years with newly diagnosed ITP (N = 147) from the Treatment With or Without IVIG for Kids with ITP study were included, which randomized children to an IVIg or observation group. A total of 46 variables were available: clinical characteristics, targeted genotyping, lymphocyte immune phenotyping, and platelet autoantibodies. Results: In the treatment arm, 48/80 children (60%) showed a complete response (platelets ≥100 × 109/L) that lasted for at least 1 month (complete sustained response [CSR]) and 32 exhibited no or a temporary response (absence of a sustained response [ASR]). For a biological risk score, five variables were selected by regularized logistic regression that predicted ASR vs CSR: (1) hemoglobin; (2) platelet count; (3) genetic polymorphisms of Fc-receptor (FcγR) IIc; (4) the presence of immunoglobulin G (IgG) anti-platelet antibodies; and (5) preceding vaccination. The ASR sensitivity was 0.91 (95% confidence interval, 0.80-1.00) and specificity was 0.67 (95% confidence interval, 0.53-0.80). In the 67 patients of the observation arm, this biological score was also associated with recovery during 1 year of follow-up. The addition of the biological score to a predefined clinical score further improved the discrimination of favorable ITP disease courses. Conclusions: The prediction of disease courses and IVIg treatment responses in ITP is improved by using both clinical and biological stratification.
AB - Background: In childhood immune thrombocytopenia (ITP), an autoimmune bleeding disorder, there is a need for better prediction of individual disease courses and treatment outcomes. Objective: To predict the response to intravenous immunoglobulins (IVIg) and ITP disease course using genetic and immune markers. Methods: Children aged younger than 7 years with newly diagnosed ITP (N = 147) from the Treatment With or Without IVIG for Kids with ITP study were included, which randomized children to an IVIg or observation group. A total of 46 variables were available: clinical characteristics, targeted genotyping, lymphocyte immune phenotyping, and platelet autoantibodies. Results: In the treatment arm, 48/80 children (60%) showed a complete response (platelets ≥100 × 109/L) that lasted for at least 1 month (complete sustained response [CSR]) and 32 exhibited no or a temporary response (absence of a sustained response [ASR]). For a biological risk score, five variables were selected by regularized logistic regression that predicted ASR vs CSR: (1) hemoglobin; (2) platelet count; (3) genetic polymorphisms of Fc-receptor (FcγR) IIc; (4) the presence of immunoglobulin G (IgG) anti-platelet antibodies; and (5) preceding vaccination. The ASR sensitivity was 0.91 (95% confidence interval, 0.80-1.00) and specificity was 0.67 (95% confidence interval, 0.53-0.80). In the 67 patients of the observation arm, this biological score was also associated with recovery during 1 year of follow-up. The addition of the biological score to a predefined clinical score further improved the discrimination of favorable ITP disease courses. Conclusions: The prediction of disease courses and IVIg treatment responses in ITP is improved by using both clinical and biological stratification.
KW - immune thrombocytopenia
KW - intravenous immunoglobulins
KW - molecular epidemiology
KW - pediatrics
KW - prognosis
UR - http://www.scopus.com/inward/record.url?scp=85102643329&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/jth.15232
DO - https://doi.org/10.1111/jth.15232
M3 - Article
C2 - 33386662
SN - 1538-7933
VL - 19
SP - 1071
EP - 1081
JO - Journal of thrombosis and haemostasis
JF - Journal of thrombosis and haemostasis
IS - 4
ER -