Abstract Number: PB1346
Meeting: ISTH 2020 Congress
Background: High dose corticosteroids are the recommended first line treatment for adults with ITP, but side effects are common and responses heterogeneous with about 20-30% not responding at tolerable doses. However, currently, there is no way to predict response pre-treatment.
We previously demonstrated that CD4+ T Cells from refractory ITP patients expressed a lower ratio of IL10:IL17 when treated ex vivo with glucocorticoids compared to responders (Blood (2017):130(Supplement 1);2312).
Aims: To prospectively validate this finding in a cohort of newly diagnosed ITP patients receiving first line corticosteroids.
Methods: Patients with ITP recruited to the FLIGHT multicentre RCT (ISRCTN95606674) were offered inclusion into the laboratory sub-study. Following consent, peripheral blood was taken at randomisation. Here we present data from patients randomised to the corticosteroid only group (not receiving IVIG within 2 weeks of treatment initiation). CD4+ T cells were isolated and examined by multiparameter flow cytometry pre-culture, and after 96h culture with activation via the T cell receptor +/- dexamethasone. After 2 weeks of corticosteroid, clinical response was classified as complete response(CR):pl >100×109/L, partial response(PR):pl30-100 x109/L and no response(NR):pl< 30 x109/L.
Results: Blood samples were processed from 47 ITP patients in the first line corticosteroid only group who did not receive IVIG (27 male, 20 female, median age=57y, range 17-87y, 24CR, 10PR, 13NR).
CD4+ T cells from NR patients had reduced IL-10:IL-17 expression ratio than CR patients pre-culture (p=0.0069; Figure 1A) and when cultured/activated in the presence of dexamethasone (p=0.0359; Figure 1B). No significant changes were seen between response groups in the other cytokines examined (IL-4, IL-22, IFN-γ, TNF, GM-CSF).
Conclusions: These data support that CD4+ T cells are important mediators of clinical response to corticosteroid treatment, and the cytokine signature of CD4+ T cells may form the basis of a laboratory biomarker to help predict clinical response to corticosteroids for patients with ITP.
|Total (n=)||Male (n=)||Female (n=)||Median Age and range (years)|
[Table 1 Patient demographics]
To cite this abstract in AMA style:Stimpson M, Lait P, Schewitz-Bowers L, Williams E, Lee R, Bradbury C. CD4+ T Cell Expression of IL-10 Compared to IL-17 is Lower in Patients with Immune Thrombocytopenia (ITP) Who Do Not Respond Clinically to High Dose Corticosteroid [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/cd4-t-cell-expression-of-il-10-compared-to-il-17-is-lower-in-patients-with-immune-thrombocytopenia-itp-who-do-not-respond-clinically-to-high-dose-corticosteroid/. Accessed January 23, 2022.
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