IL‐10 and IL‐17 expression by CD4+ T cells is altered in corticosteroid refractory immune thrombocytopenia (ITP)

Abstract

Background: Corticosteroids remain the first-line treatment for patients with immune thrombocytopenia (ITP). However, 20% to 30% of patients do not respond to treatment at tolerable doses. This variation in corticosteroid efficacy is replicated in other autoimmune diseases and may have an adaptive immune basis. Objective: To test the hypothesis that CD4 + T-cell responses to corticosteroids are different in patients with clinically defined corticosteroid refractory ITP. Methods: In this prospective cohort study, CD4 + T cells from patients with ITP were cultured in the presence or absence of dexamethasone (Dex). Intracellular cytokine expression was then quantified by flow cytometry and compared with patients' clinical response to corticosteroid treatment. A control cohort of patients with autoimmune uveitis was also studied to evaluate whether our findings were limited to ITP or are potentially generalizable across autoimmune diseases. Results: The ratio of interleukin (IL)-10 to IL-17 expression following CD4 + T cell culture with Dex was able to discriminate between ITP patients with a clinically defined complete (n = 33), partial (n = 12) or nonresponse (n = 11) to corticosteroid treatment (P = .002). These findings were replicated in patients with autoimmune uveitis (complete response n = 14, nonresponse n = 22; P = .01). Conclusions: There is a relative abrogation of IL-10 and persistence of IL-17 expression in the CD4 + T cells of patients who clinically fail corticosteroid therapy. This observation has potential to inform both our mechanistic understanding of the action of corticosteroids in the treatment of ITP, and as a biomarker for steroid refractory disease, with potential application across a range of hematological and nonhematological conditions.

CD4+ T cells from patients with glucocorticoid‐refractory immune thrombocytopenia have altered cytokine expression

“…5,6 It may be possible to develop the observed ex vivo T cell phenotype into a clinically applicable biomarker to help predict NR patients, which could then inform the clinical decision to initiate alternative therapy early. Our data may also be applicable to other autoimmune illnesses treated with glucocorticoids 8 and highlight the potential importance of CD4 + T cells in both ITP pathogenesis and therapy.…”

“…This is consistent with our previous findings. 8 There were no significant differences in the expression of interleukin (IL)-4, IL-22, interferon (IFN)-c, granulocyte-macrophage colonystimulating factor (GM-CSF) or tumour necrosis factor (TNF) between R and NR patients.…”

Mycophenolate Mofetil for First-Line Treatment of Immune Thrombocytopenia

“…For example, MMF could be used in a subset of patients expected to fail a glucocorticoid alone based on laboratory or clinical features . 36 Early use of MMF may also be particularly valuable for patients in whom early disease control with avoidance of relapse is a priority, either from the patient's perspective or on clinical grounds such as severe bleeding or 0 (0%) 0 (0%) * and 2 fold higher than baseline, ^data cannot be compared using statistical significance due to bias caused by excluding those who started second line therapy before going into remission as they don't have a median time we can use in this analysis although their time would have been longer.…”

Association of metformin treatment and outcome in adult patients with ITP and pre‐existing T2DM

“…3,4 However, approximately one-third of patients with ITP are resistant to corticosteroid therapy. 5 For these individuals, second-line treatments, including recombinant human thrombopoietin (rhTPO), thrombopoietin receptor agonists, rituximab, splenectomy and other methods have been employed. [6][7][8] Recently, decitabine has been shown to be an efficient and safe treatment for refractory ITP and has thus been recommended as a viable therapy for patients with ITP in China.…”