Immunologic thrombocytopenic purpura (ITP) in children is a pre-lupus condition if associated with the presence of anti-nuclear antibodies (ANA), providing a unique model for understanding the natural history of autoimmunity, particularly that of systemic lupus erythematosus (SLE). The investigators will describe the shared and/or unique immunological pathways involved at diagnosis in 70 children with ITP and in 20 children with SLE, and compare them between ITP-ANA- (more often transient), ITP-ANA+ (pre-lupus condition, more often persistent) and SLE
Child or adolescent with newly diagnosed ITP or SLE according to the specific definitions of ITP or SLE, prior to any treatment,
Over 1 and under 18 years of age at diagnosis, weighing more than 7 kg.
Written consent from parents or guardians,
Patient affiliated to a social security scheme.
ITP secondary to a known cause: previous or concomitant immune deficiency, bone marrow or organ transplantation, other autoimmune disease, Evans syndrome (autoimmune hemolytic anemia or autoimmune neutropenia present at ITP diagnosis) or cancer with immunosuppressive therapy.
Treatment with immunomodulation or immunosuppressants (including immunoglobulins, corticoids, hydroxychloroquine), started prior to inclusion (day of sampling).
Pregnant women, women in labour and breastfeeding women
Suffering from an immunological disease,
Parallel
Blood sampling baseline and M3
Procedure/SurgeryBlood sampling is a routine biological procedure performed under the same conditions as during a follow-up consultation.
Monitoring for SLE
Other interventionMonitoring for Systemic Lupus Erythematosus according to SLICC 2012 classification criteria
Procedure/Surgery: Blood sampling baseline and M3 then each 6 months until 48 months
Procedure/SurgeryBlood sampling is a routine biological procedure performed under the same conditions as during a follow-up consultation.
moniktoring for SLE : baseline and M3 then each 6 months until 48 months
Other interventionMonitoring for Systemic Lupus Erythematosus according to SLICC 2012 classification criteria
Characterisation of B and T lymphocyte populations
Characterisation of B and T lymphocyte populations through the study of surface markers and intracellular factors. This panel will, in particular, enable the identification of effector B cells such as plasma blasts, subsets of auto-reactive 'double-negative' (DN) B cells, regulatory B cells, and follicular T helper (Tfh) and peripheral extra-follicular T helper (Tph) cells. Each population will be compared between the patients and the control group.
Plasma markers
Soluble cytokines and factors regulating B-cell survival (BAFF, TACI, IL-6, IL-12p70, IFN-γ, IFN-β, TGF-β, and the IFN-regulated chemokine CXCL10) will be quantified in plasma using a customised multiplex Luminex assay. Interferon alpha levels will be specifically measured using ultra-sensitive SIMOA (Single Molecule Array) technology.
Plasma markers
Circulating plasma autoantigens - soluble P-selectin and CD40L derived from platelet activation - will be measured by ELISA. The levels of circulating and mitochondrial DNA will be measured by quantitative RT-PCR in collaboration with V. Sisirak (DR CNRS, Immunoconcept). The overall activity of plasma DNases will be determined by an in vitro DNA degradation assay.
Single-cell transcriptomic analysis
Using single-cell RNA sequencing, a single-cell transcriptomic analysis, we will be able to quantify and analyse the transcriptomes of lymphocytes B This will enable us to characterise heterogeneous cell populations, as well as to reconstruct cell development pathways and model transcriptomic dynamics. This technique will enable the modelling of signalling pathways involving B lymphocytes in the subgroup of ITP patients with positive AAN titres, and the development of an algorithm and a mathematical model of the progression of these cellular and molecular markers
Single cell epigenetic analysis
Using single-cell ATAC sequencing, we will be able to analyse the regions of DNA accessible to the transcription machinery. This will enable us to identify regulatory programmes such as signalling pathways. The analysis will also reveal heterogeneity amongst B-cell subpopulations, which may respond differently to signals. This will provide insight into the epigenetic status of genes, or at least into which factors regulate this signalling pathway and how the cell adjusts its response depending on its situation or stage of maturity, or on the signal itself.
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