Integrative Diagnosis for SCD and Other RADs

Primary objective

INTEGRA aims at enabling personalized medicine for RADs patients by the establishment of an integrative diagnostic approach based on deep phenotypic and genetic characterization through combining new generation methodologies.

Secondary objectives

• To assess the prognostic value of the newly invented Lorrca® oxygenscan ektacytometer as biomarker providing information of SCD patients severity and response to treatment.
• To investigate the correlation between Lorrca® parameters and RAD patients genetic and phenotypic characterization.
• To identify genetic modifiers of RADs both new and previously described as markers for prognosis and clinical course based on genomics approach.
• To model the progression of RADs in a spleen-like filtering unit using microfluidic technologies to develop a novel diagnostic device for prognosis and patients' stratification. This device will be used for the characterization under flow of rheological and mechanical properties of single RBCs.
• To establish an innovative algorithm for RADs patient's characterization based on the integration of data generated through the analysis of genetic modifiers and the RBCs rheological/mechanical properties by Lorrca® profiles and microfluidics data in combination with RADs patients' clinical manifestations and treatments.
• To translate the results on a clinical practice recommendation for management of RADs patients endorsed by European Hematology bodies as ERN-EuroBloodNet and/or the European Hematology Association for its wide dissemination.
• To disseminate the results obtained among the main target groups: pediatricians, hematologists, public health authorities, and patients' community.

Genetic modifiers for rare anemia disorders will be analyzed through massive sequencing.

Peripheral blood samples will be used for conventional phenotyping characterization including among others: RBCs morphology, fragility osmotic test, hemoglobin fraction and quantification, hemoglobin stability test, EMA binding test, RBC enzymes quantification assay, RBC rheological properties through Lorrca Maxsis Osmoscan/Oxygescan (Lorrca®)

Time frame: Through study completion, an average of 2 years

Severity was assesed as the occurence of:

• Vaso-occlusive events (VOEs) in the last 24 months
• Kidney injury (defined according to KDIGO guidelines)
• Retinopathy (defined as proliferative and non proliferative)

Time frame: Through study completion, an average of 2 year

Genomic data will be generated using a targeted next-generation sequencing (tNGS) approach.

Means, medians, standard deviations (SD), ranges and percentages were calculated using SPSS software (version 20, IBM SPSS Statistics, Chicago, IL, USA). Spearman's rank correlation was used to assess associations between variables. For comparing variables with two categories, either a student's t-test or a Mann-Whitney U test was performed, when appropriate. When the variable had more than two categories, an ANOVA or Kruskal Wallis test was used. A p value \<0.05 was considered statistically significant.

Integrative Diagnosis of Sickle Cell Disease (SCD) and Other Rare Anemia Disorders (RADs) for Personalized Medicine