Molecular Investigation of Iranian Patients Suspected to Hereditary Spherocytosis

Introduction: Hereditary spherocytosis is a heterogeneous disorder with mild to moderate anemia. The aim of this study was to evaluate the inherited spherocytosis gene mutations in patients with RBC cytoplasmic disorders in Iranian population. Materials and Methods: In this study, Whole Exome Sequencing (WES) was performed for patients suspected to hereditary spherocytosis and their relatives. Results: Sequence analysis of the probands and their parents identified variations in ANK1 gene (NM_001142446.1:c.127-2A>G), SPTB (c. 14delC, p.Thr5LysfsTer41), SPTA1 (c.466C>T), SLC4A1 (c.2494C>T) and SLC25A38 gene (c.683G>T, NP_060345.2:p.Gly228Val that could be related to the patients clinical manifestation. Conclusion: Findings are in line with the appropriate diagnostic yield of WES in determining the causative variant especially in those disorders that many genes are involved like anemia. This is the first report of a cohort of Iranian patients with anemia suspected to that were investigated using WES technology. Further studies are needed to investigate the distribution of gene mutations in patients with RBC membrane disorders in Iran

Soluble Mediators Potentially Involved in Pruritus Associated to Cutaneous T-Cell Lymphomas and Mastocytosis: A Cross-Sectional Study

Pruritus is a major distressing symptom, common in inflammatory diseases, like Cutaneous T-Cell Lymphoma (CTCL) and mastocytosis. We aimed to study the involvement of some molecules, namely, cytokines, neuromediators, endothelial adhesion molecules and angiogenic factors, in the severity of pruritus associated to CTCL and mastocytosis. CTCL - Mycosis Fungoides (MF, n=17) and Sézary syndrome (SS, n=10) and mastocytosis patients (n=17) were evaluated. Interleukin (IL)-8, IL-31, Vascular Endothelial Growth Factor (VEGF), E-selectin, serotonin and C-reactive protein (CRP) levels, were assessed; tryptase was measured in mastocytosis. Pruritus severity was assessed, using a Visual Analogue Scale (VAS). Compared to controls (n=29), CTCL patients presented higher CRP and IL-31. SS patients had higher IL-31, E-selectin and CRP than MF patients and controls. Itch correlated with IL- 31 and E-selectin, when considering all CTCL patients; in SS, itch correlated with E-selectin. Advanced CTCL stages revealed higher IL-31, E-selectin and CRP than early stages, and controls; itch intensity correlated with IL-31 and E-selectin, in advanced stages. Mastocytosis showed higher serotonin and VEGF, compared to controls, and itch intensity correlated with tryptase. Data suggest that in mastocytosis, serotonin is an important biomarker and that tryptase levels reflect itch intensity; IL-31 and E-selectin appear to be more important mediators in CTCL and strongly correlated with itch severity. The different involvement of studied mediators, probably due to different immune responses, suggests that different mechanisms underlie these diseases and may lead to different itch mechanisms.

Atypical Neurologic Complications Post Autologous Stem Cell Transplantation

We describe the case of a patient with high grade, triple hit, Non-Hodgkin’s Lymphoma (NHL) who underwent high-dose chemotherapy and Autologous Stem Cell Transplantation (ASCT) as a consolidation. Patient received BEAM conditioning regimen. She engrafted after usual post ASCT course. However, 2 months post ASCT she developed atypical neurologic symptoms and findings leading to general weakness mainly in the lower extremities with multiple falls, mental status changes and high CSF protein with severe sensorimotor neuropathy. She initially failed treatment with IVIg but responded to high dose steroids. More than one year after transplant, she has maintained her neurological improvement, but unable to walk, while her NHL continues to be in remission.