RESUMEN
Objectives: Giant inclusions in leukocytes is a common feature that can be observed in some infections but can be also related to rare genetic disorders such as Chédiak-Higashi syndrome (CHS). A differential diagnosis between these groups of diseases has to be performed using specific genetic tests. Clinical and pathological history is relevant for a diagnostic orientation due to the difficulty and specificity of the diagnostic confirmation. Case presenation: We present the case of a 3-years-old male patient with recurrent respiratory infections. It is important to highlight the presence of a lock of white hair on the front of the head and some hypopigmentation of the skin. In the blood smear, the presence of big cytoplasm granules in all the leukocytes, especially in neutrophils. Conclusions: CHS is an uncommon genetic disorder caused by the mutation in the LYST gene situated in chromosome 1q42.3 which codified for LYST protein. Molecular genetic testing also can be done to detect the biallelic variants in the LYST gene. It is essential to perform peripheral blood smears in the presence of changes in quantitative and/or qualitative values in the complete blood count as a first step in the diagnosis algorithm.
RESUMEN
The intestine is vulnerable to chemotherapy-induced damage due to the high rate of intestinal epithelial cell (IEC) proliferation. We have developed a human intestinal organoid-based 3D model system to study the direct effect of chemotherapy-induced IEC damage on T cell behavior. Exposure of intestinal organoids to busulfan, fludarabine, and clofarabine induced damage-related responses affecting both the capacity to regenerate and transcriptional reprogramming. In ex vivo co-culture assays, prior intestinal organoid damage resulted in increased T cell activation, proliferation, and migration. We identified galectin-9 (Gal-9) as a key molecule released by damaged organoids. The use of anti-Gal-9 blocking antibodies or CRISPR/Cas9-mediated Gal-9 knock-out prevented intestinal organoid damage-induced T cell proliferation, interferon-gamma release, and migration. Increased levels of Gal-9 were found early after HSCT chemotherapeutic conditioning in the plasma of patients who later developed acute GVHD. Taken together, chemotherapy-induced intestinal damage can influence T cell behavior in a Gal-9-dependent manner which may provide novel strategies for therapeutic intervention.
