Novel ZAP-70-Related Immunodeficiency Presenting with Epstein–Barr Virus Lymphoproliferative Disorder and Hemophagocytic Lymphohistiocytosis

Zeta-chain-associated protein kinase 70 (ZAP-70) plays an integral role in the T-cell antigenic receptor complex. A deficiency of this kinase leads to a phenotype of severe combined immunodeficiency, while hypomorphic mutations of the kinase lead to more mild immunodeficiency phenotypes. We present a case of a 21-year-old patient with lymphadenopathy who was found to have Epstein–Barr virus (EBV) lymphoproliferative disease (LPD) and the development of hemophagocytic lymphohistiocytosis (HLH). On further workup, the patient was ultimately found to have a homozygous intrionic mutation in ZAP-70. This is a novel ZAP-70 mutation (c.1623 + 5G > A) associated with combined immunodeficiency and an EBV-positive LPD. A primary immunodeficiency is important to consider in a young, otherwise healthy patient presenting with an EBV-positive LPD.

Evaluation of interleukin-9 expression as a potential therapeutic target in chronic lymphocytic leukemia in a cohort of Egyptian patients

Background: Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy that has a highly variable clinical course. Genomic features as zeta-chain-associated protein kinase 70 (ZAP70) expression and CD38 expression provide further differentiation of disease prognosis. Extensive studies have confirmed the oncogenic activities of IL-9 in lymphoma. The aim of the current study was to investigate the contribution of IL-9 expression to the pathogenesis of CLL and its correlation to other prognostic parameters.Methods: This study was conducted on 80 patients at diagnosis with CLL and 80 healthy controls. Using real time polymerase chain reaction and enzyme linked immunosorbant assay, IL-9 mRNA expression and its serum level were compared between patients and controls. They were both correlated with other prognostic factors.Results: There was an overexpression of IL-9 in CLL patients that correlated with modified Rai staging, ZAP70, CD38 and all hallmarks of an active and aggressive disease. The correlation between IL-9 upregulation and patient characteristics provided a direct clinical evidence for its contribution to the pathogenesis of CLL.Conclusions: Significantly higher expression of IL -9 measured at both the mRNA and the protein levels in patients with CLL that correlates with more complex course of the disease and worse prognosis may allow one to speculate its importance in the pathogenesis of the disease and its possible role as a potential therapeutic target.

Physical evaluation, morphological and identification of seminal proteins in Santa Ines sheep

SUMMARY This study aimed to identify proteins in the seminal plasma associated with fertility in sheep of Santa Inês in Manaus, AM, using twodimensional electrophoresis techniques associated with mass spectrometry. Semen samples from eight adult sheep were collected by removing an aliquot for the physical and morphological assessments of semen and seminal plasma was subjected to SDS-PAGE profile and two-dimensional electrophoresis. Gels were stained with colloidal Coomassie, scanned and analyzed using ImageMaster 2D Platinum software, version 6.0. The selected individual spots were cut from the master gel, digested with trypsin and subjected to identification by mass spectrometry (MALDITof / Tof). Of the 108 spots detected in the gel, it selected 10 differential spots (based on the distribution thereof in the bidimensional gel and pre-analysis of the 2D ImageMaster Platinum Software) identifying 03 proteins: clusterin, a protein 14-3-3 zeta chain and Ram Seminal versicles 22kDa Protein. The identity of these proteins implies that the components of seminal plasma participate in physiological processes involved in sperm protection, motility and sperm capacitation, all associated with fertility. These proteins need to be better studied to see whether the same could be used as molecular markers of fertility as they were also found in other studies conducted with sheep Santa Ines.

Increased ZAP70 Is Involved in Dry Skin Pruritus in Aged Mice

Dry skin pruritus is common in the elderly. Recent reports show that T-cell signal path is involved in dry skin pruritus. Zeta-chain-associated protein kinase 70 (ZAP70), as a T-cell receptor, may induce interleukin 2 (IL-2) secretion and promote nerve growth factor (NGF) secretion in skin. This study aimed to detect the alteration of ZAP70 in a mice model with dry skin pruritus. The C57BL mice with 5 months and 22 months were used as experimental animal. Following a 5-day period of treatment of back with a mixture of acetone-diethyl-ether-water (AEW), mice exhibited a significant increase in spontaneous scratching behavior directed to the treated back compared to control animals in which back was similarly treated with water only (W). After AEW process, spontaneous scratching in 22-month AEW mice was increased compared to 5-month AEW mice. Western blot and real-time quantitative PCR data analysis showed that ZAP70 expression was significantly increased in 22-month AEW mice compared with 5-month AEW mice. ELISA data showed that secretions of IL-2 and NGF in 22-month AEW mice were higher than 5-month AEW mice. Our results indicate that increased ZAP70 is involved in dry skin in elderly pruritus. Increased secretion of IL-2 and NGF may induce dry skin itch.