Erythrocytes lacking the Langereis blood group protein ABCB6 are resistant to the malaria parasite Plasmodium falciparum.

The ATP-binding cassette transporter ABCB6 was recently discovered to encode the Langereis (Lan) blood group antigen. Lan null individuals are asymptomatic, and the function of ABCB6 in mature erythrocytes is not understood. Here, we assessed ABCB6 as a host factor for Plasmodium falciparum malaria parasites during erythrocyte invasion. We show that Lan null erythrocytes are highly resistant to invasion by P. falciparum, in a strain-transcendent manner. Although both Lan null and Jr(a-) erythrocytes harbor excess porphyrin, only Lan null erythrocytes exhibit a P. falciparum invasion defect. Further, the zoonotic parasite P. knowlesi invades Lan null and control cells with similar efficiency, suggesting that ABCB6 may mediate P. falciparum invasion through species-specific molecular interactions. Using tandem mass tag-based proteomics, we find that the only consistent difference in membrane proteins between Lan null and control cells is absence of ABCB6. Our results demonstrate that a newly identified naturally occurring blood group variant is associated with resistance to Plasmodium falciparum.

A case report of B lymphoblastic lymphoma with brain metastases: Clinical and pathological significance of head trauma misdiagnosis.

INTRODUCTION: B lymphoblastic lymphoma (B-LBL) is a rare type of lymphoma that originates from precursor lymphocytes. B-BLB in adults with brain metastases is extremely rare as the disease mainly affects children and adults. Therefore, such a seldom-seen case can easily trigger a dispute regarding clinical diagnosis and treatment.This paper reports the case of a 22-year-old man hospitalized for a head injury that resulted from a physical altercation. Upon admission to the hospital, the patient was diagnosed with a diffuse axonal injury (DAI). Accordingly, the patient receiving follow-up treatments, but died 30 days later. After a systematic necropsy, immunohistochemical staining, radiological consultation, and a complete review of the clinical dates, we defined the case as a brain metastasis of B lymphoblastic lymphoma. Imaging results of the intracranial lymphoma were nearly indistinguishable from DAI during the acute phase, which led to misdiagnosis and incorrect treatment for B-LBL. CONCLUSION: We present this case to broaden the scope of pathologic and clinical diagnosis for intracranial tumors and to inform physicians, general neurologists, and even medical examiners with an added degree of differential awareness in dealing with the clinical materials before further diacrisis and disposal.

CRISPR/Cas9 knockouts reveal genetic interaction between strain-transcendent erythrocyte determinants of Plasmodium falciparum invasion.

During malaria blood-stage infections, Plasmodium parasites interact with the RBC surface to enable invasion followed by intracellular proliferation. Critical factors involved in invasion have been identified using biochemical and genetic approaches including specific knockdowns of genes of interest from primary CD34+ hematopoietic stem cells (cRBCs). Here we report the development of a robust in vitro culture system to produce RBCs that allow the generation of gene knockouts via CRISPR/Cas9 using the immortal JK-1 erythroleukemia line. JK-1 cells spontaneously differentiate, generating cells at different stages of erythropoiesis, including terminally differentiated nucleated RBCs that we term "jkRBCs." A screen of small-molecule epigenetic regulators identified several bromodomain-specific inhibitors that promote differentiation and enable production of synchronous populations of jkRBCs. Global surface proteomic profiling revealed that jkRBCs express all known Pfalciparum host receptors in a similar fashion to cRBCs and that multiple Pfalciparum strains invade jkRBCs at comparable levels to cRBCs and RBCs. Using CRISPR/Cas9, we deleted two host factors, basigin (BSG) and CD44, for which no natural nulls exist. BSG interacts with the parasite ligand Rh5, a prominent vaccine candidate. A BSG knockout was completely refractory to parasite invasion in a strain-transcendent manner, confirming the essential role for BSG during invasion. CD44 was recently identified in an RNAi screen of blood group genes as a host factor for invasion, and we show that CD44 knockout results in strain-transcendent reduction in invasion. Furthermore, we demonstrate a functional interaction between these two determinants in mediating Pfalciparum erythrocyte invasion.