Multiple GYPB gene deletions associated with the U- phenotype in those of African ancestry.

BACKGROUND: The MNS blood group system is defined by three homologous genes: GYPA, GYPB, and GYPE. GYPB encodes for glycophorin B (GPB) carrying S/s and the "universal" antigen U. RBCs of approximately 1% of individuals of African ancestry are U- due to absence of GPB. The U- phenotype has long been attributed to a deletion encompassing GYPB exons 2 to 5 and GYPE exon 1 (GYPB*01N). STUDY DESIGN AND METHODS: Samples from two U-individuals underwent Illumina short read whole genome sequencing (WGS) and Nanopore long read WGS. In addition, two existing WGS datasets, MedSeq (n = 110) and 1000 Genomes (1000G, n = 2535), were analyzed for GYPB deletions. Deletions were confirmed by Sanger sequencing. Twenty known U- donor samples were tested by a PCR assay to determine the specific deletion alleles present in African Americans. RESULTS: Two large GYPB deletions in U- samples of African ancestry were identified: a 110 kb deletion extending left of GYPB (DEL_B_LEFT) and a 103 kb deletion extending right (DEL_B_RIGHT). DEL_B_LEFT and DEL_B_RIGHT were the most common GYPB deletions in the 1000 Genomes Project 669 African genomes (allele frequencies 0.04 and 0.02). Seven additional deletions involving GYPB were seen in African, Admixed American, and South Asian samples. No samples analyzed had GYPB*01N. CONCLUSIONS: The U- phenotype in those of African ancestry is primarily associated with two different complete deletions of GYPB (with intact GYPE). Seven additional less common GYPB deletion backgrounds were found. GYPB*01N, long assumed to be the allele commonly encoding U- phenotypes, appears to be rare.

Use of Human Leukocyte Antigen (HLA)-Incompatible Platelet Units in HLA Platelet-Refractory Patients With Limited Number of or Low-Level HLA Donor-Specific Antibodies Results in Permissive Transfusions.

CONTEXT.­: In human leukocyte antigen (HLA)-mediated alloimmune platelet refractoriness, HLA-incompatible platelets may produce adequate posttransfusion corrected count increment ("permissive transfusion") and increase the donor pool. OBJECTIVE.­: To determine if a lower number of or low-level anti-HLA donor-specific antibodies (DSAs) predict permissive transfusion and could be used to prioritize platelet selection. DESIGN.­: We categorized platelets administered from 2016 to 2018 as HLA-compatible or HLA-incompatible based on presence of DSAs against the donor unit. We further divided HLA-incompatible units based on the number of DSAs and the level of DSAs (measured by mean fluorescence intensity [MFI]), where cumulative MFI ≥6000 defines high-level DSA. We compared posttransfusion corrected count increments (CCIs) and transfusion reactions among these transfusions. RESULTS.­: Of 279 HLA-selected units transfused into 26 platelet-refractory patients, we resorted to using 39 HLA-incompatible units (14%). Posttransfusion CCI and transfusion reaction frequency were similar among units targeted by 1 or low-level DSAs and HLA-compatible units. Units targeted by ≥2 distinct or high-level DSAs produced lower CCIs. Regardless of ABO compatibility, similarly HLA-categorized units yielded comparable CCIs and comparable frequency of transfusion reactions. CONCLUSIONS.­: HLA-incompatible platelets transfused across 1 or low-level DSAs were commonly permissive, whereas those transfused across ≥2 DSAs or high levels of DSA (MFI ≥6000) were nonpermissive. The use of such donor units offers transfusion services alternative platelet units for support of platelet-refractory patients.

Intracranial Dural Parafalcine Chondroma: Case Report and Systematic Review of the Literature.

Intracranial chondromas are rare, benign neoplasms representing only 0.2%-0.3% of neoplastic intracranial lesions. They commonly originate from the skull base but can infrequently arise from the falx, convexity dura, or ventricular ependyma. Diagnosis requires histopathologic confirmation, as patients present with nonspecific symptoms related to mass effect, and imaging characteristics often resemble meningiomas, oligodendrogliomas, and vascular malformations. We describe the case of a patient harboring a parafalcine dural chondroma that was discovered incidentally and was managed surgically at our institution. We also provide a systematic review of the literature to elucidate incidence, origin, imaging findings, surgical management approaches, and prognosis of this rare tumor.

Linagliptin unmasks specific antioxidant pathways protective against albuminuria and kidney hypertrophy in a mouse model of diabetes.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects on diabetic kidney disease (DKD) via specific antioxidant pathways. The DPP-4 inhibitor, linagliptin, was evaluated with the hypothesis that DPP-4 inhibition would ameliorate the development of DKD in a glucose-independent manner by altering specific antioxidant function. METHODS: DBA/2J mice (a well-characterized model of DKD) and glucose 6-phosphate dehydrogenase (G6PD) deficient mice (a model of impaired antioxidant function) were evaluated. Diabetes was induced by streptozotocin. Mice were divided into: diabetic (DM), diabetic+linagliptin (DM+Lina), and non-diabetic control and treated for 12 weeks. RESULTS: In DBA/2J mice, there was no difference in body weight and blood glucose between DM and DM+Lina groups. Linagliptin ameliorated albuminuria and kidney hypertrophy in DM DBA/2J mice and specifically increased the mRNA and protein levels for the antioxidants catalase and MnSOD. In G6PD deficient mice, however, increases in these mRNA levels did not occur and linagliptin renoprotection was not observed. Linagliptin also ameliorated histological trends toward mesangial expansion in wild-type mice but not in G6PD deficient mice. CONCLUSIONS: Linagliptin renoprotection involved glucose-independent but antioxidant-enzyme-system-dependent increases in transcription (not just increased protein levels) of antioxidant proteins in wild-type mice. These studies demonstrate that an intact antioxidant system, in particular including transcription of catalase and MnSOD, is required for the renoprotective effects of linagliptin.