Novel Inherited N-terminus TAP1 Variants and Severe Clinical Manifestations- Are Genotype-Phenotype Correlations Emerging?

Major histocompatibility complex class I deficiency results from deleterious biallelic variants in TAP1, TAP2, TAPBP, and B2M genes. Only a few patients with variant-curated TAP1 deficiency (TAP1D) have been reported in the literature and the clinical phenotype has been variable with an emphasis on autoimmune and inflammatory complications. We report TAP1D in a Nepalese girl with a severe clinical phenotype with serious viral infections at a very young age.

Small molecule APOL1 inhibitors as a precision medicine approach for APOL1-mediated kidney disease.

Chronic kidney disease affects ~10% of people worldwide and there are no disease modifying therapeutics that address the underlying cause of any form of kidney disease. Genome wide association studies have identified the G1 and G2 variants in the apolipoprotein L1 (APOL1) gene as major contributors to a subtype of proteinuric kidney disease now referred to as APOL1-mediated kidney disease (AMKD). We hypothesized that inhibition of APOL1 could have therapeutic potential for this genetically-defined form of kidney disease.

JAK inhibition decreases the autoimmune burden in Down syndrome.

Background: Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmunity and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined.

Methods: We report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS, including autoantibody profiling, cytokine analysis, and deep immune mapping.

Using Serum Metabolomic Signatures to Investigate Effects of Acupuncture on Pain-Fatigue-Sleep Disturbance in Breast Cancer Survivors.

Background/objectives: Acupuncture is an efficacious integrative therapy for treating pain, fatigue, and sleep disturbance (the psychoneurological symptom cluster) in breast cancer survivors. However, the mechanisms underlying its effects remain unclear, and related metabolomics studies are limited. This study aimed to examine serum metabolite changes after acupuncture and their relationships to symptom improvement.