Mayo Clinic Laboratory and Pathology Research Roundup: June 29
The research roundup provides an overview of the past week’s research from Mayo Clinic Laboratories consultants, including featured abstracts and a complete list of published studies and reviews.
Neuromyelitis optica (NMO) is a severe inflammatory autoimmune CNS disorder triggered by binding of an IgG autoantibody to the aquaporin 4 (AQP4) water channel on astrocytes. Activation of cytolytic complement has been implicated as the major effector of tissue destruction that secondarily involves myelin. We investigated early precytolytic events in the evolving pathophysiology of NMO in mice by continuously infusing IgG (NMO patient serum-derived or AQP4-specific mouse monoclonal), without exogenous complement, into the spinal subarachnoid space. Motor impairment and sublytic NMO-compatible immunopathology were IgG dose dependent, AQP4 dependent, and, unexpectedly, microglia dependent. In vivo spinal cord imaging revealed a striking physical interaction between microglia and astrocytes that required signaling from astrocytes by the C3a fragment of their upregulated complement C3 protein. Astrocytes remained viable but lost AQP4. Previously unappreciated crosstalk between astrocytes and microglia involving early-activated CNS-intrinsic complement components and microglial C3a receptor signaling appears to be a critical driver of the precytolytic phase in the evolving NMO lesion, including initial motor impairment. Our results indicate that microglia merit consideration as a potential target for NMO therapeutic intervention. Via The Journal of Clinical Investigation.
Published to PubMed This Week
- Accurate Nonendoscopic Detection of Barrett's Esophagus by Methylated DNA Markers: A Multisite Case Control Study.
American Journal of Gastroenterology
- Development and Validation of the Gene-Expression Predictor of high-Grade-Serous Ovarian Carcinoma Molecular subTYPE (PrOTYPE).
Clinical Cancer Research
- Subtypes of Dementia with Lewy Bodies are Associated with A-Synuclein and Tau Distribution.
- Steroid-Sparing Maintenance Immunotherapy for MOG-IgG Associated Disorder.
- Molecular and Direct Detection Tests for Treponema pallidum Subspecies pallidum: A Review of the Literature, 1964-2017.
Clinical Infectious Disease
- A Framework for Evidence Synthesis Programs to Respond to a Pandemic.
Mayo Clinic Proceedings
- Utilizing Multiparametric Flow Cytometry in the Diagnosis of Patients with Primary Plasma Cell Leukemia.
American Journal of Hematology
- Aetiology and Outcomes of Secondary Myelofibrosis Occurring in the Context of Inherited Platelet Disorders: A Single Institutional Study of Four Patients.
British Journal of Haematology
- Responding to the Challenges of SARS-CoV-2: Perspectives from the Association for Molecular Pathology (AMP) Infectious Disease Subdivision Leadership.
Journal of Molecular Diagnostics
- Assessment of Clinical Outcomes with Immune Checkpoint Inhibitor Therapy in Melanoma Patients with CDKN2A and TP53 Pathogenic Mutations.
- Correlation of Novel ALKATI with ALK Immunohistochemistry and Clinical Outcomes in Metastatic Melanoma.
- Factors Predicting Early Mortality After Radical Cystectomy for Urothelial Carcinoma in a Contemporary Cohort of Patients.
Cancer Urology Association Journal
- Population-based Assessment of Aortic-related Outcomes in Aortic Dissection, Intramural Hematoma, and Penetrating Aortic Ulcer.
Annals of Vascular Surgery
- Outcomes of Pregnancy in Operative vs. Nonoperative Adolescent Idiopathic Scoliosis Patients at Mean 30-Year Follow-up.
- Effect of Alteplase Administration on International Normalized Ratio in Patients With Acute Ischemic Stroke.