Increased SOX10, p16, and Cyclin D1 Immunoreactivity Differentiates MAP Kinase-activated Low-grade Gliomas From Piloid Gliosis.

Low-grade gliomas and reactive piloid gliosis can present with overlapping features on conventional histology. Given the large implications for patient treatment, there is a need for effective methods to discriminate these morphologically similar but clinically distinct entities. Using routinely available stains, we hypothesize that a limited panel including SOX10, p16, and cyclin D1 may be useful in differentiating mitogen-activated protein (MAP) kinase-activated low-grade gliomas from piloid gliosis.

Multiplatform molecular analyses refine classification of gliomas arising in patients with neurofibromatosis type 1.

Gliomas arising in the setting of neurofibromatosis type 1 (NF1) are heterogeneous, occurring from childhood through adulthood, can be histologically low-grade or high-grade, and follow an indolent or aggressive clinical course. Comprehensive profiling of genetic alterations beyond NF1 inactivation and epigenetic classification of these tumors remain limited. Through next-generation sequencing, copy number analysis, and DNA methylation profiling of gliomas from 47 NF1 patients, we identified 2 molecular subgroups of NF1-associated gliomas.

Targeted Next-Generation Sequencing Reveals Divergent Clonal Evolution in Components of Composite Pleomorphic Xanthoastrocytoma-Ganglioglioma.

Composite pleomorphic xanthoastrocytoma-ganglioglioma (PXA-GG) is an extremely rare central nervous system neoplasm with 2 distinct but intermingled components. Whether this tumor represents a "collision tumor" of separate neoplasms or a monoclonal neoplasm with divergent evolution is poorly understood. Clinicopathologic studies and capture-based next generation sequencing were performed on extracted DNA from all available PXA-GG at 2 medical centers.

Serologic markers of Epstein-Barr virus reactivation are associated with increased disease activity, inflammation, and interferon pathway activation in patients with systemic lupus erythematosus.

SLE is a clinically heterogeneous disease characterized by an unpredictable relapsing-remitting disease course. Although the etiology and mechanisms of SLE flares remain elusive, Epstein-Barr virus (EBV) reactivation is implicated in SLE pathogenesis. This study examined the relationships between serological measures of EBV reactivation, disease activity, and interferon (IFN)-associated immune pathways in SLE patients.

COVID-19 Pandemic Spurs Evolution of an Academic Pathology Department and Laboratory.

The COVID-19 pandemic has caused much suffering through disease and death, disruption of daily life, and economic havoc. Global health infrastructure has been challenged, in some cases failing. In the United States, the inability of laboratories to provide adequate testing for the causative pathogen, severe acute respiratory syndrome coronavirus 2, has been the subject of negative press and national debate.

A case of invasive pulmonary mucormycosis resulting from short courses of corticosteroids in a well-controlled diabetic patient.

A patient with well-controlled type 2 diabetes mellitus developed a severe pulmonary infection secondary to spp. after receiving short courses of corticosteroids for a respiratory tract infection. He recovered after an aggressive surgical intervention and treatment with isavuconazole.

Autoantibody-positive healthy individuals with lower lupus risk display a unique immune endotype.

Background: Autoimmune diseases comprise a spectrum of illnesses and are on the rise worldwide. Although antinuclear antibodies (ANAs) are detected in many autoimmune diseases, up to 20% of healthy women are ANA-positive (ANA+) and most will never develop clinical symptoms. Furthermore, disease transition is higher among ANA+ African Americans compared with ANA+ European Americans.

Adults with systemic lupus exhibit distinct molecular phenotypes in a cross-sectional study.

Background: The clinical and pathologic diversity of systemic lupus erythematosus (SLE) hinders diagnosis, management, and treatment development. This study addresses heterogeneity in SLE through comprehensive molecular phenotyping and machine learning clustering.

Methods: Adult SLE patients ( = 198) provided plasma, serum, and RNA.

Author Correction: Immunologic findings precede rapid lupus flare after transient steroid therapy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Unique Sjögren's syndrome patient subsets defined by molecular features.

Objective: To address heterogeneity complicating primary SS (pSS) clinical trials, research and care by characterizing and clustering patients by their molecular phenotypes.

Methods: pSS patients met American-European Consensus Group classification criteria and had at least one systemic manifestation and stimulated salivary flow of ⩾0.1 ml/min.

Immunologic findings precede rapid lupus flare after transient steroid therapy.

Systemic lupus erythematosus (SLE) flares elicit progressive organ damage, leading to disability and early mortality. This study evaluated clinical and immunologic factors associated with impending flare in the Biomarkers of Lupus Disease study. Autoantibodies and 32 soluble mediators were measured by multiplex assays, immune pathway activation by gene expression module scores, and immune cell subset frequencies and activation states by flow cytometry.

Case of Neonatal Fatality from Neuromuscular Variant of Glycogen Storage Disease Type IV.

Glycogen storage disease type IV (GSD-IV), or Andersen disease, is a rare autosomal recessive disorder that results from the deficiency of glycogen branching enzyme (GBE). This in turn results in accumulation of abnormal glycogen molecules that have longer outer chains and fewer branch points. GSD-IV manifests in a wide spectrum, with variable phenotypes depending on the degree and type of tissues in which this abnormal glycogen accumulates.

Dysregulation of innate and adaptive serum mediators precedes systemic lupus erythematosus classification and improves prognostic accuracy of autoantibodies.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a poorly understood preclinical stage of immune dysregulation and symptom accrual. Accumulation of antinuclear autoantibody (ANA) specificities is a hallmark of impending clinical disease. Yet, many ANA-positive individuals remain healthy, suggesting that additional immune dysregulation underlies SLE pathogenesis.

Combined role of vitamin D status and CYP24A1 in the transition to systemic lupus erythematosus.

Objective: We examined whether measures of vitamin D were associated with transitioning to systemic lupus erythematosus (SLE) in individuals at risk for SLE.

Methods: 436 individuals who reported having a relative with SLE but who did not have SLE themselves were evaluated at baseline and again an average of 6.3 (±3.

Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification.

Objectives: The relationship of immune dysregulation and autoantibody production that may contribute to systemic lupus erythematosus (SLE) pathogenesis is unknown. This study evaluates the individual and combined contributions of autoantibodies, type I interferon (IFN-α) activity, and IFN-associated soluble mediators to disease development leading to SLE.

Methods: Serial serum specimens from 55 individuals collected prior to SLE classification (average timespan=4.

Autoantibody-Positive Healthy Individuals Display Unique Immune Profiles That May Regulate Autoimmunity.

Objective: Antinuclear antibodies (ANAs) are detected in ∼18% of females, yet autoimmune disease develops in only 5-8%. Immunologic differences between ANA-positive healthy individuals and patients with systemic lupus erythematosus (SLE) may elucidate the regulatory mechanisms by which ANA-positive individuals avoid transition to clinical autoimmune disease.

Methods: Healthy individuals (n = 790) were screened for autoantibodies specific for 11 antigens associated with lupus, systemic sclerosis, and Sjögren's syndrome.

Vitamin d deficiency in a multiethnic healthy control cohort and altered immune response in vitamin D deficient European-American healthy controls.

Objective: In recent years, vitamin D has been shown to possess a wide range of immunomodulatory effects. Although there is extensive amount of research on vitamin D, we lack a comprehensive understanding of the prevalence of vitamin D deficiency or the mechanism by which vitamin D regulates the human immune system. This study examined the prevalence and correlates of vitamin D deficiency and the relationship between vitamin D and the immune system in healthy individuals.

Two functional lupus-associated BLK promoter variants control cell-type- and developmental-stage-specific transcription.

Efforts to identify lupus-associated causal variants in the FAM167A/BLK locus on 8p21 are hampered by highly associated noncausal variants. In this report, we used a trans-population mapping and sequencing strategy to identify a common variant (rs922483) in the proximal BLK promoter and a tri-allelic variant (rs1382568) in the upstream alternative BLK promoter as putative causal variants for association with systemic lupus erythematosus. The risk allele (T) at rs922483 reduced proximal promoter activity and modulated alternative promoter usage.

Comparison of autoantibody specificities between traditional and bead-based assays in a large, diverse collection of patients with systemic lupus erythematosus and family members.

Objective: Replacement of standard immunofluorescence methods with bead-based assays for antinuclear antibody (ANA) testing is a new clinical option. The aim of this study was to evaluate a large, multiethnic cohort of patients with systemic lupus erythematosus (SLE), blood relatives, and unaffected control individuals for familial aggregation and subset clustering of autoantibodies by high-throughput serum screening technology and traditional methods.

Methods: Serum samples (1,540 SLE patients, 1,154 unaffected relatives, and 906 healthy, population-based controls) were analyzed for SLE autoantibodies using a bead-based assay, indirect immunofluorescence (IIF), and immunodiffusion.