Pathology

Pathology is the medical discipline that elucidates disease processes by examining structural, biochemical and molecular alterations in cells, tissues and organs. It spans mechanisms of cell injury, inflammation, repair, neoplasia and host defence, integrating gross autopsy findings with microscopic, immunohistochemical, genetic and molecular techniques. As the cornerstone of diagnosis, patient stratification and therapeutic guidance, pathology informs clinical practice across specialties from nephrology to neurology. Recent technological advances—digital histology, high-resolution imaging modalities, ultrasensitive protein-aggregation assays and single-cell profiling—are driving a deeper understanding of disease heterogeneity and enabling precision interventions. Armed with this knowledge, pathologists not only confirm diagnoses but also uncover pathogenetic pathways, identify prognostic biomarkers and support the development of targeted therapies that improve patient outcomes.

Research from Nature Portfolio

In autoimmune kidney disease, emerging evidence has pinpointed the classical complement pathway as the principal driver of tissue injury. High-resolution studies of patient biopsies reveal co-localisation of C1q with deposited IgG, and experimental gene-silencing of complement component C3 markedly reduces proteinuria and preserves podocyte structure, suggesting complement inhibition as a promising therapeutic strategy. In neurodegenerative prion disorders, oligodendrocyte-lineage (NG2) glia have been shown to moderate microglial prostaglandin E2 production, protecting neurons from prion-induced toxicity; blockade of prostaglandin biosynthesis in organotypic cultures extends neuronal survival and slows disease progression in murine models. At the molecular level, cryo-electron microscopy of ex vivo prion fibrils has delineated parallel in-register β-sheet architectures and identified strain-specific folding subdomains; these structural insights explain intra-species strain diversity and could inform future approaches to diagnostic conformer discrimination.

Research from all publishers

Ultrasensitive protein-seeding assays have revolutionised prion quantitation by achieving sensitivity comparable to traditional animal bioassays. Combining quaking-induced conversion with end-point dilution analysis, investigators can now estimate prion seeding doses in days rather than months, enabling high-throughput assessment of infectivity in tissues and fluids. Beyond infectious agents, environmental factors are also implicated in barrier dysfunction: components of dishwasher rinse aids, notably alcohol ethoxylates, have been shown to disrupt intestinal epithelial tight junctions in vitro, reduce transepithelial resistance and trigger inflammatory gene programmes. These findings link everyday chemical exposures to barrier leakiness and chronic gut inflammation, highlighting a pathophysiological axis relevant to both gastrointestinal and systemic diseases.

Pathology publication trend

The graph below shows the total number of articles in pathology across all publications each year (not limited to Nature Index journals).

Technical terms

Podocyte: A specialised epithelial cell in the kidney glomerulus essential for filtration barrier integrity.

Complement system: A cascade of plasma proteins that, when activated via classical, lectin or alternative pathways, mediates inflammation and cell lysis.

NG2 glia: A lineage of oligodendrocyte-precursor cells involved in myelination and neuroinflammatory regulation.

Cryo-EM: Cryogenic electron microscopy, a technique for imaging biomolecular structures at near-atomic resolution in a frozen-hydrated state.

Prion seeding assay (QuIC): An ultrasensitive method exploiting misfolded prion protein’s ability to template conversion of recombinant PrP into detectable amyloid fibrils.

Tight junction: A multiprotein complex at the apical region of epithelial cells that seals neighbouring cells and regulates paracellular permeability.

Transepithelial electrical resistance: A measure of ionic conductance across an epithelial monolayer reflecting barrier integrity.

References

1. The classical pathway triggers pathogenic complement activation in membranous nephropathy. Nature Communications (2023).
2. NG2 glia protect against prion neurotoxicity by inhibiting microglia-to-neuron prostaglandin E2 signaling. Nature Neuroscience (2024).
3. A structural basis for prion strain diversity. Nature Chemical Biology (2023).
4. Rapid End-Point Quantitation of Prion Seeding Activity with Sensitivity Comparable to Bioassays. PLOS Pathogens (2010).
5. Gut epithelial barrier damage caused by dishwasher detergents and rinse aids. Journal of Allergy and Clinical Immunology (2022).
6. Basic Pathology.