Immunological complexity of lupus across diverse populations: Pathogenesis, biomarkers, and translational gaps

Systemic lupus erythematosus (SLE) is an archetypal autoimmune disorder characterized by disrupted immune tolerance, abnormal type I interferon signaling, dysregulated B and T cell responses, complement activation, and the production of pathogenic autoantibodies. Despite major progress in elucidating its molecular and genetic basis, the immunological mechanisms driving SLE’s marked clinical heterogeneity across genetically and geographically diverse populations remain incompletely understood.A particularly underexplored dimension of SLE immunobiology lies in populations from Africa and other low-resource regions, where the disease develops in settings of distinct immunogenetic backgrounds and high infectious disease burdens, including endemic parasitic infections such as filariasis, malaria, and helminthiases. These exposures shape immune pathways by altering Th1/Th2/Th17 polarization, modulating autoantibody repertoires, and influencing regulatory T cell functions. Understanding how chronic infectious exposure intersects with autoimmune susceptibility offers a unique lens into SLE pathogenesis and immune regulation.In addition, immunological biomarkers and serological assays established in high-resource settings may exhibit different performance or accessibility in populations with distinct immune histories. This contributes to diagnostic gaps and therapeutic inequities, not as a public health issue but as a translational immunology challenge — highlighting the need for immunological tools calibrated to global diversity.This Research Topic aims to advance understanding of SLE immunopathogenesis across the full spectrum of genetic and environmental variation, while emphasizing mechanistic, translational, and population immunology. By integrating immunogenetic diversity, co-infection biology, and immune signaling, this collection seeks to reveal how genetic risk factors, infectious exposures, and immunoregulatory networks influence SLE onset, course, and treatment response. A central goal is to adapt immunological discoveries — biomarkers, immune profiling technologies, and targeted therapies — to settings that reflect real-world variability in immune system function.Particular emphasis will be placed on studies exploring how parasitic co-infections and other endemic pathogens influence autoimmune activation and tolerance mechanisms. These interactions provide a natural model for decoding the modulatory balance between immune activation and suppression, offering clues for novel therapeutic strategies. Likewise, research on immunogenetic variability, population-level immune responses, and translational applications of biomarker science will collectively illuminate the full immunological complexity of lupus.To gather insights across this spectrum, we welcome submissions that clearly address immunological mechanisms, whether fundamental or translational, and that align with the following themes:o Immunopathogenic mechanisms of SLE: type I interferon pathway, B and T cell dysregulation, complement, and neutrophil biologyo Immunogenetic diversity and ancestry-specific susceptibility to SLE, with focus on African and other understudied populationso Interactions between parasitic or endemic infections and autoimmune responses in SLE: molecular mechanisms and clinical consequenceso Impact of infectious co-morbidities on autoantibody profiles, immune phenotypes, and disease activityo Biomarker discovery and validation across diverse populations: adaptability and performance in low-resource settingso Immune profiling and immunophenotyping across genetically distinct SLE cohortso Advances in targeted immunotherapy and barriers to equitable access to immunomodulatory interventionso Translational approaches connecting laboratory immunology to clinical management in diverse environmentso Experimental and computational models reflecting global variation in genetic and infectious backgroundsAll submissions must present a clear immunological focus — mechanistic, translational, or biomarker-driven. Manuscripts addressing epidemiological, sociological, or purely health-systems perspectives without a defined immunological component will fall outside the scope of this Research Topic. Topic editors: Kutty Selva Nandakumar, Jean Paul Akue, Yevgeniya Gartshteyn Source: https://www.frontiersin.org/research-topics/82174/immunological-complexity-of-lupus-across-diverse-populations-pathogenesis-biomarkers-and-translational-gaps