# Clinical outcomes-dependent IgG epitope profiling in HTLV-1 reveals differential recognition of pathogen-derived antigens

## TL;DR

This study shows how HTLV-1 infection affects IgG responses to various pathogens differently depending on the clinical outcome, such as neurodegeneration or cancer.

## Contribution

The study introduces a high-density epitope microarray to profile IgG responses in HTLV-1 patients, revealing distinct immune signatures linked to clinical outcomes.

## Key findings

- HTLV-1–infected individuals show significant remodeling of IgG responses compared to healthy controls.
- HAM/TSP patients exhibit broad and high-magnitude IgG responses, while ATLL patients show distinct epitope recognition patterns.
- Enhanced IgG responses to specific pathogens like Mycobacterium tuberculosis and Toxoplasma gondii align with known co-infection risks in HTLV-1.

## Abstract

Human T-lymphotropic virus type 1 (HTLV-1) infection presents a wide clinical spectrum ranging from lifelong asymptomatic carriage to severe inflammatory neurodegeneration (HAM/TSP) or adult T-cell leukemia/lymphoma (ATLL). Although IgG responses contribute to viral control and immunopathology, the extent to which HTLV-1 clinical outcomes shape pathogen-derived IgG repertoires remains unclear. In this study, we applied a high-density infectious-disease epitope microarray containing 4,345 linear epitopes from viral, bacterial, parasitic, and fungal pathogens to profile IgG responses in healthy controls (HCs), asymptomatic carriers (ACs), HAM/TSP patients, and ATLL patients. Signal intensities were quantified in arbitrary units, and recognized epitopes were evaluated using similarity clustering (80% identity threshold) to assess repertoire structure. HTLV-1–infected individuals exhibited extensive remodeling of humoral immunity, with marked differences in the breadth and intensity of IgG recognition across clinical groups. HAM/TSP patients displayed broad and high-magnitude responses consistent with chronic inflammation and heightened Th1 activation, whereas ATLL patients recognized the largest number of epitopes but with distinct patterns indicative of altered B-cell regulation. Enhanced IgG responses to Mycobacterium tuberculosis, Strongyloides stercoralis, Toxoplasma gondii, and Plasmodium species were consistent with known co-infection susceptibilities in HTLV-1. Epitope similarity analysis revealed hundreds of low-redundancy clusters across all groups, arguing against simple linear cross-reactivity and suggesting phenotype-specific reshaping of B-cell selection and idiotypic networks. These findings demonstrate that HTLV-1 infection produces distinct, clinically dependent IgG epitope signatures across multiple pathogen classes, with potential relevance for understanding HTLV-1 pathogenesis and informing future studies integrating epitope mapping with B-cell repertoire analysis.