# Biomarkers over Time: From Visual Contrast Sensitivity to Transcriptomics in Differentiating Chronic Inflammatory Response Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

## TL;DR

This paper reviews how biomarkers have evolved to distinguish CIRS from ME/CFS, emphasizing the role of transcriptomics in improving diagnosis.

## Contribution

The paper introduces a chronological framework of biomarker development, particularly highlighting transcriptomic profiling for CIRS.

## Key findings

- Transcriptomic profiling, such as the GENIE platform, helps classify CIRS disease stages and differentiate it from other conditions.
- CIRS has a reproducible diagnostic framework, while ME/CFS lacks validated biomarkers and clear exposure-linked mechanisms.
- Many ME/CFS cases may actually represent undiagnosed CIRS due to overlapping symptoms and diagnostic ambiguity.

## Abstract

Chronic inflammatory response syndrome (CIRS) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are debilitating multisystem illnesses that share overlapping symptoms and molecular patterns, including immune dysregulation, mitochondrial impairment, and vascular dysfunction. This review provides a chronological synthesis of biomarker development in CIRS, tracing its evolution from early functional tests such as visual contrast sensitivity (VCS) to advanced transcriptomic profiling. Drawing on peer-reviewed studies spanning two decades, we examine the layered integration of neuroendocrine, immunologic, metabolic, and genomic markers that collectively support a multisystem model of innate immune activation specific to environmentally acquired illness. Particular focus is given to the Gene Expression: Inflammation Explained (GENIE) platform’s use of transcriptomics to classify disease stages and distinguish CIRS from other fatiguing conditions. While ME/CFS research continues to explore overlapping pathophysiologic features, it has yet to establish a unified diagnostic model with validated biomarkers or exposure-linked mechanisms. As a result, many patients labeled with ME/CFS may, in fact, represent unrecognized CIRS cases. This review underscores the importance of structured biomarker timelines in improving differential diagnosis and guiding treatment in complex chronic illness and highlights the reproducibility of the CIRS framework in contrast to the diagnostic ambiguity surrounding ME/CFS.