Causal relationship between immune cells and post-viral fatigue syndrome: a Mendelian randomization study

Abstract:

Background: Accumulating evidence has hinted at a correlation between immune cells and post-viral fatigue syndrome (PVFS). However, it is still ambiguous whether these associations indicate a causal connection.

Objective: To elucidate the potential causal link between immune cells and PVFS, we performed a two-sample Mendelian randomization (MR) study.

Methods: We obtained summary data on PVFS cases (Ncase = 195) and controls (Ncontrol = 382,198) from the FinnGen consortium. Additionally, we retrieved comprehensive statistical information on 731 immune cell features. Our analysis encompassed both forward and reverse MR approaches. To ensure the reliability and validity of our findings, we conducted rigorous sensitivity analyses, addressing issues of robustness and heterogeneity.

Result: Our study presents compelling evidence of a probable causal link between immune cells and PVFS. Notably, we have pinpointed 28 distinct types of immune cell traits that potentially exhibit a causal association with PVFS. Among a pool of 7 31 immune cell traits, we identified 28 immune cell types that exhibited a potential causal association with PVFS. These included 9 B cells, 1 conventional dendritic cell (cDC), 1 maturation stage of T cell, 3 myeloid cells, 9 T, B, NK, and monocyte cells (TBNK), and 5 regulatory T cells (Treg).

Conclusion: Through genetic analyses, our study has unveiled profound causal connections between specific types of immune cells and PVFS, offering valuable guidance for forthcoming clinical investigations.

Source: Wang Z, Bai Z, Sun Y. Causal relationship between immune cells and post-viral fatigue syndrome: a Mendelian randomization study. Virol J. 2025 May 30;22(1):171. doi: 10.1186/s12985-025-02809-4. PMID: 40448142; PMCID: PMC12124062. https://pmc.ncbi.nlm.nih.gov/articles/PMC12124062/ (Full text)

Deep Immunophenotyping in ME/CFS Using Spectral Flow Cytometry

Abstract:

Immune dysfunction is reported to play a significant role in the etiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To gain an understanding of the underlying immune abnormalities associated with this complex condition, a comprehensive approach for characterizing immune cell subsets and their inferred functional states is essential.

We developed a high-dimensional flow cytometry method that enables detailed immunophenotyping of peripheral blood mononuclear cells (PBMCs) from ME/CFS patients. By simultaneously measuring over 40 markers on individual cells within one sample, this approach provides a comprehensive assessment of immune cell subsets, incorporating effector or functional states, to enable assessment of their potential roles in disease pathogenesis.

Source: Gibson A, Chometon TQ, Damani T, Brooks AES. Deep Immunophenotyping in ME/CFS Using Spectral Flow Cytometry. Methods Mol Biol. 2025;2920:59-82. doi: 10.1007/978-1-0716-4498-0_5. PMID: 40372678. https://link.springer.com/protocol/10.1007/978-1-0716-4498-0_5

Quantitative Proteomics on Immune Cells of ME/CFS Patients Using SWATH-MS

Abstract:

Proteomics is one of the “omics” disciplines that has provided molecular insights into the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here we describe a complete SWATH-MS workflow for the quantitative profiling of proteins extracted from peripheral mononuclear blood cells to investigate proteomic alterations in ME/CFS. This workflow covers all steps of sample preparation, data acquisition, and data analysis.

We describe the process of generating a comprehensive spectral library from a pre-fractionated peptide reference sample followed by the acquisition of DIA data sets of individual samples using a 5600+ TripleTOF mass spectrometer. Examples of both library-based and library-free data analysis pipelines are presented based on the PeakView/MarkerView software package (commercial) and DIA-NN (free) software respectively.

Source: Kumar A, Peppercorn K, Kleffmann T. Quantitative Proteomics on Immune Cells of ME/CFS Patients Using SWATH-MS. Methods Mol Biol. 2025;2920:113-140. doi: 10.1007/978-1-0716-4498-0_8. PMID: 40372681. https://link.springer.com/protocol/10.1007/978-1-0716-4498-0_8