# Expression of MicroRNA-155 and its associations with EBV serological markers and inflammatory cytokines in young lymphoma patients with evidence of active EBV infection

**Authors:** Lezan Medhat Mohammed, Payman S. Ali, Ali Qasim Taha, Luay M. Mohammad

PMC · DOI: 10.3389/ebm.2026.10869 · 2026-02-03

## TL;DR

This study finds that miR-155 levels are higher in young lymphoma patients with active EBV infection and are linked to inflammatory markers like IL-32.

## Contribution

The study identifies miR-155 as a potential non-invasive biomarker for EBV-related immune activation in young lymphoma patients.

## Key findings

- Serum miR-155 levels were significantly higher in lymphoma patients compared to healthy controls.
- miR-155 was strongly associated with EBV IgM positivity and inflammatory cytokines IL-18 and IL-32.
- IL-32 positivity was a strong independent predictor of elevated miR-155 levels.

## Abstract

The Epstein–Barr virus (EBV) is implicated in several lymphoproliferative disorders, particularly among children and adolescents who frequently experience primary EBV infection. MicroRNA-155 (miR-155), an oncogenic and immunoregulatory molecule, is known to participate in EBV-related immune modulation; however, its expression profile and relationship with EBV serological markers and inflammatory cytokines in young lymphoma patients remain insufficiently characterized. This cross-sectional observational study included 80 participants, comprising 40 young lymphoma patients with serological evidence of active EBV infection and 40 healthy controls. Serum EBV IgM and IgG levels were measured using ELISA, as were IL-18 and IL-32 concentrations, while serum miR-155 levels were quantified using qRT-PCR with an absolute quantification approach. The mean age of participants was 13.19 ± 2.51 years, and 55% were male. Serum miR-155 levels were significantly higher in lymphoma patients compared with controls (median: 1.13 vs. 0.43 ng/mL; p = 0.012). Elevated miR-155 expression was significantly associated with EBV IgM positivity (p < 0.001), IL-18 (p = 0.001), and IL-32 (p < 0.001). In multivariate logistic regression analysis, IL-32 positivity emerged as a strong independent predictor of elevated miR-155 levels (AOR = 19.02, p = 0.001). Receiver operating characteristic curve analysis demonstrated good discriminative performance of miR-155 (AUC = 0.87), with 87% sensitivity and 90% specificity at a cutoff value of ≥1.11 ng/mL. These findings indicate that serum miR-155 is significantly elevated in young lymphoma patients with serological evidence of active EBV infection and is statistically associated with inflammatory cytokines, particularly IL-32. miR-155 may represent a promising non-invasive biomarker reflecting EBV-related immune activation, although tissue-based EBV confirmation and mechanistic studies are required to establish causality.

## Linked entities

- **Proteins:** IL18 (interleukin 18), IL32 (interleukin 32)
- **Diseases:** lymphoma (MONDO:0003659)

## Full-text entities

- **Genes:** JAK1 (Janus kinase 1) [NCBI Gene 3716] {aka AIIDE, JAK1A, JAK1B, JTK3}, PDLIM7 (PDZ and LIM domain 7) [NCBI Gene 9260] {aka LMP1, LMP3}, IL32 (interleukin 32) [NCBI Gene 9235] {aka IL-32alpha, IL-32beta, IL-32delta, IL-32gamma, NK4, TAIF}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, JUNB (JunB proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3726] {aka AP-1}, MIR155HG (MIR155 host gene) [NCBI Gene 114614] {aka BIC, BIC-155, LncRNA-SERB, MIRHG2, NCRNA00172, miPEP155}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, STAT4 (signal transducer and activator of transcription 4) [NCBI Gene 6775] {aka DPMC, SLEB11}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}
- **Diseases:** infection (MESH:D007239), viral infections (MESH:D014777), Co-infection (MESH:D060085), diffuse large B-cell lymphoma (MESH:D016403), B-cell lymphomas (MESH:D016393), EBV-associated lymphoproliferative disorders (MESH:D008232), Lymphoma (MESH:D008223), cancers (MESH:D009369), EBV Infection (MESH:D020031), inflammation (MESH:D007249), hematologic malignancies (MESH:D019337), Hodgkin lymphoma (MESH:D006689), Burkitt lymphoma (MESH:D002051), Autoimmune disorders (MESH:D001327)
- **Chemicals:** EDTA (MESH:D004492)
- **Species:** Homo sapiens (human, species) [taxon 9606], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12909255/full.md

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Source: https://tomesphere.com/paper/PMC12909255