# Galectin-1 levels do not predict outcomes in undifferentiated arthritis: a two-year prospective observational study

**Authors:** Cristina Valero-Martínez, Marisa Pardines-Ortiz, Nuria Montes, Ana M. Ortiz, Rosario García-Vicuña, Isidoro González-Alvaro, Ana Triguero-Martínez

PMC · DOI: 10.3389/fimmu.2026.1757168 · Frontiers in Immunology · 2026-02-11

## TL;DR

This study found that Galectin-1 levels do not reliably predict outcomes in patients with undifferentiated arthritis over two years.

## Contribution

The novel contribution is the demonstration that Galectin-1 lacks predictive value in undifferentiated arthritis prognosis.

## Key findings

- Baseline and longitudinal Gal-1 levels were not associated with disease progression or activity in undifferentiated arthritis.
- Gal-1 levels remained stable despite clinical improvement, suggesting limited utility as a biomarker.
- Lower Gal-1 levels were observed in patients progressing to spondyloarthritis, indicating possible disease-specific modulation.

## Abstract

Undifferentiated arthritis (UA) represents an early and heterogeneous phase of inflammatory joint disease that may evolve into defined rheumatic conditions. This phase is characterized by immune dysregulation with loss of tolerance and early autoantibody production. Despite extensive research, reliable biomarkers for early diagnosis and prognosis remain lacking. Galectin-1 (Gal-1), an immunomodulatory lectin with anti-inflammatory properties, has been reported to be elevated in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study aimed to evaluate the diagnostic and prognostic value of serum Gal-1 levels in UA patients over a two-year follow-up.

This study analyzed patients from the observational PEARL study, that were classified as UA at baseline visit. After four standardized visits (0, 6, 12 and 24 months), in which biological samples, clinical, laboratory, and treatment data were systematically collected, a definitive diagnosis was established. Serum Gal-1 levels were measured by ELISA at all visits and analyzed in relation to clinical characteristics, final diagnosis, disease activity, and treatment intensity. Multivariate regression models were adjusted for relevant confounders.

A total of 139 patients were included. After two years, 44.6% (n=62/139) progressed to a chronic inflammatory rheumatic disease, mostly RA (67%; n=42/62), while 40.2% (n=56/139) remained as persistent UA. Baseline Gal-1 levels were not associated with seropositivity, functional disability or treatment intensity. A non-significant trend toward lower Gal-1 levels was observed in patients evolving to spondyloarthritis (SpA) whereas no major differences were observed among other diagnostic groups. Over the two-year follow-up, Gal-1 levels remained largely stable across all diseases and did not correlate with disease activity despite significant clinical improvement.

Overall, Gal-1 showed stable serum levels irrespective of disease activity or outcome, with limited predictive or monitoring value in UA. Lower concentrations observed in SpA suggest disease-specific modulation.

## Linked entities

- **Proteins:** galectin-1 (galectin-1)
- **Diseases:** rheumatoid arthritis (MONDO:0008383), systemic lupus erythematosus (MONDO:0007915), spondyloarthritis (MONDO:0005095)

## Full-text entities

- **Genes:** LGALS1 (galectin 1) [NCBI Gene 3956] {aka GAL1, GBP}, SAA [NCBI Gene 6287], IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CA8 (carbonic anhydrase 8 (inactive)) [NCBI Gene 767] {aka CA-RP, CA-VIII, CALS, CAMRQ3, CARP, SCAR34}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, PADI4 (peptidyl arginine deiminase 4) [NCBI Gene 23569] {aka PAD, PAD4, PADI5, PDI4, PDI5}, IL23A (interleukin 23 subunit alpha) [NCBI Gene 51561] {aka IL-23, IL-23A, IL23P19, P19, SGRF}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314] {aka CHDS6, MMP-3, SL-1, STMY, STMY1, STR1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** inflammatory musculoskeletal symptoms (MESH:D009140), autoimmune diseases (MESH:D001327), functional (MESH:D003291), IMIDs (MESH:C567355), SpA (MESH:D013167), osteoarthritis (MESH:D010003), PsA (MESH:D015535), immune dysregulation (OMIM:614878), septic (MESH:D001170), SLE (MESH:D008180), systemic sclerosis (MESH:D012595), Arthritis (MESH:D001168), inflammation (MESH:D007249), RA (MESH:D001172), CTD (MESH:D003240), reactive arthritis (MESH:D016918), Sjogren's syndrome (MESH:D012859), ACPA (MESH:C536207), inflammatory joint disease (MESH:D007592), RF (MESH:D001171), arthralgia (MESH:D018771), Disease modifying anti-inflammatory drugs (MESH:D000092582), chronic inflammatory rheumatic diseases (MESH:D012213), radiographic damage (MESH:D000089202), rheumatic (MESH:D012216)
- **Chemicals:** MTX (MESH:D008727), Anti-citrullinated protein (-), Sulfasalazine (MESH:D012460), poly-N-acetyllactosamine (MESH:C037199), HCQ (MESH:D006886), carbohydrate (MESH:D002241), Leflunomide (MESH:D000077339)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12932545/full.md

## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932545/full.md

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Source: https://tomesphere.com/paper/PMC12932545