Galectin-1 and -9 (Gal1/9) are essential mediators of immune-inflammatory responses, which makes these proteins potential biomarkers for immune-mediated diseases (IMIDs), such as rheumatoid arthritis (RA), psoriasis (PS), psoriatic arthritis (PsA), inflammatory bowel disease, and systemic lupus erythematosus (SLE). Our aim was to evaluate plasma Gal1/9 differences between IMID patients and healthy donors (HD). We analyzed 980 plasma samples divided into two analytical cohorts (600 discovery group and 380 validation group). Generalized linear models estimated Gal1/9 levels, adjusting for sex, age, storage time, and plate variability. In the overall IMID group, plasma Gal1 levels were comparable to those of HD, while Gal9 levels were significantly elevated. Levels varied across individual diseases: SLE patients consistently showed the highest Gal1/9 levels compared to both HD and other IMIDs, and RA patients had elevated Gal9 levels versus HD. Both Gal1 and Gal9 plasma levels correlated positively with higher disease activity, and Gal1 was higher in patients with longer disease duration. After adjustment for these confounders, SLE and RA patients maintained the highest Gal9 levels compared to HD. Our study demonstrates that Gal1 and Gal9 are differentially expressed across IMIDs, with particularly elevated levels in SLE, and both galectins are associated with disease activity.

The aim of this study was to identify single-nucleotide polymorphisms (SNPs) in bone remodeling-related genes associated with disease severity and bone mineral density (BMD) in early arthritis (EA) patients. For this purpose, the genotyping of 552 SNPs located in gene regions of semaphorins 4b, 4d, 4f, DKK1, 2 and 3, sclerostin, OPG, RANK and RANKL was performed using Immunochip from Illumina Inc. in 268 patients from the Princesa Early Arthritis Register Longitudinal (PEARL) study. Measurements of BMD and disease activity were chosen as outcome variables to select SNPs of interest. The relationships of SNPs with the BMD of the forearm, lumbar spine and hip (Hologic-4500 QDR) were analyzed by linear regression adjusted for age, sex, body mass index and presence of anti-citrullinated peptide antibodies (ACPAs). The association of each SNP with activity variables was analyzed by linear regression, logistic regression or ordered logistic regression according to the variable, and multivariate models were adjusted for potentially confounding variables, such as age, sex and presence of ACPAs. These analyses showed that four SNPs located in the genes coding for RANK (TNFRSF11A) and OPG (TNFRSF11B) were significantly associated with clinical variables of severity. SNP rs1805034 located in exon 6 of TNFRSF11A, which causes a non-synonymous (A/V) mutation, showed significant association with BMD and therefore may be considered as a possible biomarker of severity in RA patients. SNPs in the OPG gene showed an association with serum OPG levels and predicted disease activity after two years of follow-up.