Anti-TSP-1 autoantibody linked to higher disease activity and dry eye in Sjögren disease

The study, published in Advances in Rheumatology, measured serum anti-thrombospondin-1 (anti-TSP-1) antibody levels by ELISA in 70 patients with Sjögren disease and 21 healthy controls. Patients with SjD had significantly higher antibody levels than the controls, with mean values of 10.63 ± 4.92 versus 7.64 ± 4.70, a difference the authors reported as statistically significant (t = 2.403, P = 0.019).

Positivity rates also differed between the groups. Among the SjD patients, 51.4% (36 of 70) tested positive for anti-TSP-1, compared with 28.6% (6 of 21) of the healthy controls. The authors note that the relationship between anti-TSP-1 antibodies and the clinical manifestations of Sjögren disease had not been fully clarified before this work, which motivated the analysis.

Within the patient group, elevated anti-TSP-1 antibody levels showed a positive correlation with IgG levels (r = 0.263, P = 0.029) and with ESSDAI, a clinical index of disease activity (r = 0.277, P = 0.020). The antibody levels were negatively correlated with complement C4 (r = -0.253, P = 0.035).

When patients were divided by antibody status, the anti-TSP-1-positive group exhibited a significantly higher prevalence of hypergammaglobulinemia and a significantly higher prevalence of xerophthalmia, or dry eye disease, than the anti-TSP-1-negative group (χ2 = 4.939, P = 0.026 for the xerophthalmia comparison). This suggests that the antibody may mark a specific clinical phenotype within Sjögren disease.

To test whether the antibody contributes independently to identifying SjD, the researchers performed binary logistic regression. Anti-TSP-1 positivity remained independently associated with SjD after adjusting for ANA, anti-SSA, and anti-SSB status, with an odds ratio of 8.333 (95% CI: 1.682–41.288, P = 0.009). The confidence interval is wide, reflecting the modest sample size of the study.

The authors conclude that elevated anti-TSP-1 antibody levels are associated with increased disease activity in SjD, and they suggest that anti-TSP-1 may serve as a potential adjunctive biomarker reflecting specific clinical phenotypes in Sjögren disease patients. They position the antibody as a complement to, rather than a replacement for, established markers such as ANA, anti-SSA, and anti-SSB.

Several limitations should be kept in mind when interpreting the findings. The study included a relatively small number of participants, 70 patients and 21 controls, and the reported correlations are weak to moderate. The authors also note that the article is being shared early as a peer-reviewed, accepted version that may be subject to further edits before the final version of record.

With those caveats, the study provides preliminary evidence that anti-TSP-1 positivity may help identify patients with higher disease activity and a greater burden of dry eye symptoms.

Subject of Research: Anti-thrombospondin-1 autoantibodies as a biomarker in Sjögren disease

Article Title: Anti-thrombospondin-1 autoantibody indicated increased disease activity and xerophthalmia incidence in Sjögren disease

Article References: Li, R., Li, Y., Guo, Y., Zhao, Y., Zhang, X., & Sun, X. (2026). Anti-thrombospondin-1 autoantibody indicated increased disease activity and xerophthalmia incidence in Sjögren disease. Advances in Rheumatology. https://doi.org/10.1186/s42358-026-00588-2

Image Credits: AI Generated

DOI: 10.1186/s42358-026-00588-2

Keywords: Sjögren disease, anti-TSP-1, autoantibody, xerophthalmia, ESSDAI, disease activity, ELISA, biomarker, IgG, complement C4, rheumatology, autoimmunity