Chromosomal Radiosensitivity in Sjögren's Syndrome with and Without Concomitant Malignancy

Connective tissue diseases have long been hypothesized to confer increased radiosensitivity and radiotherapy-related toxicity, although findings vary between disease entities. In a previous institutional study, we found increased radiosensitivity in patients suffering from systemic lupus erythematosus (SLE), primarily in patients with concomitant malignancy. We therefore investigated Sjögren's syndrome, an autoimmune disease for which evidence has been limited. Ex vivo chromosomal radiosensitivity was assessed in 45 patients with Sjögren's syndrome (27 non-oncological, 18 oncological) by three-color fluorescence in situ hybridization after 2 Gy irradiation of G0 peripheral blood lymphocytes. Results were compared with 211 healthy controls, 129 breast cancer patients, and the previously characterized SLE cohorts (37 non-oncological, 33 oncological). Demographic, clinical, serological, and treatment-related associations were explored in 31 deeply phenotyped patients. Radiosensitivity was significantly increased in non-oncological Sjögren patients (0.527 breaks per metaphase (B/M)) compared with healthy controls (0.411 B/M; p < 0.001) and non-oncological SLE patients (0.404 B/M; p = 0.001), and it remained similarly elevated in oncological Sjögren patients (0.527 B/M), whereas in SLE increased radiosensitivity was predominantly associated with concomitant malignancy. High-grade anti-SSB positivity was associated with increased radiosensitivity in the unadjusted analysis (p = 0.016), but did not withstand correction for multiple testing (q = 0.124). Sjögren's syndrome is associated with increased ex vivo chromosomal radiosensitivity, with no further apparent increase in patients with concomitant malignancy. This pattern differs from SLE and may suggest a stronger contribution of disease-associated factors. High-grade anti-SSB positivity may represent a relevant serological signal in relation to radiosensitivity, but requires validation in larger cohorts. These findings support closer consideration of individual radiosensitivity in Sjögren's syndrome and highlight the need for prospective studies integrating ex vivo radiosensitivity with radiotherapy-related toxicity and treatment outcomes in this patient population.