Urinary CD4⁺ T helper cells are a potential biomarker for tubulointerstitial nephritis in Sjögren's disease

Sjögren's Disease (SjD) is the most common connective tissue disease. An estimated 5-27% of patients have kidney involvement, usually in the form of tubulointerstitial nephritis (TIN). To date, there are no validated biomarkers for either diagnosis or assessment of therapeutic response. Since one of the hallmarks of TIN is leukocyturia, we aimed at investigating the potential role of urinary leukocytes as a diagnostic tool for SjD-TIN. We prospectively recruited 13 patients with SjD, that underwent kidney biopsy for suspected TIN. A multicolor flow cytometry panel was established to quantify 8 different urinary leukocyte populations. Our analyses showed, that urinary CD4⁺ T_H cells are increased in patients with SjD-TIN and can differentiate precisely between SjD-TIN and SjD-patients with other non-inflammatory kidney pathologies (SjD-CKD). In contrast, no other urinary cell population or clinical marker was able to differentiate between SjD-TIN and SjD-CKD. Furthermore, we found a very strong correlation between urinary CD4⁺ T_H cells and histological severity of TIN. Finally, during longitudinal follow up of 8 SjD-TIN patients undergoing immunosuppressive therapy, we saw a large and significant drop in urinary CD4⁺ T_H cells in parallel with clinical and histological improvement. Taken together our data suggest, that urinary CD4⁺ T_H cells might be a novel biomarker for diagnosis and follow up of SjD-TIN and might help to guide treatment decisions.