Background Soluble interleukin-2 receptor (sIL-2R) is known as an indicator for activation status of lymphocytes and could be a potential biomarker for disease activity of lymphoproliferative disorders and autoimmune diseases.
Objectives The aim of this study was to examine the association of sIL-2R with disease activity in patients with IgG4-related disease (IgG4-RD) and primary Sjögren's syndrome (pSS).
Methods Consecutive 45 patients with active, untreated IgG4-RD, 117 patients with pSS, and 10 patients with sicca syndrome (subjects with xerostomia with neither anti-SSA/SSB antibodies nor lymphocytic infiltration by lip biopsy) were enrolled. Disease activity of IgG4-RD and pSS was determined based on the IgG4-RD responder index (IgG4-RD RI) score and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score, respectively. The association of sIL-2R with disease activity was analyzed.
Results The levels of sIL-2R and serum IgG were significantly higher in both IgG4-RD (709U/mL, and 1988mg/dL) and pSS (464U/mL, and 1851mg/dL) compared to sicca syndrome (276U/mL, and 1255mg/dL). Serum levels of IgG4, IgE, and circulating eosinophil counts were significantly higher in IgG4-RD (552mg/dL, 732IU/mL, and 366/mm3) compared to pSS (37mg/dL, 216IU/mL, and 157/mm3) and sicca syndrome (45mg/dL, 132IU/mL, and 137/mm3). On the other hand, the levels of serum IgA and IgM were significantly higher in pSS (312mg/dL, and 112mg/dL) compared to IgG4-RD (182mg/dL and 81mg/dL) and sicca syndrome (228mg/dL and 78mg/dL). The levels of serum C-reactive protein, lactate dehydrogenase, CH50, CC chemokine ligand (CCL17)/thymus and activation-regulated chemokines (TARC) were not different among the three groups. In patients with IgG4-RD, the baseline IgG4-RD RI scores significantly correlated with the levels of sIL-2R (ρ=0.715, p<0.0001), serum IgG (ρ=0.672, p<0.0001) and IgG4 (ρ=0.632, p<0.0001), but not serum IgE levels (ρ=0.290, p=0.082) and circulating eosinophil counts (ρ=0.149, p=0.335). In patients with pSS, the ESSDAI scores significantly correlated with the levels of sIL-2R (ρ=0.615, p<0.0001) and serum IgG (ρ=0.627, p<0.0001), but not the levels of serum IgA (ρ=0.169, p=0.073) and IgM (ρ=0.133, p=0.157). Furthermore, the number of affected organs positively correlated with sIL-2R levels in both IgG4-RD (ρ=0.725, p<0.0001) and pSS (ρ=0.559, p<0.0001). Receiver operating characteristic curve analysis demonstrated that sIL-2R was the most distinguishable biomarker for the presence of extra-dacryosialadenitis lesions in patients with IgG4-RD, compared to serum IgG and IgG4, with a cut-off value of 424 U/mL (AUC=0.917, p<0.0001), and in patients with pSS with 513 U/mL (AUC=0.894, p<0.0001). The sIL-2R levels in patients with IgG4-RD decreased significantly after glucocorticoid treatment. Notably, the cases which could be followed up at disease relapse or exacerbation showed the re-elevation of sIL-2R levels.
Conclusions Soluble IL-2R level is a biomarker for disease activity, in particular for the extent of organ involvements and extra-dacryosialadenitis lesions in patients with IgG4-RD and pSS. Furthermore, sIL-2R level could be useful for longitudinal disease monitoring in patients with IgG4-RD.
Acknowledgements We sincerely thank all the physicians and others caring for the patients enrolled in this study.
Disclosure of Interest None declared