Objectives: Scleroderma is a connective tissue
immune disease that features
collagen overproduction and can be categorized into two subtypes,
localized scleroderma (LSc) and
systemic sclerosis (SSc). SSc is clinically classified into two subsets: limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) SSc. The
immunoglobulin G-galactosylation (
IgG-Gal) ratio is abnormal in a number of
immune diseases and has not been evaluated in SSc.Method: The study recruited 93 LSc patients, 298 SSc patients, and 436 healthy controls. N-
glycans of purified
IgG were obtained from plasma and detected by tandem mass spectrometry. The
IgG-Gal ratio was measured by calculating the relative intensities of agalactosylated (G0), monogalactosyl (G1), and digalactosyl (G2) N-
glycans according to the formula G0/(G1 + G2 × 2). Furthermore, we examined whether the
IgG-Gal ratio differed between different subtypes of SSc.Results: The
IgG-Gal ratio was significantly higher in SSc patients (1.139 ± 0.870) than in LSc patients (0.485 ± 0.280) and controls (0.395 ± 0.190). The
IgG-Gal ratio successfully distinguished SSc patients from LSc and controls (area under the curve = 0.88 and 0.81, respectively). The
IgG-Gal ratio was significantly higher in dcSSc patients than in lcSSc patients and increased along with increases in modified Rodnan skin score (p = 6.03 × 10-5, Pearson's coefficient = 0.26) and erythrocyte sedimentation rate (p = 2.95 × 10-10, Pearson's coefficient = 0.38).Conclusion:
IgG-Gal ratios were abnormal in SSc patients and were associated with disease severity. The
IgG-Gal ratio therefore shows potential as a
biomarker for the diagnosis of SSc.