Immunoglobulin G galactosylation levels are decreased in systemic sclerosis patients and differ according to disease subclassification.

ABSTRACT

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.