Lower total serum Immunoglobulin G is associated with impaired patient-reported health-related quality of life in systemic sclerosis: a prospective cross-sectional study

Systemic sclerosis (SSc) is a connective tissue disease characterized by immune dysregulation, fibrosis, and vasculopathy, frequently resulting in substantial impairment in health-related quality of life (HRQoL). Total serum immunoglobulin G (IgG), a central component of adaptive humoral immunity, may reflect cumulative disease burden, yet has not been previously studied in relation to patient-reported outcomes (PROs) in SSc. In this prospective cross-sectional study, 64 patients fulfilling classification criteria for SSc were evaluated. HRQoL was assessed using the Systemic Sclerosis Quality of Life Questionnaire (SScQoL), Health Assessment Questionnaire Disability Index (HAQ-DI), and visual analog scales (VAS) for pain and global patient - reported disease activity (PGA). Lower IgG levels were significantly associated with worse HRQoL across all instruments: SScQoL (Spearman's ρ = - 0.437, p = 0.0009), HAQ-DI (ρ = - 0.446, p = 0.0007), VAS pain (ρ = - 0.486, p = 0.0002), and PGA (ρ = - 0.584, p < 0.0001). These associations were consistent across major clinical subgroups, including those stratified by antibody status, interstitial lung disease, and skin involvement severity. In multivariable models adjusting for inflammation, fibrosis, and gastrointestinal symptoms, IgG remained an independent predictor of worse SScQoL (β = - 0.012, p = 0.003). Patients with gastrointestinal involvement had significantly lower IgG levels (p = 0.025). No differences in IgG or HRQoL were observed by immunosuppressive treatment status. These findings suggest that total serum IgG is inversely associated with patient-reported HRQoL in systemic sclerosis and may serve as a clinically relevant, treatment-independent biomarker of perceived disease burden.