Integrated inflammatory-immune-nutritional signatures differentiate lung phenotypes in systemic sclerosis

Area of Science:

• Rheumatology
• Pulmonology
• Immunology

Background:

• Systemic sclerosis (SSc) presents with varied lung issues, primarily interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH).
• The differences in systemic inflammatory, immune, and nutritional states across these SSc lung phenotypes are not fully understood.

Purpose of the Study:

• To define the integrated inflammatory-immune-nutritional signatures in SSc lung phenotypes.
• To validate these signatures using multivariable modeling and unsupervised clustering.

Main Methods:

• A retrospective study of 314 SSc inpatients (2018-2023) stratified into four lung phenotypes: ILD-/PAH-, ILD+/PAH-, ILD-/PAH+, and ILD+/PAH+.
• Analysis of routine laboratory data for inflammatory, nutritional, and immune markers.
• Multinomial logistic regression and k-means clustering for signature validation.

Main Results:

• ILD+/PAH+ patients exhibited higher systemic inflammation markers (ESR, hs-CRP, SII) compared to ILD-/PAH-.
• Anti-Scl-70 positivity was more common in ILD-containing phenotypes; immunoglobulin levels varied.
• Clustering identified three distinct groups driven by ESR, IgA, and triglycerides, with high stability.

Conclusions:

• SSc lung phenotypes, based on ILD/PAH co-occurrence, possess unique inflammatory-immune-nutritional signatures.
• The ILD+/PAH+ phenotype is associated with a significant systemic inflammatory state.
• Key biomarkers (ESR, triglycerides, IgA, autoantibodies) offer a framework for phenotype-based stratification in SSc.