Identifying inflammatory phenotypes associated with lung involvement in systemic sclerosis: k-means clustering approach

Objectiveto assess the prognostic impact of clusters of hematologic and biochemical indices on interstitial lung disease (ILD) and respiratory damage associated with systemic sclerosis (SSc)MethodsDesign: We conducted a cross-sectional, uncontrolled study. Participants and Settings: a cohort of pati...

Full description

Saved in:
Bibliographic Details
Main Authors: Laura Cano-García, Aimara García-Studer, Sara Manrique-Arija, Fernando Ortiz-Marquez, Rocío Redondo-Rodríguez, Paula Borregón-Garrido, Natalia Mena-Vázquez, Antonio Fernández-Nebro
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568683/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850186750458068992
author Laura Cano-García
Laura Cano-García
Aimara García-Studer
Aimara García-Studer
Aimara García-Studer
Sara Manrique-Arija
Sara Manrique-Arija
Sara Manrique-Arija
Fernando Ortiz-Marquez
Fernando Ortiz-Marquez
Fernando Ortiz-Marquez
Rocío Redondo-Rodríguez
Rocío Redondo-Rodríguez
Paula Borregón-Garrido
Paula Borregón-Garrido
Natalia Mena-Vázquez
Natalia Mena-Vázquez
Antonio Fernández-Nebro
Antonio Fernández-Nebro
Antonio Fernández-Nebro
author_facet Laura Cano-García
Laura Cano-García
Aimara García-Studer
Aimara García-Studer
Aimara García-Studer
Sara Manrique-Arija
Sara Manrique-Arija
Sara Manrique-Arija
Fernando Ortiz-Marquez
Fernando Ortiz-Marquez
Fernando Ortiz-Marquez
Rocío Redondo-Rodríguez
Rocío Redondo-Rodríguez
Paula Borregón-Garrido
Paula Borregón-Garrido
Natalia Mena-Vázquez
Natalia Mena-Vázquez
Antonio Fernández-Nebro
Antonio Fernández-Nebro
Antonio Fernández-Nebro
author_sort Laura Cano-García
collection DOAJ
description Objectiveto assess the prognostic impact of clusters of hematologic and biochemical indices on interstitial lung disease (ILD) and respiratory damage associated with systemic sclerosis (SSc)MethodsDesign: We conducted a cross-sectional, uncontrolled study. Participants and Settings: a cohort of patients with SSc (2013 ACR/EULAR criteria) were enrolled in the rheumatology unit of a tertiary hospital in southern Spain. Primary and secondary outcome measures: The primary outcomes were the presence of SSc-ILD and respiratory damage, assessed via the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI). Inflammatory biomarkers, including both CRP and hematological indices, were obtained. Patients were grouped based on inflammatory phenotypes derived from longitudinal CRP averages and through principal component analysis (PCA) with K-means clustering of cross-sectional variables. Multivariate models were constructed to identify factors associated with SSc-ILD and respiratory damage.ResultsAmong 83 patients with SSc, 33.7% had ILD, 30.1% had respiratory damage, and 28.9% were receiving immunosuppressive therapy. A persistent inflammatory phenotype during follow-up was associated with non-Caucasian ethnicity (OR 14.0) and SSc-ILD (OR 17.9). Cross-sectional inflammatory clusters were linked to SSc-ILD (OR 12.8) and damage measured by SCTC-DI (OR 1.2). PC-2, derived from CRP-based variables, was a better predictor of SSc-ILD (OR 3.0) than PC-1, which was based on hematological indices (OR 0.5, non-significant), especially in the presence of anti-Scl70+ antibodies (OR 19.1) and immunosuppressants (OR 42.2). The only variables associated with respiratory damage were average CRP during follow-up (OR 1.2), anti-Scl70+ (OR 7.7), and glucocorticoids (OR 0.2).ConclusionCRP-based variables seem to be better predictors of SSc-ILD and respiratory damage than hematological indices.
format Article
id doaj-art-4c7b1e837b9a4e269aba1474022e0d41
institution OA Journals
issn 1664-3224
language English
publishDate 2025-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-4c7b1e837b9a4e269aba1474022e0d412025-08-20T02:16:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15686831568683Identifying inflammatory phenotypes associated with lung involvement in systemic sclerosis: k-means clustering approachLaura Cano-García0Laura Cano-García1Aimara García-Studer2Aimara García-Studer3Aimara García-Studer4Sara Manrique-Arija5Sara Manrique-Arija6Sara Manrique-Arija7Fernando Ortiz-Marquez8Fernando Ortiz-Marquez9Fernando Ortiz-Marquez10Rocío Redondo-Rodríguez11Rocío Redondo-Rodríguez12Paula Borregón-Garrido13Paula Borregón-Garrido14Natalia Mena-Vázquez15Natalia Mena-Vázquez16Antonio Fernández-Nebro17Antonio Fernández-Nebro18Antonio Fernández-Nebro19Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainDepartamento de Medicina, Universidad de Málaga, Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainDepartamento de Medicina, Universidad de Málaga, Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainDepartamento de Medicina, Universidad de Málaga, Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainDepartamento de Medicina, Universidad de Málaga, Málaga, SpainObjectiveto assess the prognostic impact of clusters of hematologic and biochemical indices on interstitial lung disease (ILD) and respiratory damage associated with systemic sclerosis (SSc)MethodsDesign: We conducted a cross-sectional, uncontrolled study. Participants and Settings: a cohort of patients with SSc (2013 ACR/EULAR criteria) were enrolled in the rheumatology unit of a tertiary hospital in southern Spain. Primary and secondary outcome measures: The primary outcomes were the presence of SSc-ILD and respiratory damage, assessed via the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI). Inflammatory biomarkers, including both CRP and hematological indices, were obtained. Patients were grouped based on inflammatory phenotypes derived from longitudinal CRP averages and through principal component analysis (PCA) with K-means clustering of cross-sectional variables. Multivariate models were constructed to identify factors associated with SSc-ILD and respiratory damage.ResultsAmong 83 patients with SSc, 33.7% had ILD, 30.1% had respiratory damage, and 28.9% were receiving immunosuppressive therapy. A persistent inflammatory phenotype during follow-up was associated with non-Caucasian ethnicity (OR 14.0) and SSc-ILD (OR 17.9). Cross-sectional inflammatory clusters were linked to SSc-ILD (OR 12.8) and damage measured by SCTC-DI (OR 1.2). PC-2, derived from CRP-based variables, was a better predictor of SSc-ILD (OR 3.0) than PC-1, which was based on hematological indices (OR 0.5, non-significant), especially in the presence of anti-Scl70+ antibodies (OR 19.1) and immunosuppressants (OR 42.2). The only variables associated with respiratory damage were average CRP during follow-up (OR 1.2), anti-Scl70+ (OR 7.7), and glucocorticoids (OR 0.2).ConclusionCRP-based variables seem to be better predictors of SSc-ILD and respiratory damage than hematological indices.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568683/fullsystemic sclerosisinterstitial lung diseaseinflammationC-reactive proteinhematological indicesinflammatory biomarkers
spellingShingle Laura Cano-García
Laura Cano-García
Aimara García-Studer
Aimara García-Studer
Aimara García-Studer
Sara Manrique-Arija
Sara Manrique-Arija
Sara Manrique-Arija
Fernando Ortiz-Marquez
Fernando Ortiz-Marquez
Fernando Ortiz-Marquez
Rocío Redondo-Rodríguez
Rocío Redondo-Rodríguez
Paula Borregón-Garrido
Paula Borregón-Garrido
Natalia Mena-Vázquez
Natalia Mena-Vázquez
Antonio Fernández-Nebro
Antonio Fernández-Nebro
Antonio Fernández-Nebro
Identifying inflammatory phenotypes associated with lung involvement in systemic sclerosis: k-means clustering approach
Frontiers in Immunology
systemic sclerosis
interstitial lung disease
inflammation
C-reactive protein
hematological indices
inflammatory biomarkers
title Identifying inflammatory phenotypes associated with lung involvement in systemic sclerosis: k-means clustering approach
title_full Identifying inflammatory phenotypes associated with lung involvement in systemic sclerosis: k-means clustering approach
title_fullStr Identifying inflammatory phenotypes associated with lung involvement in systemic sclerosis: k-means clustering approach
title_full_unstemmed Identifying inflammatory phenotypes associated with lung involvement in systemic sclerosis: k-means clustering approach
title_short Identifying inflammatory phenotypes associated with lung involvement in systemic sclerosis: k-means clustering approach
title_sort identifying inflammatory phenotypes associated with lung involvement in systemic sclerosis k means clustering approach
topic systemic sclerosis
interstitial lung disease
inflammation
C-reactive protein
hematological indices
inflammatory biomarkers
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568683/full
work_keys_str_mv AT lauracanogarcia identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT lauracanogarcia identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT aimaragarciastuder identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT aimaragarciastuder identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT aimaragarciastuder identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT saramanriquearija identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT saramanriquearija identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT saramanriquearija identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT fernandoortizmarquez identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT fernandoortizmarquez identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT fernandoortizmarquez identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT rocioredondorodriguez identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT rocioredondorodriguez identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT paulaborregongarrido identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT paulaborregongarrido identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT nataliamenavazquez identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT nataliamenavazquez identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT antoniofernandeznebro identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT antoniofernandeznebro identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach
AT antoniofernandeznebro identifyinginflammatoryphenotypesassociatedwithlunginvolvementinsystemicsclerosiskmeansclusteringapproach