Subgroups of Sjögren's disease: are they of any help?

Sjögren's disease is a chronic, systemic autoimmune disease with heterogenous disease manifestations. To investigate the different subgroups of this multifaceted disease, several research groups have stratified patients on the basis of symptoms, molecular pathways, or both. Previous hierarchical cluster or latent class analyses, based on five patient-reported outcomes (dryness, fatigue, pain, anxiety, and depression), revealed either three or four clusters of patients, classed as low symptom burden, high symptom burden, and dryness dominant with or without fatigue and pain. 1 Tarn JR Howard-Tripp N Lendrem DW et al. Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials. Lancet Rheumatol. 2019; 1: e85-e94 Summary Full Text Full Text PDF PubMed Scopus (75) Google Scholar , 2 Lee JJ Park YJ Park M Yim HW Park SH Kwok SK Longitudinal analysis of symptom-based clustering in patients with primary Sjogren's syndrome: a prospective cohort study with a 5-year follow-up period. J Transl Med. 2021; 19: 394 Crossref PubMed Scopus (8) Google Scholar , 3 McCoy SS Woodham M Bartels CM et al. Symptom-based cluster analysis categorizes Sjögren's disease subtypes: an international cohort study highlighting disease severity and treatment discordance. Arthritis Rheumatol. 2022; 74: 1569-1579 Crossref PubMed Scopus (6) Google Scholar A 2024 proteomic and network analysis showed differential expression of chemokines, cytokines, and master transcription factors between four symptom-based clusters. 4 Berry JS Tarn J Casement J et al. Examining the biological pathways underlying clinical heterogeneity in Sjogren's syndrome: proteomic and network analysis. Ann Rheum Dis. 2024; 83: 88-95 Crossref PubMed Scopus (2) Google Scholar A latent class analysis of patients with systemic disease activity resulted in five clusters, which were distinguished by the presence of symptoms (pain and fatigue) and the organ system involved (articular or multiorgan). 5 Gairy K Knight C Anthony P Hoskin B Burden of illness among subgroups of patients with primary Sjögren's syndrome and systemic involvement. Rheumatology (Oxford). 2021; 60: 1871-1881 Crossref PubMed Scopus (8) Google Scholar Identification of distinct subgroups of Sjögren's disease by cluster analysis based on clinical and biological manifestations: data from the cross-sectional Paris-Saclay and the prospective ASSESS cohortsOn the basis of symptoms and clinical and biological manifestations, we identified three distinct subgroups of patients with Sjögren's disease with different prognoses. Our results suggest that these subgroups represent different heterogeneous pathophysiological disease mechanisms, stages of disease, or both. These findings could be of interest when stratifying patients in future therapeutic trials. Full-Text PDF Open Access