AUTHOR=Yan Qingran , Liu Bei , Yang Minjie , Li Qianqian , Wang Jieying , Li Ting , Lu Liangjing TITLE=Duration biased distribution of clinical and immunological phenotypes in active SLE JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1044184 DOI=10.3389/fimmu.2022.1044184 ISSN=1664-3224 ABSTRACT=Introduction

This study is aimed to map the clinical and immunological features of active lupus patients with different disease duration.

Methods

For clinical phenotype analysis, we enriched eligible medical records with active SLE (SLEDAI-2k≥8) from the Renji Lupus registry, a single-center database of hospitalized SLE patients with standard care, which covered national-wide patients. Patients with repeated hospitalization records in this enrichment were analyzed longitudinally as validation for the cross-sectional study above.

Results

We enriched a total of 1313 eligible records on active SLE (SLEDAI-2k≥8) for cross-sectional analysis. Stratified into four groups by a 5-year interval of disease duration, these active SLE patients showed a significantly shifting clinical phenotype along with the duration (ascending nephritis, pulmonary hypertension and descending fever, cutaneous symptoms, arthritis, and neuropsychiatric manifestations), especially in stratifications with disease onset age ≤ 45 years old. A longitudinal analysis of 55 patients with repeated hospitalizations for active lupus showed a similar trend. In the cross-sectional study of 222 records with full information on serology and lymphocyte subsets, peripheral B cell proportion, anti-dsDNA antibody, and serum IgG/IgM negatively correlated with duration, while CD8+ T cell proportion was positively correlated (P values, 0.029-4.8×10-17), which were supported by the sensitivity analysis in patient subgroups according to disease onset age and recent treatment. Multivariate linear regression identified duration as the only significant associator with both B cell and CD8+ T cell proportion (P values, 8.9×10-8 and 7.6×10-5, respectively). These duration biased immune phenotypes were highly consistent with the longitudinal observation in 14 patients with repeated hospitalizations.

Conclusions

Both clinical and immunological features of active SLE are significantly duration biased distributed, which merits further investigations in the evolution of SLE pathogenesis.