Risk factors for pulmonary complications in systemic lupus erythematosus: a meta-analysis of infectious pneumonia and interstitial lung disease.

2026-03-18
Frontiers in immunology 17
- Ze Yang
- Yanzuo Wu
- Zexuan Wu
- Shuo Huang
- Yongsheng Fan
- Jie Bao

PubMed: 41929493
DOI: 10.3389/fimmu.2026.1758316

Study Design

Type: Meta-Analysis
Sample size: n = 978
Population: patients with systemic lupus erythematosus (SLE)
Methods: Comprehensive literature search in seven electronic databases from database inception to September 2025; pooled effect sizes computed using appropriate model-based methods; evidence stratification framework integrating univariate associations and multivariate-adjusted results

Background

Pulmonary complications (PC), including infectious pneumonia (IP) and non-infectious interstitial lung disease (ILD), are major contributors of morbidity and mortality in systemic lupus erythematosus (SLE). As they are fundamentally different with respect to their respective etiologies and pathophysiology, we aimed to comprehensively identify and compare their risk factors.

Methods

We conducted a comprehensive literature search in seven electronic databases from database inception to September 2025. Pooled effect sizes were computed using appropriate model-based methods and thoroughly examined for heterogeneity. Our analytical approach advanced an evidence stratification framework that integrated both univariate associations and multivariate-adjusted results, which classified factors into four strata of findings: robust independent risk factors, preliminary independent risk factors, potential risk factors, and protective factors.

Results

In total, 16 studies comprising 6,978 participants yielded fundamentally distinct risk architectures. IP was predominantly driven by immunosuppression and systemic inflammation, with robust independent risk factors including advanced age, pulmonary involvement, high CRP/WBC, immunosuppressant use, and antibacterial drug use. In contrast, ILD was strongly driven by autoimmunity and vascular pathology, with preliminary independent risk factors including Raynaud's phenomenon, anti-Sm antibody positivity, high IgG and C4 levels. Most strikingly, serum IgG emerged as two strongly associated factors: low levels of serum IgG protected against IP, whereas high levels of serum IgG increased ILD risk.

Conclusion

This is the first study to systematically stratify PC risk factors in SLE, demonstrating their distinct pathogenesis. The hierarchic framework allows a shift from a uniform management mindset to individualized risk evaluation for the respective complications, supportimg targeted prevention and early detection strategies.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/view, identifier CRD420251020965.