Chuanwei Zhang, Lijun Pang, Ziheng Zhu, Jianing Wang, Chuanbing Huang
Of 17,089 records before deduplication, 433 studies were included. Smoking/tobacco exposures dominated (n = 215, 49.7%), and rheumatoid arthritis was the most studied AIRD (n = 254, 58.7%). Twenty-five studies (5.8%) directly measured a pathway-proximal intermediary or omics readout, 79 (18.2%) measured an immune, serologic, complement or inflammatory biomarker, and 266 (61.4%) did not integrate an immune endpoint. Among 199 classifiable study-cell entries in four dense cells, mixed (n = 93) and positive/harmful (n = 91) directions were nearly balanced. Alternative priority-scoring schemes showed high rank concordance, and smoking/tobacco × systemic sclerosis remained within the top three priorities.
INTRODUCTION: Environmental exposures have been hypothesised to influence immune tolerance, but human studies of autoimmune inflammatory rheumatic diseases (AIRDs) often report exposure-disease associations without measuring immune intermediates. We mapped the structure, directionality, immune-mechanism integration and research priorities of this literature.
METHODS: Web of Science Core Collection and Scopus were searched on 18 May 2026 for English-language article/review records published during 2005-2025; non-original publications were excluded during eligibility assessment. Of 12,497 deduplicated records screened at title/abstract level, a predefined prioritisation strategy selected 2,632 reports for focused coding. Four high-density exposure-AIRD cells underwent SWiM-aligned direction-of-effect synthesis and focused OHAT-style risk-of-bias assessment, 64 cells underwent consensus research-priority scoring, and a post hoc four-level audit assessed immune-mechanism integration. No pooled effect estimates were calculated because exposures, outcomes, designs and analytical approaches were heterogeneous.
RESULTS: Of 17,089 records before deduplication, 433 studies were included. Smoking/tobacco exposures dominated (n = 215, 49.7%), and rheumatoid arthritis was the most studied AIRD (n = 254, 58.7%). Twenty-five studies (5.8%) directly measured a pathway-proximal intermediary or omics readout, 79 (18.2%) measured an immune, serologic, complement or inflammatory biomarker, and 266 (61.4%) did not integrate an immune endpoint. Among 199 classifiable study-cell entries in four dense cells, mixed (n = 93) and positive/harmful (n = 91) directions were nearly balanced. Alternative priority-scoring schemes showed high rank concordance, and smoking/tobacco × systemic sclerosis remained within the top three priorities.
DISCUSSION: This priority-based evidence map identifies a large but uneven association literature with limited direct immune-mechanism integration and supports more rigorous exposure assessment, immune phenotyping, mixture-aware analyses and geographically diverse research.