Background Periprosthetic joint infection (PJI) can sometimes be difficult to diagnose in patients with inflammatory arthritis because autoimmune disease activity and immunomodulatory treatment can alter systemic and synovial inflammatory responses. Diagnostic thresholds derived predominantly from patients with osteoarthritis may therefore produce false-positive or false-negative classifications in this population. Recent rheumatoid arthritis-specific cohorts and studies of synovial host-response biomarkers have expanded the evidence base beyond that available in earlier reviews. Methods We will conduct a systematic review and diagnostic test accuracy meta-analysis of studies evaluating serum, plasma, whole-blood, or synovial host-response biomarkers for hip or knee PJI in adults with inflammatory arthritis. We will search MEDLINE, Embase, Web of Science, Scopus, CINAHL, the Cochrane Library, CNKI, Wanfang, VIP, and SinoMed from inception without language restrictions. Two reviewers will independently screen records, extract data, and assess risk of bias and applicability using QUADAS-3; an adapted QUADAS-C assessment will additionally be used for direct comparative accuracy studies. For each biomarker and clinically coherent threshold group, paired sensitivity and specificity will be synthesized using bivariate random-effects models or hierarchical summary receiver operating characteristic models. Threshold effects, reference-standard incorporation bias, joint type, infection chronicity, disease activity, and immunosuppressive therapy will be examined through subgroup, meta-regression, and sensitivity analyses when data permit. Certainty of evidence will be assessed using GRADE for diagnostic tests. Discussion This review aims to determine whether commonly used and emerging host-response biomarkers retain adequate diagnostic performance in inflammatory arthritis, identify candidate population-specific thresholds that require prospective external validation, and clarify where evidence is insufficient for clinical implementation. Trial registration PROSPERO CRD420261449928.
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