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Meta-Analysis
. 2023 Sep 18:14:1271383.
doi: 10.3389/fimmu.2023.1271383. eCollection 2023.

A systematic review and meta-analysis of neopterin in rheumatic diseases

Arduino A Mangoni  1   2 , Angelo Zinellu  3
Affiliations
Meta-Analysis

A systematic review and meta-analysis of neopterin in rheumatic diseases

Arduino A Mangoni et al. Front Immunol. .

Abstract

Introduction: Novel biomarkers of inflammation and oxidative stress might enhance the early recognition, management, and clinical outcomes of patients with rheumatic diseases (RDs). We assessed the available evidence regarding the pathophysiological role of neopterin, the oxidation product of 7,8-dihydroneopterin, a pteridine generated in macrophages activated by interferon-γ, by conducting a systematic review and meta-analysis of studies reporting its concentrations in biological fluids in RD patients and healthy controls.

Methods: We searched electronic databases for relevant articles published between inception and 31 August 2023. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation Working Group system, respectively.

Results: In 37 studies, when compared to healthy controls, RD patients had significantly higher concentrations of neopterin both in plasma or serum (standard mean difference, SMD=1.31, 95% CI 1.01 to 1.61; p<0.001; moderate certainty of evidence) and in the urine (SMD=1.65, 95% CI 0.86 to 2.43, p<0.001; I2 = 94.2%, p<0.001; low certainty of evidence). The results were stable in sensitivity analysis. There were non-significant associations in meta-regression and subgroup analysis between the effect size and age, male to female ratio, year of publication, sample size, RD duration, C-reactive protein, erythrocyte sedimentation rate, specific type of RD, presence of connective tissue disease, analytical method used, or biological matrix investigated (plasma vs. serum). By contrast, the effect size was significantly associated with the geographical area in studies assessing serum or plasma and with the type of RD in studies assessing urine.

Discussion: Pending additional studies that also focus on early forms of disease, our systematic review and meta-analysis supports the proposition that neopterin, a biomarker of inflammation and oxidative stress, can be useful for the identification of RDs. (PROSPERO registration number: CRD42023450209).

Systematic review registration: PROSPERO, identifier CRD42023450209.

Keywords: biomarkers; inflammation; metabolism; neopterin; oxidative stress; rheumatic diseases.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision

Figures

Figure 1
Figure 1
Biochemical pathways involved in the formation of neopterin.
Figure 2
Figure 2
PRISMA 2020 flow diagram.
Figure 3
Figure 3
Forest plot of studies examining neopterin concentrations in RD patients and healthy controls in serum/plasma.
Figure 4
Figure 4
Sensitivity analysis of the association between neopterin and RDs in serum/plasma.
Figure 5
Figure 5
Funnel plot of studies investigating the association between neopterin and RDs in serum/plasma after “trimming-and-filling”. Enclosed circles and free circles indicate dummy studies and genuine studies, respectively.
Figure 6
Figure 6
Forest plot of studies examining neopterin concentrations in RD patients and healthy controls in serum/plasma according to RD type.
Figure 7
Figure 7
Forest plot of studies examining neopterin concentrations in RD patients and healthy controls in serum/plasma according to the presence of connective tissue disease.
Figure 8
Figure 8
Forest plot of studies examining neopterin concentrations in RD patients and healthy controls in serum/plasma according to study continent.
Figure 9
Figure 9
Forest plot of studies examining neopterin concentrations in RD patients and healthy controls in serum/plasma according to the analytical method used.
Figure 10
Figure 10
Forest plot of studies examining neopterin concentrations in RD patients and healthy controls in serum/plasma according to the sample matrix used for assessment (plasma or serum).
Figure 11
Figure 11
Forest plot of studies examining neopterin concentrations in RD patients and healthy controls in urine.
Figure 12
Figure 12
Sensitivity analysis of the association between neopterin and RDs in urine.
Figure 13
Figure 13
Forest plot of studies examining neopterin concentrations in RD patients and healthy controls in urine according to RD type.
Figure 14
Figure 14
Forest plot of studies examining neopterin concentrations in RD patients and healthy controls in urine according to study continent.
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