Introduction/Objectives This study aimed to identify serum biomarkers that distinguish patients with acute calcium pyrophosphate (CPP) crystal arthritis from those with rheumatoid arthritis (RA). Methods This study included patients with acute CPP crystal arthritis and those with RA treated at a single centre. The screening set included 18 patients with acute CPP crystal arthritis and 12 patients with RA. Serum samples were collected from all patients. Additionally, paired samples were obtained from five patients with CPP crystal arthritis after the resolution of their arthritis. The validation set included 11 patients with CPP crystal arthritis and 13 with RA. Serum metabolites were profiled using gas chromatography–mass spectrometry (GC–MS). Results Orthogonal partial least squares discriminant analysis revealed good separation between patients with acute CPP crystal arthritis and those with RA and between the acute CPP crystal arthritis phase and the resolution phase in the same patients. A total of 101 metabolites were identified. β-Hydroxybutyrate (BHB) levels were significantly higher in patients with acute CPP crystal arthritis than in those with RA and were higher in the acute CPP crystal arthritis phase than in the resolution phase. In the validation cohort, BHB consistently distinguished acute CPP crystal arthritis from RA, with an area under the receiver operating characteristic curve of 0.748, sensitivity of 90.9%, and specificity of 69.2%. Conclusions BHB is a potential diagnostic biomarker for distinguishing acute CPP crystal arthritis from RA. These findings highlight the potential of metabolomic analysis as a non-invasive diagnostic approach for CPP crystal deposition disease.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Key Points • Serum metabolomic profiling identified distinct metabolic signatures distinguishing acute CPP crystal arthritis from rheumatoid arthritis. • β-Hydroxybutyrate was a potential differential biomarker between acute CPP crystal arthritis and RA. • Alterations in ketone body metabolism may contribute to crystal-induced inflammation. </entry> </row> </tbody> </tgroup> </Table>

Serum β-hydroxybutyrate as a diagnostic biomarker distinguishing acute calcium pyrophosphate crystal arthritis from rheumatoid arthritis

期刊论文
发表日期：

2026年3月7日

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Soshi Takahashi,
Miho Takahashi,
Masakazu Shinohara,
Jun Saegusa,
Shunichi Kumagai

摘要

Introduction/Objectives

This study aimed to identify serum biomarkers that distinguish patients with acute calcium pyrophosphate (CPP) crystal arthritis from those with rheumatoid arthritis (RA).

Methods

This study included patients with acute CPP crystal arthritis and those with RA treated at a single centre. The screening set included 18 patients with acute CPP crystal arthritis and 12 patients with RA. Serum samples were collected from all patients. Additionally, paired samples were obtained from five patients with CPP crystal arthritis after the resolution of their arthritis. The validation set included 11 patients with CPP crystal arthritis and 13 with RA. Serum metabolites were profiled using gas chromatography–mass spectrometry (GC–MS).

Results

Orthogonal partial least squares discriminant analysis revealed good separation between patients with acute CPP crystal arthritis and those with RA and between the acute CPP crystal arthritis phase and the resolution phase in the same patients. A total of 101 metabolites were identified. β-Hydroxybutyrate (BHB) levels were significantly higher in patients with acute CPP crystal arthritis than in those with RA and were higher in the acute CPP crystal arthritis phase than in the resolution phase. In the validation cohort, BHB consistently distinguished acute CPP crystal arthritis from RA, with an area under the receiver operating characteristic curve of 0.748, sensitivity of 90.9%, and specificity of 69.2%.

Conclusions

BHB is a potential diagnostic biomarker for distinguishing acute CPP crystal arthritis from RA. These findings highlight the potential of metabolomic analysis as a non-invasive diagnostic approach for CPP crystal deposition disease.

Key Points

• Serum metabolomic profiling identified distinct metabolic signatures distinguishing acute CPP crystal arthritis from rheumatoid arthritis.

• β-Hydroxybutyrate was a potential differential biomarker between acute CPP crystal arthritis and RA.

• Alterations in ketone body metabolism may contribute to crystal-induced inflammation.