Pronounced Diurnal Pattern of Salivary C-Reactive Protein (CRP) With Modest Associations to Circulating CRP Levels

Abstract

C-reactive protein (CRP), a humoral component of the innate immune system with important functions in host-defense, is extensively used as a sensitive biomarker of systemic inflammation. During inflammation, hepatocyte-derived CRP rises dramatically in the blood due to increased interleukin-6 (IL-6) levels. Reliable detection of CRP in saliva, instead of blood, would offer advantages regarding sampling procedure and availability but using saliva as a diagnostic body fluid comes with challenges. The aims of this study were to evaluate associations between salivary CRP, total protein levels in saliva and serum CRP. Furthermore, we examined associations with plasma IL-6, body mass index (BMI), tobacco smoking and age. Salivary CRP was investigated by ELISA in 107 middle-aged participants from the general population. We employed spectrophotometric determination of total protein levels. Correlation analyses were used for associations of salivary CRP with serum CRP (turbidimetry), plasma IL-6 (Luminex®), BMI and smoking habits. Salivary median CRP was 68% higher (p=0.009), and total protein levels were 167% higher (p<0.0001), in morning compared to evening saliva. The correlation coefficients between serum and salivary CRP were low to moderate, but stronger for evening than morning saliva. Plasma IL-6 correlated significantly with serum CRP (rs=0.41, p<0.01), but not with morning or evening salivary CRP. Non-smokers showed 103% higher salivary CRP levels (p=0.015), whereas serum CRP was independent of smoking status. As opposed to CRP in serum, salivary CRP was not associated with BMI. Salivary CRP was 90% higher among the age interval 60–69 years compared to subjects aged 45–59 (p=0.02) while serum CRP levels did not differ between the age groups. In conclusion, CRP in saliva did not straightforwardly reflect serum concentrations. This raises questions regarding adequate reflection of biological events. The pronounced diurnal salivary CRP pattern accentuates the importance of standardizing the time-point of sampling.

Comparison of passive drool and cotton‐based collection methods for salivary C‐reactive protein measurement

“…The salivary CRP levels were higher at wake‐up than 45 min post‐awakening, and this pattern was consistent across consecutive days and 4 weeks. The results are consistent with the previous studies on the stable and distinctive diurnal salivary CRP patterns in the general population across days (Izawa et al, 2013; Out et al, 2012; Wetterö et al, 2020). While diurnal variation is less often observed in serum samples (Meier‐Ewert et al, 2001), our present findings underscore the importance of accounting for the potential circadian rhythm of salivary CRP to ensure comparability of results across studies.…”

“…Unlike cytokines, salivary and serum CRP are likely to correlate as their origin is mainly in the liver (Slavish et al, 2015). While moderate to high positive correlations have been found between serum CRP and saliva CRP in some studies (Pay & Shaw, 2019;Wetterö et al, 2020), other studies (Dillon et al, 2010;Mirzaii-Dizgah et al, 2012) have found weak to nonsignificant correlations. The collection of noninvasive saliva samples is less expensive than serum samples and allows for repeated collections of this inflammatory biomarker and investigation of diurnal variations.…”

Comparison of C-Reactive Protein in Dried Blood Spots and Saliva of Healthy Adolescents

“…Salivary CRP has also been shown to be significantly higher in obese than in normal weight children ( 50 , 55 ), and to discriminate between lower and higher BMI in healthy adults when grouped in low sCRP vs. high sCRP ( 30 ). However, in the latter study, no significant correlation between BMI and the continuous sCRP measurement was detected ( 30 ), and Wettero et al ( 52 ) did not confirm a significant association between sCRP and BMI in middle-aged participants. To further evaluate the validity of both the correlation between DBS CRP and sCRP and each measurement itself, we split our sample into three BMI percentile range groups: A: ≤ 25, B: 26–74, C: ≥ 75.…”

Predictive Value of C-Reactive Protein for Early Postoperative Complications in Children After Hypospadias Surgery

“…The half-life of CRP in the circulation is very short, about 19 h, and decreases rapidly after the relief of the acute reaction. Therefore, CRP is widely used in clinical practice as an important marker of acute infection ( 33 ).…”