Salivary and Serum Inflammatory Profiles Reflect Different Aspects of Inflammatory Bowel Disease Activity

Abstract

Background Inflammatory bowel disease (IBD) can manifest both macroscopically and microscopically in the oral cavity; however, little is known about salivary changes in IBD. Therefore, this study aimed to assess salivary and circulatory inflammatory profiles in IBD and to compare their potential to reflect the presence and activity of IBD. Methods We measured 92 known inflammatory proteins in serum and in unstimulated and stimulated whole saliva samples from patients with IBD with active intestinal inflammation (n = 21) and matched control patients (n = 22) by proximity extension assay. Fifteen of the patients with IBD returned 10 to 12 weeks after treatment escalation for resampling. Results Sixty-seven of the proteins were detected in all 3 sample fluids but formed distinct clusters in serum and saliva. Twenty-one inflammatory proteins were significantly increased and 4 were significantly decreased in the serum of patients with IBD compared with that of the control patients. Two of the increased serum proteins, IL-6 and MMP-10, were also significantly increased in stimulated saliva of patients with IBD and correlated positively to their expressions in serum. None of the investigated proteins in serum or saliva were significantly altered by IBD treatment at follow-up. Overall, inflammatory proteins in serum correlated to biochemical status, and salivary proteins correlated positively to clinical parameters reflecting disease activity. Conclusions Saliva and serum inflammatory profiles in IBD share a similar composition but reflect different aspects of disease activity. The oral cavity reflects IBD through elevated IL-6 and MMP-10 in stimulated saliva.

MEFV and NLRP3 Inflammasome Expression Is Attributed to Immature Macrophages and Correlates with Serum Inflammatory Proteins in Crohn´s Disease Patients

“…The surgical CD patients in this study had a distinct serum protein profile compared to age-and sex-matched controls. Indeed, a subset of the elevated inflammatory proteins, IL-6, IL-8, CASP-8, and CXCL1, was also found among differently expressed serum proteins in random (non-surgical) CD cohorts using the same method as here (proximity extension assay) [34][35][36]. Moreover, we further show that two of these proteins, IL-6 and CASP-8, positively correlated with disease severity in our surgical CD cohort.…”

Proximity Extension Assay in Combination with Next-Generation Sequencing for High-throughput Proteome-wide Analysis

“…Olink® Explore is a powerful tool offering a high-multiplex protein biomarker platform with a tremendously high throughput capacity in combination with minimal sample volume requirements and with high specificity and sensitivity. The technology is based on the already proven high-multiplex PEA technology that has primarily been applied for screening of proteins in blood (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) but is now also used for other sample matrices e.g., CSF (32), cell (33)-and tissue (34) lysate, saliva (35), urine (36), interstitial fluid (37), cell culture media (38), peritoneal fluid (39), breast milk (40), BALF (41) and synovial fluid (42). Moreover, as minimal sample volumes are required, the technology has also been applied to samples of minimal sample volume, for example single cells (43), exosomes (44), dried blood spots (45), aqueous humour (46) and fineneedle biopsies (47).…”

“…The technology is based on the already proven high-multiplex PEA technology that has primarily been applied for screening of proteins in blood ( 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ) but is now also used for other sample matrices, e.g. , CSF ( 29 ), cell ( 30 ) and tissue ( 31 ) lysate, saliva ( 32 ), urine ( 33 ), interstitial fluid ( 34 ), cell culture media ( 35 ), peritoneal fluid ( 36 ), breast milk ( 37 ), BALF ( 38 ) and synovial fluid ( 39 ). Moreover, as minimal sample volumes are required, the technology has also been applied to samples of minimal sample volume, for example, single cells ( 40 ), exosomes ( 41 ), dried blood spots ( 42 ), aqueous humor ( 43 ) and fine-needle biopsies ( 44 ).…”

Changes in Salivary Parameters of Oral Immunity after Biologic Therapy for Inflammatory Bowel Disease

“…In this respect, Majster et al [41] compared the levels of inflammatory cytokines in the saliva and blood from IBD patients, and related them to disease activity. In contrast to significant changes in the serum levels of many cytokines, there were only slight changes in the saliva that did not associate with disease activity.…”