Proteomics of saliva, plasma, and salivary gland tissue in Sjögren's syndrome and non-Sjögren patients identify novel biomarker candidates

Sembler-Møller, Maria Lynn; Belstrøm, Daniel; Locht, Henning; Pedersen, Anne Marie Lynge

doi:10.1016/j.jprot.2020.103877

Cited by 28 publications

(28 citation statements)

References 29 publications

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“…Furthermore, TRIM proteins are involved in recognition of pathogens and regulation of transcriptional pathways in host defense [7]. In a recently published study of ours, we identified a panel of upregulated salivary proteins including neutrophil elastase, calreticulin, TRIM29, clusterin and vitronectin [8]. Among this panel of potential protein biomarker candidates, additional statistical analyses presented in this brief report shows that upregulated TRIM29 seems to represent a remarkably good marker for pSS when combined with presence of anti-SSA/Ro in serum.…”

Section: Introductionmentioning

confidence: 93%

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Combined serum anti-SSA/Ro and salivary TRIM29 reveals promising high diagnostic accuracy in patients with primary Sjögren’s syndrome

et al. 2021

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Objectives To determine the diagnostic potential of simultaneous presence of serum anti-SSA/Ro and upregulated salivary protein biomarkers in patients with primary Sjögren’s syndrome (pSS). Methods Previous proteomics data on the intensity of neutrophil elastase, calreticulin, tripartite motif containing protein 29 (TRIM29), clusterin and vitronectin provided basis for performing extended analysis. Protein data was obtained by liquid chromatography tandem mass spectrometry technique in whole saliva from 24 patients with pSS and 16 patients having symptoms of pSS, but not fulfilling the American College of Rheumatology/European League against Rheumatism classification criteria (non-pSS). Serum anti-SSA/Ro antibody was measured using enzyme-linked immunosorbent assays. Receiver operating characteristic curve (ROC) value was calculated for combined biomarkers. Results Simultaneous presence of serum anti-SSA/Ro and upregulated salivary TRIM29 provided the most optimal combination with an area under curve (AUC) of 0.995 (95% CI 0.98–1.00, p = 2.0E-7 and standard error 0.007) and combinations of sensitivity and specificity within the interval of 91–100%. ROC analysis showed that salivary levels of TRIM29 alone enabled differentiation between pSS and non-pSS with an area under curve (AUC) of 0.88 (95%CI 0.77–1.00). All patients with pSS and 3 non-pSS patients were serum anti-SSA/Ro positive. Conclusions Simultaneous presence of serum anti-SSA/Ro and upregulated salivary TRIM29 provided a high diagnostic accuracy exceeding that of currently available tools used in pSS diagnostics. This biomarker combination represents a promising less invasive diagnostic tool for pSS. The clinical applicability of TRIM29 needs further testing in independent cohorts using relevant analytical techniques.

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Section: Introductionmentioning

confidence: 93%

“…The study design and population has previously been described in details [8]. Prior to inclusion, all patients received oral and written information and signed an informed consent.…”

Section: Study Design and Populationmentioning

confidence: 99%

Combined serum anti-SSA/Ro and salivary TRIM29 reveals promising high diagnostic accuracy in patients with primary Sjögren’s syndrome

et al. 2021

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“…Studies on proteomic profile of saliva or tears through mass spectrometry has been used as another method to identify biomarkers in these secretes which may have a diagnostic potential for pSS (132)(133)(134). Although some molecules have been found to be promising diagnostic markers for pSS in different studies, the results of these proteomic analyses are not completely convincing (135).…”

Section: Need For New Biological Markersmentioning

confidence: 99%

Management of Sjögren's Syndrome: Present Issues and Future Perspectives

et al. 2021

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In view of the new possibilities for the treatment of primary Sjögren's syndrome (pSS) given by the availability of new biotechnological agents targeting the various molecular and cellular actors of the pathological process of the disease, classification criteria aimed at selecting patients to be enrolled in therapeutic trials, and validated outcome measures to be used as response criteria to these new therapies, have been developed and validated in the last decades. Unfortunately, the therapeutic trials so far completed with these new treatments have yielded unsatisfactory or only partially positive results. The main issues that have been evoked to justify the poor results of the new therapeutic attempts are: (i) the extreme variability of the disease phenotypes of the patients enrolled in the trials, which are dependent on different underlying patterns of biological mechanisms, (ii) the fact that the disease has a long indolent course, and that most of the enrolled patients might already have irreversible clinical features. The advances in the research of new disease biomarkers that can better distinguish the different clinical phenotypes of patients and diagnose the disease in an earlier phase are also discussed.

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“…The major and minor salivary glands secrete an abundance of proteins belonging to classes such as the proline-rich proteins, α-amylases, defensins, mucins, salivary cystatins, and histatins [ 106 , 107 ]. Thousands of salivary proteins have been identified and quantified in a variety of diseases including oral cancer, head and neck squamous cell carcinoma, and Sjögren’s syndrome using mass spectrometry techniques [ 108 , 109 , 110 , 111 , 112 ]. It has been suggested that saliva contains approximately 40% of the potential protein biomarkers found in cancer, stroke, and cardiovascular disease [ 106 ].…”

Section: Salivamentioning

confidence: 99%

Clinical Proteomics of Biofluids in Haematological Malignancies

Dunphy

O’Mahoney

Dowling

et al. 2021

IJMS

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Since the emergence of high-throughput proteomic techniques and advances in clinical technologies, there has been a steady rise in the number of cancer-associated diagnostic, prognostic, and predictive biomarkers being identified and translated into clinical use. The characterisation of biofluids has become a core objective for many proteomic researchers in order to detect disease-associated protein biomarkers in a minimally invasive manner. The proteomes of biofluids, including serum, saliva, cerebrospinal fluid, and urine, are highly dynamic with protein abundance fluctuating depending on the physiological and/or pathophysiological context. Improvements in mass-spectrometric technologies have facilitated the in-depth characterisation of biofluid proteomes which are now considered hosts of a wide array of clinically relevant biomarkers. Promising efforts are being made in the field of biomarker diagnostics for haematologic malignancies. Several serum and urine-based biomarkers such as free light chains, β-microglobulin, and lactate dehydrogenase are quantified as part of the clinical assessment of haematological malignancies. However, novel, minimally invasive proteomic markers are required to aid diagnosis and prognosis and to monitor therapeutic response and minimal residual disease. This review focuses on biofluids as a promising source of proteomic biomarkers in haematologic malignancies and a key component of future diagnostic, prognostic, and disease-monitoring applications.

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Proteomics of saliva, plasma, and salivary gland tissue in Sjögren's syndrome and non-Sjögren patients identify novel biomarker candidates

Cited by 28 publications

References 29 publications

Combined serum anti-SSA/Ro and salivary TRIM29 reveals promising high diagnostic accuracy in patients with primary Sjögren’s syndrome

Combined serum anti-SSA/Ro and salivary TRIM29 reveals promising high diagnostic accuracy in patients with primary Sjögren’s syndrome

Management of Sjögren's Syndrome: Present Issues and Future Perspectives

Clinical Proteomics of Biofluids in Haematological Malignancies

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