The acute phase response protein SERPINA3 is increased in tear fluid from the unaffected eyes of patients with unilateral acute anterior uveitis

Abstract

Background To identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls. Methods Thirteen patients (40.1 ± 16.2 years of age) with unilateral AAU, seven patients with unilateral bacterial keratitis (40.2 ± 15.3 years of age), and 14 healthy subjects (41.1 ± 11.6 years of age) were included. The tear proteome of affected eyes was compared with that of the unaffected eye or healthy controls. Proteins were identified by liquid chromatography tandem mass spectrometry and enzyme-linked immunosorbent assay. Results Relative protein ratios were detected and calculated for 272 unique proteins. Compared with healthy controls and the unaffected eye, the top upregulated proteins in AAU eyes were submaxillary gland androgen regulated protein 3B (SMR3B) and SMR3A. Similarly, the top upregulated proteins in bacterial keratitis were S100 calcium-binding protein A9 and orosomucoid 2. The acute phase response protein Serpin Family A Member 3 (SERPINA3) was increased in the healthy eye of AAU patients (P = 0.019) compared with healthy controls. Laser flare measurements in affected eyes of AAU patients showed positive logarithmic correlation with SERPINA3 in tear samples of the unaffected eye (P = 0.022). The use of SERPINA3 as a tear biomarker yielded a sensitivity of 85% and a specificity of 71% in detecting patients with AAU in the study population. Conclusions The acute phase response protein SERPINA3 was increased in tear samples of unaffected eyes of patients with unilateral AAU compared with healthy controls. This study highlights SERPINA3 as a potential biomarker for AAU. Future research should explore the dynamic properties of SERPINA3 in the tear fluid of active and quiescent uveitis eyes.

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“…Moreover, as we have reported recently, HCU had the strongest impact on the serum proteome of BASE-II participants, with PGLYRP2 being the main suppressed protein, and AGT, SERPINA6, FETUB the most induced. We found new HCU associations for 15 proteins, such as the acute-phase protein SERPINA3 106 , the monocyte and macrophage cell surface protein CD14 107 and the coagulation Factor 5 (F5). Furthermore, we compared effect sizes for age, sex, BMI, and hormonal contraceptive usage with those from our recently presented analysis of the CHRIS dataset 21 .…”

Differentially expressed genes in orbital adipose/connective tissue of thyroid-associated orbitopathy

“…Consistent with previous studies, we found elevated levels of CP and ATG in the adipose tissue and muscle of TAO patients. Existing data show that SERPINA3, an acute phase response protein, is involved in the pathogenesis of acute anterior uveitis, chronic obstructive pulmonary disease, Parkinson’s disease, Alzheimer’s disease, and coronary artery disease ( Eidet et al, 2021 ; Li et al, 2021 ; Sánchez-Navarro et al, 2021 ). There is also literature supporting that SERPINA3 can be expressed to promote cell proliferation, migration, and expression of inflammatory cytokines by NF-κB signaling pathways ( Liu et al, 2022 ).…”

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“…However, the potential limitations of these studies are also known, as the obtaining of aqueous and vitreous samples carried significant risk, and it remains unclear whether the expression of cytokines and chemokines in the serum is the same in the eye. Hence, new studies have explored the potential value of tear samples [ 20 , 21 , 22 , 31 , 45 , 46 ], as it is a non-invasive procedure; it is hypothesised that it could be used not only as a possible biomarker of uveitis activity but also as a predictive biomarker of response to the treatment, but the results have been controversial.…”