Does Eta Protein Differentiate Rheumatoid Arthritis from Psoriatic Arthritis?

AIM: The clinical symptoms and laboratory markers of Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA) can be very similar, so making a differential diagnosis between these two diseases is often difficult. Serological parameters to be used in differential diagnosis can guide the clinician. This study aimed to investigate the usability of 14-3-3η (eta) protein as a biomarker in the differential diagnosis of PsA and RA, and the relationships between eta protein and disease activity scores and joint erosions in PsA and RA. METHODS: 54 PsA patients, 53 RA patients, and 56 healthy individuals were included in this study. The ELISA (Enzyme-Linked ImunoSorbent Assay) kit was used as a quantitative sandwich enzyme immunoassay technique to detect human eta protein levels. Receiver- operating Characteristic (ROC) curves analysis was used to determine the sensitivity and specificity of the eta protein. RESULTS: Eta protein levels were found to be significantly higher in the RA group than in the PsA [B: -0.341, OR (95% CI): 0.711 (0.556-0.909), p: 0.007] and control [B: -0.225, OR (95% CI): 0.798 (0.641-0.995), p: 0.045] groups. Eta protein median values were significantly higher in patients with joint erosion than in those without [ß= 0.151, OR (95% CI): 1.163 (1.003-1.349), p: 0.046]. CONCLUSION: Eta protein levels are higher in the serum of RA patients than PsA and are associated with joint erosion. Eta protein may be a potential biomarker in the differential diagnosis of RA and PsA. It may represent a possible therapeutic step in the pathophysiological pathways in the development of joint erosion.

The thiol/disulfide balance is shifted towards oxidation in psoriatic arthritis compared to controls and is associated with higher disease activity.

OBJECTIVE: This study was designed to compare thiol/disulfide and ischemia-modified albumin (IMA) levels between psoriatic arthritis (PsA) and healthy controls and evaluate the correlation between these molecules and the disease activity scores used in PsA. METHODS: A total of 63 PsA patients and 49 healthy volunteers were included in the study. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), modified disease activity score 28 (DAS28), and Bath Ankylosing Spondylitis Functional Index (BASFI) scores were used as disease activity indices for PsA patients. Calculations of native thiol (-SH), disulfide (-SS), and total thiol (-SH+-SS) molecules were made by the automatic spectrophotometric method, and the albumin cobalt binding test was used to measure IMA levels. RESULTS: In the PsA group, -SS/-SH and -SS/(-SH+-SS) levels were higher and -SH/(-SH+-SS) levels were lower than in controls. In the linear regression analysis, a significant correlation relationship was detected between DAS28-erythrocyte sedimentation rate (ESR) and -SS/(-SH+-SS) (ß = 0.795, CI 95%, 0.196-1.395; P = .010), -SH/(-SH+-SS) (ß = -0.475, CI 95%, 0.114-0.836; P = .010) and IMA (ß = 3.932, CI 95%, 0.859-7.005; P = .013). Additionally, a significant correlation was detected between IMA and BASDAI and BASFI. CONCLUSION: In PsA, thiol/disulfide homeostasis has shifted in favor of disulfide as an oxidative indicator. Serum thiol/disulfide levels are correlated with PsA disease activity indices.

Serum netrin-1 levels are high in Rheumatoid arthritis associated interstitial lung disease.

BACKGROUND: Recent data show that netrin-1 has a role in development of pulmonary fibrosis. This study was aimed to investigate serum netrin-1 level and its relation to interstitial lung disease(ILD) in patients with rheumatoid arthritis (RA). METHOD: 42 RA patients with RA-ILD, 58 RA patients without RA-ILD (RA non-ILD group), and 61 healthy volunteers were included in this study. The modified DAS28-ESR score was used to calculate disease activity in RA patients. Using the quantitative immunoassay method, Serum netrin-1 levels were measured with an ELISA kit (Catalog number: E-EL-H2328; lab science, lot number: GZWTKZ5SWK, Texas, USA). RESULTS: The median value of netrin-1 was found to be significantly higher in the RA-ILD group (82.9 [59.9-124]) compared to both the RA non-ILD group(52.9 [49.5-73.1])(B = -0.006, OR = 0.994, CI 95 %=0.989-0.999, P = 0.018) and the control group(53.5 [49.5-87.5]) (B: -0.005, OR: 0.994, CI 95 %: 0.990-0.999, p: 0.022). A cut-off value of 61.78 for netrin-1 was found to have a sensitivity of 73.8 % and a specificity of 69 % for the diagnosis of RA-ILD (AUC [95 %Cl] = 0.771 [0.679-0.862], p < 0.0001).It was found that high serum netrin-1 level was strongly associated with the RA-usual interstitial pneumonia(UIP) pattern and poorly related to the RA-nonspecific interstitial pneumonia(NSIP) pattern compared to the RA non-ILD group. CONCLUSIONS: Netrin-1 is elevated in the serum of patients with RA-ILD, especially in the UIP pattern. Netrin-1 may be a potential candidate for predicting the development of RA-ILD that should be investigated in the pathophysiological and therapeutic fields..

Renal tubular estrogen ß receptors are expressed at high levels in small vessel vasculitis and are primarily localized in the distal tubule.

This study investigated the possible roles of renal estrogen receptors (ER) in glomerulonephritis associated with small vessel vasculitis. The relationships of ERs were investigated in antineutrophilic cytoplasmic antibody (ANCA)-associated glomerulonephritis and immunoglobulin A (IgA) nephropathy groups, which are small vessel vasculitis subtypes with two different glomerulonephritis development pathophysiologies. The design of this study was prepared as a retrospective cohort study. The study included 42 patients with ANCA-associated vasculitis and 18 with IgA nephropathy in the small vessel vasculitis group. For the control group, intact renal tissues of 28 patients who underwent nephrectomy due to renal cell carcinoma were used. Renal biopsy samples of the groups were stained with ER beta (ß) and ER alpha (α). Tubular ER ß expression score (TERßES) median values were found to be significantly higher in ANCA- associated vasculitis (B = 0.724, OR [95%CI]: 2.064 [1.141-3.731], p = .016) and IgA nephropathy (B = 0.898, OR [95%CI]: 2.454 [1.307-4.609], p = .005) than in intact kidney tissue. It was determined that tubular ERß was most frequently localized in the distal tubule at 57.9% and the second most common in the proximal tubule at 20.4%. The expression of tubular ERß is increased in glomerulonephritis due to small vessel vasculitis. Tubular ERßs are most commonly localized in the distal tubule. Further studies are needed to understand the physiological and pathophysiological effects of altered renal ER levels in small vessel vasculitis.

Renal tubular and glomerular estrogen receptor ß levels are lower in lupus nephritis than in familial Mediterranean fever-associated renal amyloidosis.

BACKGROUND: Estrogen has been thought to play an essential role in the disease pathogenesis of systemic lupus erythematosus, which is 9-10 times more prevalent in the female population. It has been shown that irregular estrogen/estrogen receptor signaling pathways may contribute to the pathophysiology of various renal diseases. In this study, we compared renal estrogen receptors between lupus nephritis, familial Mediterranean fever-associated renal amyloidosis, ANCA-associated nephritis, and intact kidney to investigate their role in the pathophysiology of renal diseases. METHODS: This study was designed as a retrospective cohort study. Thirty systemic lupus erythematosus patients with lupus nephritis, 12 familial Mediterranean fever amyloidosis and 10 ANCA-associated glomerulonephrites, and 14 individuals with normal renal histology were included in the study. RESULTS: Tubular estrogen receptor ß expression score was found to be significantly higher in the familial Mediterranean fever [5 (1-8)] group than in the lupus nephritis [0 (0-1)] (B = 1.385, OR = 3.996, CI %95 = 1.805-8.846, p = .001) and ANCA [4 (1-6.5)] (B = -1.431, OR = 0.239, CI 95% = 0.093-0.614, p = .003) groups. A significant correlation was found between serum creatinine values and tubular estrogen receptor ß expression score (OR = 0.565, CI 95% = 0.622-1.402, p < .0001). In ANCA-associated glomerulonephritis, a significant relationship was found between fibro cellular crescents in renal biopsy and glomerular estrogen receptor ß expression score (OR = 0.247, CI 95% = 0.11-0.999, p = .045) and tubular estrogen receptor ß expression score (OR = 0.282, CI 95% = -0.180-2.812, p = .026). CONCLUSIONS: This study showed that tubular estrogen receptor ß expression score was elevated in familial Mediterranean fever amyloidosis and correlated with serum creatinine levels and renal crescents.

14-3-3 η ETA protein as a potential marker of joint damage in gout.

INTRODUCTION: The aim of the study is to investigate serum levels of 14-3-3 η (ETA) protein in patients with gout and possible relations with joint damage. METHOD: This cross-sectional study included 43 gout patients and 30 control patients. RESULTS: Serum 14-3-3 η protein levels were significantly higher in gout patients (median [IQR], 3.1 [2.0] vs 2.2 [1.0], p = 0.007). In subgroup analyses of gout patients, serum 14-3-3 η protein levels did not differ between patients with and without a flare, tophaceous disease, elevated CRP and serum uric acid levels and a history of chronic kidney disease; however, were significantly higher in the patients with erosions (Median [IQR], 4.1 [2.7] vs 2.7 [1.5], p = 0.002). According to ROC curve, serum 14-3-3 η protein had 86.0% sensitivity and 30% specifity at a cut-off point of 1.7 ng/mL and had 74.7% sensitivity and 43.3% specifity at a cut-off point of 2.0 ng/mL. CONCLUSION: Our results demonstrated elevated levels of 14-3-3 η protein in gout patients which is more prominent in patients with erosive changes, implying role of 14-3-3 η protein in inflammatory and structural damage related pathways and suggesting a potential as a marker for disease severity.

Evaluation of thiol/disulfide homeostasis in rheumatoid arthritis and disease activity.

BACKGROUND: It has been suggested that the deterioration in the antioxidant defense system due to thiols may cause the pro-oxidant/antioxidant imbalance seen in rheumatoid arthritis (RA). This study was conducted to evaluate thiol/disulfide (-SH/-SS) homeostasis in patients with RA compared to healthy controls, and to validate the limited number of studies examining the relationship between Disease Activity Score-28 (DAS28) and thiol parameters. METHOD: A total of 100 individuals (mean age: 46.3 ± 12.03) consisting of 86 females and 14 males were included in the RA group, and a total of 100 individuals (mean age: 43.3 ± 10.96 years) consisting of 78 females and 22 males were included in the control group. DAS28 was used to assess RA disease activity. -SH/-SS homeostasis parameters were measured using the automated spectrophotometric method described by Erel and Neselioglu. RESULTS: While native thiol (-SH) (p:0.001), total thiol (-SH + -SS) (p < 0.0001) levels and -SH\(-SS + -SH) ratio (p: 0.018) were lower in the RA group compared to the healthy controls, disulfide (-SS) level (p: 0.005)), -SS\-SH (p: 0.001) and -SS\(-SS + -SH) (p: 0.002) ratios were found to be higher. In the control group and the group in remission (defined by DAS28 < 2.6), the median values of -SH (p:0.002) and -SS + -SH (p:0.0008) were found to be significantly higher, and the median value of -SS (p: 0.001) was found to be lower compared to the other DAS28 groups. While a negative correlation was found between DAS28 and -SH (r: -0.243, p: 0.007), a positive correlation was found between DAS28 and -SS (r: 0.316, p: 0.0003), -SS\-SH (r:0.229, p: 0.002) and -SS\(-SS + -SH) (r: 0.285, p: 0.0009). CONCLUSIONS: The plasma thiol antioxidant pool was decreased in RA compared to healthy controls and those with active disease compared to those in remission.

14-3-3η Proteins as a Diagnostic Marker, Disease Activation Indicator, and Lymphoma Predictor in Patients with Primary Sjögren Syndrome.

BACKGROUND: Primary Sjögren syndrome (PSS) is a chronic, autoimmune, and lymphoproliferative disease of the connective tissue. In patients with PSS, the risk of developing B-cell non-Hodgkin lymphoma (NHL) increases dramatically, with a prevalence of approximately 5%. The 14-3-3 protein isoforms are phospho-serin/phospho-threonine binding proteins associated with many malignant diseases. This study aimed to evaluate the relationship between disease activity parameters and markers predicting lymphoma development in patients with PSS and 14-3-3η proteins. METHODS: This study was designed as an analytical case-control study. A total of 57 PSS patients and 54 healthy volunteers were included in the study. The European League Against Rheumatism (EULAR) Sjögren syndrome disease activity index (ESSDAI) was used to assess systemic disease activity in PSS. Receiver operating characteristic (ROC) analysis was used to test the diagnostic accuracy measures of the analytical results. Multivariable linear regression analysis was used to evaluate the effects of independent variables on the 14-3-3η protein. RESULTS: The 14-3-3η protein serum levels were found to be significantly higher in PSS (2.72 [2.04-4.07]) than healthy controls (1.73 [1.41-2.43]) (P<0.0001). A significant relationship was found between 14-3-3η protein levels and ESSDAI group (ß=0.385, 95%CI=0.318-1.651, P=0.005), hypocomplementemia (C3 or C4) (ß=0.223, 95% CI=0.09-1.983, P=0.048) and purpura (ß=0.252, 95% CI=0.335-4.903, P=0.022), which are accepted as lymphoma predictors. A significant correlation was found between PSS disease activity score ESSDAI and 14-33η protein (ß=0.496, 95% CI=0.079-0.244, P=0.0002). CONCLUSION: 14-3-3η proteins are potential candidates for diagnostic marker, marker of disease activity, and predictor of lymphoma in PSS patients.