14-3-3 Eta protein as a novel biomarker in early detection of uveitis in Egyptian juvenile idiopathic arthritis and rheumatoid arthritis patients: Diagnostic and prognostic value

Introduction

Juvenile Idiopathic Arthritis (JIA) is considered the most common heterogeneous group of arthritis of unknown etiology beginning in the pediatric population before sixteen years of age and lasting for more than six weeks.^[1] JIA is a major cause of acquired impairment and significant handicapping in children and adolescents because of aggressive joint involvement in adult life in many JIA patients. About 1–3 per 1000 children are affected by JIA worldwide.^[1]

Up till now, JIA diagnosis has been difficult as being represented with inflammatory arthritis with no specific accurate test to confirm the diagnosis.^[2] There is a classification system for JIA by the International League Against Rheumatism (ILAR) however, it doesn’t make an accurate diagnosis and hasn’t any specific biomarkers except for rheumatoid factor (RF), anti-cyclic citrullinated peptide (Anti-CCP) antibodies, and antinuclear antibody (ANA).^[3] So, a specific biomarker for JIA can prevent its diagnostic delay and complications, improving the outcomes.

About 1% of people worldwide suffer from rheumatoid arthritis (RA), a chronic inflammatory autoimmune illness with no known cause that strikes women two to three times more commonly than it does in males.^[4] Even though RA affects both small and big joints, symmetric extra-articular symptoms are frequently seen, particularly in cases where therapy is postponed. The eye may be impacted by necrotizing vasculitis of the small and medium-sized arteries, which in turn can also damage multiple organs.^[4] In rheumatoid arthritis, the eye is a common extra-articular source of inflammation. These conditions can range from benign ones like keratoconjunctivitis sicca and episcleritis to potentially vision-threatening ones like scleritis and peripheral ulcerative keratitis as well as potentially life-threatening problems. To effectively treat these individuals, ophthalmology and rheumatology should collaborate.^[5]

All eukaryotic cells have internal chaperonins known as 14-3-3 Eta proteins. The human 14-3-3 isoforms are β, γ, ε, η, σ, τ/θ, and ζ (Beta, Gamma, Epsilon, Eta, Sigma, Tau/Theta, and Zeta), each having a unique name. They play a vital part in several intracellular biological processes, such as apoptosis, differentiation, and cell division.^[6,7]

The 14-3-3 Eta protein functions as an inducer of the innate immune system when released into the extracellular space during the early phases of JIA and RA. Additionally, patients with arthritis have higher serum 14-3-3 Eta protein levels inducing the production of proinflammatory cytokines like tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-1β, which can lead to joint degradation including matrix metalloproteinase 9 and receptor activator of nuclear factor-κB ligand (RANKL).^[6] Thus, 14-3-3 Eta protein may enhance laboratory effectiveness in the early diagnosis and prognosis of RA and JIA.^[8,9]

The uveitis is one of the commonest and most dangerous extra-articular manifestations of JIA and RA especially in the oligoarthritic subtype presenting with chronic anterior uveitis with also non-specific biomarkers for its early detection.^[5,10] As 14-3-3 Eta protein is a proinflammatory cytokine inducer, it may therefore be a prospective and useful diagnostic tool for evaluating JIA and RA patients at risk of uveitis. Although the importance of 14-3-3 Eta proteins in several rheumatic diseases has been evaluated, its significance in the early identification of uveitis linked to JIA and RA is still being debate.^[2,11] In this study, serum 14-3-3 Eta protein was compared to other biomarkers, such as RF and Anti-CCP, to assess its potential as a novel biomarker for the early diagnosis of uveitis in Egyptian patients with JIA and RA, as well as its correlation with disease activity, was conducted.

Patients and Methods

Results

Availability of the Data

The article incorporates the data used to substantiate the outcomes of this investigation.

A case-control study was conducted on 84 patients with JIA, and RA was divided into two groups equally, with 42 patients in each group.

Table 1 shows the demographic data among the two patient groups, there was a female predominance in both groups as there was 71.4% in the JIA group, and 85.7% in the RA group. The mean age in JIA group was 12.17 ± 3.36, versus 46.27 ± 6.44 in RA group, mean disease duration was 2.81 ± 0.86 in JIA group versus 7.12 ± 2.39 in RA group, the mean serum level of Eta protein was 29.52 ± 34.68 in JIA group versus 38.90 ± 33.41 in RA group, the mean of TJC, SJC, patient global assessment (PGA), and physical global assessment (PhGA) among JIA group were 4.67 ± 2.06, 2.79 ± 2.13, 5.43 ± 1.50, and 6.00 ± 1.53 respectively versus 2.88 ± 3.25, 1.46 ± 2.55, 5.02 ± 2.35, and 5.12 ± 1.82 in RA group, mean ESR, CRP, health assessment questionnaire (HAQ), was 40.12 ± 31.01, 13.05 ± 12.44, 1.57 ± 0.80 respectively, versus 28.73 ± 31.13, 11.02 ± 12.00, 1.73 ± 1.05 in RA group. The mean ANA was 1.97 ± 1.74 in JIA group versus3.38 ± 2.86 in RA group respectively with significant (P = 0.019, Table 1).

Table 1

Demographic data among the two patients’ groups.

Variable	JIA (n = 42)		RA (n = 42)		P value
	No.	%	No.	%
Sex
Male	12	28.6	6	14.3	0.111
Female	30	71.4	36	85.7
Age (Years)	12.17 ± 3.36		46.27 ± 6.44		<0.001*
BMI (kg/m2)	17.21 ± 1.46		29.63 ± 3.09		<0.001*
Disease duration
(Years)	2.81 ± 0.86		7.12 ± 2.39		<0.001*
Eta (μg/L)	29.52 ± 34.68		38.90 ± 33.41		0.027*
TJC	4.67 ± 2.06		2.88 ± 3.25		<0.001*
SJC	2.79 ± 2.13		1.46 ± 2.55		<0.001*
PGA	6.00 ± 1.53		5.02 ± 2.35		0.002*
PhGA	5.43 ± 1.50		5.12 ± 1.82		0.353
DAS28	----		3.69 ± 1.77		----
JDAS	16.25 ± 7.28		----		----
ESR	40.12 ± 31.01		28.73 ± 31.13		0.001*
CRP	13.05 ± 12.44		11.02 ± 12.00		0.029*
ANA	1.97 ± 1.74		3.38 ± 2.86		0.019*
HAQ	1.57 ± 0.80		1.73 ± 1.05		0.458
Severity
Remission	0	0	16	38.1	<0.001*
Low	28	66.7	0	0
Mild	0	0	10	23.8
Moderate	6	14.3	6	14.3
High	8	19	10	23.8
RF
Positive	23	54.8	33	78.6	0.021*
Negative	19	45.2	9	21.4
Subtypes
Polyarthritis	23	54.8	----	----	----
Oligo-arthritis	15	35.7
Enthesitis	4	9.5
Dry eye	11	26.2	15	35.7	0.345
Uveitis	8	19	4	9.4	0.212
Complications
Present	1	2.4	3	7.1	0.616
Absent	41	97.6	39	92.9

1. *, statistically significant; χ², Chi-squared test; t, Student t test; U: Mann-Whitney U test; ANA, antinuclear antibody; FE, Fisher exact test; n = number; JIA, juvenile idiopathic arthritis; RA, rheumatoid arthritis; BMI, body mass index; TJC, tender joint count; SJC, swollen joint count; PGA, patient global assessment; PhGA, physical global assessment; DAS28, disease activity score; JADAS, juvenile arthritis disease activity scales; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; HAQ, health assessment questionnaire; RF, rheumatoid factor; NA, antinuclear antibody.

The mean of DAS28 was 3.69 ± 1.77 in the RA patients’ group, and the mean JADAS was 16.25 ± 7.28 in the JIA group. Among the JIA patients’ group, about 54.8% of them had polyarthritis, while about 35.7% and 9.5% had oligoarthritis, and enthesitis, 26.2% of them had dry eye versus 35.7% in the RA group, 19% had uveitis versus 9.4% in RA group, and the eye complications were found among 2.4 of them versus 7.1% in RA group. Among the JIA patients’ group, about 54.8% were RF positive, versus 78.6% in RA patients’ group (Table 1).

There was a significant statistical deference among JIA patients’ group and controls regarding the serum level of 14-33 Eta protein (P < 0.001), with also a statistically significant deference found among RA patients’ group versus controls regarding the serum level of 14-3-3 Eta protein (P < 0.001, Table 2).

Table 2

Comparison between cases and control regarding Eta level

Variable	Cases (n = 42)	Control (n = 42)	Test of significance	P value
JIA
Eta (μg/L)
Mean ± SD	29.52 ± 34.68	6.46 ± 5.04	U = 6.82	< 0.001
Range	8-130	1-23
RA
Eta (μg/L)
Mean ± SD	38.36 ± 33.19	10.67 ± 2.87	U = 6.70	< 0.001*
Range	10-115	6-20

1. *, statistically significant; U, Mann-Whitney U test; n, number; JIA, juvenile idiopathic arthritis; RA, rheumatoid arthritis.

There was a significant indirect relationship between age, and body mass index (BMI) with serum level of 14-3-3 Eta protein in the JIA patients’ group, while a significant direct relationship between serum level of 14-3-3 Eta protein and disease duration, TJC, SJC, PGA, PhGA, JADAS28, ESR, CRP, and HAQ was observed (Table 3).

Table 3

Correlation between Eta and other parameters among juvenile arthritis and rheumatoid arthritis studied patients

Parameter	JIA		RA
	Eta (μg/L)		Eta (μg/L)
	rho	P-value	rho	P-value
Age (Years)	-0.416	0.006*	0.089	0.576
BMI (kg/m2)	-0.409	0.007*	-0.118	0.458
Disease duration (Years)	0.068	0.668	0.021	0.897
TJC	0.618	<0.001*	0.773	<0.001*
SJC	0.701	<0.001*	0.766	<0.001*
PGA	0.658	<0.001*	0.853	<0.001*
PhGA	0.672	<0.001*	0.760	<0.001*
DAS28	----	----	0.842	<0.001*
JDAS	0.959	<0.001*	--	---
ESR	0.796	<0.001*	0.642	<0.001*
CRP	0.692	<0.001*	0.662	<0.001*
ANA	0.917	<0.001*	0.824	<0.001*
HAQ	0.787	<0.001*	0.806	<0.001*

1. *, statistically significant; rho, correlation coefficient; JIA, juvenile idiopathic arthritis; RA, rheumatoid arthritis; BMI, body mass index; TJC, tender joint count; SJC, swollen joint count; PGA, patient global assessment; PhGA, physical global assessment; DAS28, disease activity score; JADAS, juvenile arthritis disease activity scales; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; HAQ, health assessment questionnaire; ANA, anti-nuclear antibody.

There was a statistically significant positive correlation between 14-3-3 protein Eta and ANA in the JIA patient group (P < 0.001, Table 3).

A direct relationship between serum level 14-3-3 protein Eta and age, disease duration, TJC, SJC, PGA, PHGA, DAS28, ESR, CRP, and HAQ was observed in RA patients’ group with indirect relationship between it and BMI (Table 3).

The diagnostic accuracy of the 14-3-3 protein Eta biomarker in the prediction of RA disease occurrence in patients versus controls was at a cut-off point of 14.5 μg/L, AUC of 0.924, 95% CI = 0.868–0.980, while its diagnostic accuracy in JIA patients was at an 8.5 μg/L cut off point, and AUC of 0.930 (95% CI = 0.875–0.985, Table 4).

Table 4

Diagnostic accuracy of Eta in prediction of disease

Diagnostic accuracy	JIA	RA
AUC	0.930	0.924
P value	<0.001*	<0.001*
95% CI	0.875-0.985	0.868-0.980
Cut off point	8.5	14.5
Sensitivity	98%	83%
Specificity	81%	90%
Accuracy	89%	87%
PPV	84%	90%
NPV	97%	84%

1. *, statistically significant; AUC, area under curve; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value; JIA, juvenile idiopathic arthritis; RA, rheumatoid arthritis.

The diagnostic accuracy of 14-3-3 protein Eta in the prediction of uveitis in RA patients was a cut-off point of 57.5, with AUC = 0.992, 100% sensitivity, 97% specificity, 98% accuracy, 0.637–0.969 95% CI, 91% positive predictive value (PPV), and 100% negative predictive value (NPV), while its diagnostic accuracy at a cut-off point 12.75 in JIA patients, with low sensitivity 63%, specificity, 62%, and accuracy62% to differentiate between cases with or without uveitis, PPV was 28%, NPV was 88%, with a 0.530 AUC (Table 5).

Figure 1

A, ROC curve for Eta as a predictor for JIA; B, ROC curve for Eta as a predictor for RA; C, ROC curve of Eta as a predictor of uveitis in JIA; D, ROC curve of Eta as a predictor of uveitis in RA. RA, rheumatoid arthritis; JIA, juvenile idiopathic arthritis.

Table 5

Diagnostic accuracy of Eta in prediction of uveitis

Diagnostic accuracy	JIA	RA
AUC	0.530	0.992
P-value	0.784	<0.001*
95% CI	0.282-0.777	0.972-1.000
Cut off point	12.75	57.5
Sensitivity	63%	100%
Specificity	62%	97%
Accuracy	62%	98%
PPV	28%	91%
NPV	88%	100%

1. *, statistically significant; AUC: area under curve; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value; JIA, juvenile idiopathic arthritis; RA, rheumatoid arthritis.

Analysis of each subtype of JIA showed elevated levels of 14-3-3 protein Eta in enthesitis, oligoarthritis and polyarthritis subtypes of JIA with the highest levels in the polyarthritis JIA group (17.25 ± 6.29, 13.70 ± 4.70, and 41.98 ± 43.14 respectively, Table 6).

Table 6

Subtypes of juvenile arthritis studied patients in relation to different clinical and laboratory parameters

Variable	JIA (n = 42)			P value
	Enthesitis (n = 4)	Oligoarthritis (n = 15)	Polyarthritis (n = 23)
Eta (μg/L
Mean ± SD	17.25 ± 6.29	13.70 ± 4.70	41.98 ± 43.14	0.020*
Range	10-23	9-25	8-130
ESR
Mean ± SD	26.25 ± 6.29	27.33 ± 12.66	50.87 ± 37.65	0.184
Range	20-35	10-50	10-125
CRP
Mean ± SD	5.75 ± 0.50	9.47 ± 5.19	16.65 ± 15.46	0.084
Range	5-6	4-24	4-48
ANA
Mean ± SD	1.25 ± 0.58	1.10 ± 0.70	2.67 ± 2.04	0.044*
Range	0.8-2.1	0.5-2.9	0.6-6.5
Uveitis
Present	0 (0 %)	0 (0 %)	8 (%34.8)	0.017
Absent	4 (100 %)	15 (100 %)	15 (65.2%)

1. *, statistically significant; K, Kruskal Wallis test; χ², Chi-squared test; JIA, juvenile idiopathic arthritis; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; ANA, anti-nuclear antibody.

There was statistically significant difference between enthesitis, oligoarthritis and polyarthritis subtypes of JIA and ANA with the highest level of ANA observed in the polyarthritis JIA group (P = 0.044, Table 6).

Regarding uveitis, no patients in the enthesitis or the oligoarthritis group had uveitis while eight patients in the polyarthritis group had uveitis (P = 0.017, Table 6).

Discussion

Rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are chronic inflammatory autoimmune illnesses with unclear causes, there is a considerable chance of major consequences, such as irreversible visual loss, if related uveitis develops in those patients. Consequently, it is crucial to screen at-risk patients for JIA, and RA-associated uveitis.^[17,18]

In JIA patients, ANA is linked to uveitis, which if left undetected and untreated, could result in irreversible vision loss. To be clinically reliable, ANA testing is neither sensitive nor a specific predictor of uveitis risk, and it is unclear which characteristic autoantigens in JIA are specifically targeted by ANA. It is essential to discover particular autoantibodies that are highly correlated with uveitis since these can serve as biomarkers to help identify JIA patients who are at risk.^[19]

One RA biomarker that is quite specific is the 14-3-3 Eta protein. In addition to providing a 15% additive advantage to the diagnostic sensitivity of the markers, RF, and CCP antibodies, it has predictive utility in identifying patients with early RA.^[9,20]

Due to its correlation with the positivity of RF and anti-CCP in early JIA, previous studies have reported the role of serum 14-3-3 Eta protein in the early diagnosis of JIA especially the polyarthritis JIA group. Other studies have also shown the role of 14-3-3 Eta in determining the validity of the diagnosis of RA and the severity of early rheumatoid arthritis.^[9,18,21]

Nevertheless, there is currently no proof estimating the effectiveness of the 14-3-3 Eta protein biomarker in JIA patients, either in identifying the disease’s activity or its role in identifying uveitis risk in JIA, and RA patients. Thus, in Egyptian JIA and RA patients, this is the first study to evaluate the relevance of blood 14-3-3 Eta protein as a possible novel biomarker for early uveitis identification.

The present study revealed the female predominance in JIA, and RA patients, as there were about 71.4%, and 85.7% of the studied patients among the two groups respectively, with seropositivity in about 54.8% of JIA patients, and 78.6% of RA patients. That agreed with previous studies that reported female predominance among 66.6%, 78%, and 85% respectively.^[21,22,23] Our findings reported a significant positive correlation between ANA and serum14-3-3 Eta protein in JIA patients, especially the polyarticular juvenile idiopathic arthritis (PJIA). Based on our search, there are few studies comparing the prevalence of positive ANA and serum 14-3-3 Eta protein. The study by Storwick et al., reported significant prevalence of ANA in JIA patients, stating that 30%–50% of JIA patients had positive ANA in varying percentages among the JIA subtypes which comes in agreement with our data.^[24]

The study by Reyhan et al. comes in contrast to our findings reporting no association between positive ANA and 14-3-3 Eta. Overall, 60% of PJIA RF+ patients with positive ANA had serum 14-3-3 Eta levels above baseline. There was no association between positive ANA and 14-3-3 Eta among all groups (P = 0.119, OR = 1.96).^[21]

According to the study by Risha et al.^[2], which included fifty JIA patients who met the ILAR classification criteria, there were statistically significant differences between the JIA and RA patient groups and the control group regarding the level of 14-3-3 Eta (μg/L)(P < 0.001). The study also found that JIA patients had significantly more serum 14-3-3 Eta proteins (27.7 μg/L) than healthy individuals (0.9 μg/L)(P < 0.05), and that these differences were positively correlated with RF and Anti-CCP especially in the polyarthritis JIA group.

Our findings are supported by Jianxin et al., which found that RA patients had considerably higher levels of 14-3-3 Eta expression. Receiver operating characteristic (ROC) analysis also suggested that this gene could be used as a predictive marker for RA risk. Serum levels of 14-3-3 Eta were positively linked in RA patients with erythrocyte sedimentation rate (P = 0.006), disease activity score in 28 joints (P = 0.025), and illness duration (P = 0.003).^[25]

Also, the study by Abdelhafiz et al. comes in agreement with our findings estimating the role 14-3-3 Eta protein in RA which has now got adequate evidence for helping in assessing the veracity of the diagnosis and severity of early RA.^[9]

Regarding the 14-3-3 Eta (μg/L) level, our study revealed statistically significant differences between JIA subtypes being detected in all subtypes of JIA group but most common and highest in the polyarthritis group. Several researches showed statistically significant differences between the groups of RA patients, JIA patients, and the control group.^{[20,21,26,27]}

The current study reported a positive relationship between 14-3-3 Eta with clinical and laboratory indicators of disease activity, disease duration in JIA (P = 0.668), and RA (P = 0.897), CHAQ, and RF in both patients’ groups. Risha et al. documented the significant positive correlation between serum 14-3-3 Eta proteins in JIA patients and RF, Anti-CCP (P = 0.034 and 0.040, respectively), and CHAQ (P = 0.026) with no significant correlation with juvenile arthritis disease activity score 27 (JADAS27) score (P = 0.303).^[2] Serum levels of 14-3-3 Eta were shown to be favorably correlated with erythrocyte sedimentation rate (P = 0.006), disease activity score in 28 joints (P = 0.025), and illness duration (P = 0.003) in patients with RA, according to Jianxin et al.^[25]

Also, several studies that documented the positive association between 14-3-3 Eta protein with laboratory markers of disease activity, and functional outcomes regarding CHAQ, reported the positive relationship between acute phase reactants (ESR & CRP), RF, clinical parameters regarding DAS28, number of swollen joints with 14-3-3 Eta level RA _patients.[2,9,23,26]

The 14-3-3 Eta level and RF had a statistically significant (P < 0.05) association. Whereby 14-3-3 Eta levels are greater in positive RF with respect to adult RA patients and JIA with the highest level in the polyarthritis group as compared to the enthesitis and oligoarthritis group. Compared to seronegative cases, the serum 14-3-3 Eta level was greater in adult RA (44.00 ± 35.31) and seropositive JIA (40.24 ± 43.17). These outcomes are comparable to those of JIA cases found by Risha et al.^[2]

In contrast to our results, there was a study by Reyhan et al. and Risha et al. reported no significant association between age and disease activity using JADAS and 14-3-3 Eta level in JIA patients upon diagnosis.^[2,21]

The diagnostic accuracy of the 14-3-3 Eta protein biomarker in prediction of RA disease occurrence in patients of the present study versus controls was at a cut-off point 14.5 μg/L, with AUC of 0.924, and 95% CI = 0.868–0.980, while its diagnostic accuracy in JIA patients was at an 8.5 μg/L cut off point, and AUC of 0.930 (95% CI = 0.875–0.985). The data from Wang et al. support our findings, which show that 14-3-3 Eta protein functions as a sensitive and specific biomarker for RA, with an area under the curve of 0.9245 and a pooled sensitivity and specificity of 0.73 (95% CI: 0.71–0.75) .^[28] In reference to JIA Risha et al. revealed that the serum 14-3-3 Eta protein RO) has been found to have 84% sensitivity, 55% specificity, 65.6% PPV, and 69.2% NPV among all JIA subgroup patients at levels greater than 1.45 μg/L ^[2]

Numerous studies reported different cutoff points for 14-3-3 Eta protein among RA, JIA patients versus controls, this wide variations in the cut-off value in these studies may be related to the differences in ethnicity, disease duration, activity, and the biomarker reading range.^[27,29]

Our study showed the prevalence of uveitis among the polyarticular subtype of JIA patients, being present in 8 (% 34.8) of 23 patients. The study by Qian et al., comes in agreement with our findings reporting the prevalence of uveitis in polyarticular JIA subtype.^[30] Also, the study by Reyhan et al. showed that 12 (33%) of the 36 polyarticular juvenile idiopathic arthritis (OJIA) patients had chronic uveitis which is consistent with our findings.^[21]

In contrast to our study, the study by Heiligenh et al. which detected that uveitis is more common in the oligoarthritis subtype of JIA and rheumatoid factor–positive polyarthritis are rarely ( < 1%) accompanied by uveitis.^[31]

The diagnostic accuracy of 14-3-3 Eta in prediction of uveitis in RA patients was at a cutoff point of 57.5, with 0.992 of AUC, 100% sensitivity, 97% specificity, 98% accuracy, 0.637–0.969 95% CI, 91% PPV, and 100% NPV, while its diagnostic accuracy at a cut-off point 12.75 in JIA patients, with low sensitivity 63%, specificity, 62%, and accuracy 62% to differentiate between cases with or without uveitis, PPV was 28%, NPV was 88%, with a 0.530 AUC.

Reyhan et al. study which shows that 12 (33%) of the 36 PJIA patients had chronic uveitis, is consistent with our findings. In polyarticular patients with 14-3-3 Eta (9/28; 33%), uveitis was as common as in those without 14-3-3 Eta (3/8; 38%), even though the numbers were too small for statistical analysis. Consistent with our findings, 14-3-3 Eta was not found in uveitis patients in other JIA groups.^[21]

To the best of our knowledge, this study is the first to highlight and explore the role of 14-3-3 Eta protein biomarker in the early detection of uveitis among RA patients with a highly sensitive, specific, and accurate cutoff point, as, at 14-3-3 Eta protein biomarker serum level of 57.5, we could predict the occurrence of uveitis, and patients must be screened with a thorough ophthalmologic investigation at this cut-off point.

Limitations of the Study

There are a few restrictions on the current study, one of which is the very small sample size. To prove the validity and dependability of our findings, more study with larger sample numbers is therefore necessary. Future research should hopefully concentrate more on the therapeutic effects of the sensitive biomarker 14-3-3 Eta protein than on its potential uses in diagnosis.

Conclusion

14-3-3 Eta protein is a potential diagnostic biomarker in early detection of uveitis in RA patients, as it is higher in patients versus controls especially those with uveitis with a cut-off point 57.5, at which patients must have a thorough eye examination to receive early intervention and, to prevent complications, while it doesn’t have the same role in JIA patients. 14-3-3 Eta protein is a potential diagnostic and prognostic marker for JIA and RA being correlated with disease activity.