The Association of Serum RANKL Levels with disease activity and Hematological Parameters in Syrian Patients with Rheumatoid Arthritis

doi:10.21203/rs.3.rs-1609896/v1

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The Association of Serum RANKL Levels with disease activity and Hematological Parameters in Syrian Patients with Rheumatoid Arthritis

https://doi.org/10.21203/rs.3.rs-1609896/v1

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published 22 Oct, 2022

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Our study aims to detect whether the serum RANKL could be a novel potential biomarker for activity and diagnosis of rheumatoid arthritis (RA). It included fifty-eight of RA patients and thirty of equal age and sex matched controls. Disease activity was determined by using DAS28-ESR. Serum Levels of RANKL were assayed by ELISA and compared with parameters such as ESR, CRP, Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). The serum RANKL levels were higher in RA patients compared to controls. There was an increase in its levels mean among post-menopausal patients compared to post-menopausal healthy group. RANKL levels were also higher in ACPA positive patients than ACPA negative. Our study found a correlation between RANKL levels and some parameters: DAS28, ACPA and symptom duration. No correlation was observed with ESR, TJC, SJC, RF, VAS, CRP. There was a moderate inverse correlation between RANKL levels and BMD. By ROC curve, our results displayed that the best cutoff value of serum RANKL was 178.99 pg/ml (sensitivity 79.31%; specificity 90%) to differentiate between RA patients and controls. In conclusion, elevated serum RANKL can be used as an indicator of disease activity and a diagnostic new biomarker in patients with early RA.

Rheumatoid Arthritis

RANKL

Disease activity

Parameters.

Table 1: Description of the study variables in RA patients’ group

Variables	Mean ± SD	Range (min, max)
Age (years)	48.71 ± 10.45	43 (24 - 67)
TJC	9.66 ± 4.56	18 (2 - 20)
SJC	5.43 ± 2.60	12 (0 - 12)
DAS28-ESR	5.39 ± 0.98	4.23 (7.4 - 3.17)
ESR (mm/h)	44.79 ± 16.62	65 (10- 75)
CRP (mg/L)	20.55 ± 22.66	105.8 (0.2 - 106)
VAS (%)	0.67 ± 0.20	0.80 (0.2 - 1.0)
(g/dl) Hb	11.94 ± 1.18	6.1 (8.9 -15)
WBC (x10³/mm³)	8.11 ± 2.09	9.3 (3.5 - 12.8)
Calcium (mg/dl)	8.88 ± 0.74	3.9 (6.10- 10)
RF (IU/L)	121.47 ± 133.78	706 (4 - 710)
Anti-CCP (U/L)	375.02 ± 345.75	1316.5 (3.50 - 1320.0)
Symptom’s duration (months)	8.05 ± 3.63	13 (3 - 16)
TJC: tender joint count, SJC: swollen joint count, ESR: Erythrocyte sedimentation rate, DAS28: Disease activity score in 28 joints, CRP: C-reactive protein, VAS: visual analog scale, Hb: hemoglobin, WBC: white blood cell, RF: rheumatoid factor (RF), Anti-CCP: anti-cyclic citrullinated peptide.

Table 2: Comparison between the two study groups of RA patients in terms of sex, age and menopause

Variable	RA patients group (N=58)	Control group (N=30)	Chi-Square Tests (P-value)
Sex			0.630
Male	11 (19%)	7 (23.3%)
Female	47 (81%)	23 (76.7%)
Age categories			0.491
Less than 40	9 (15.5%)	6 (20%)
Between 40-49 years	22 (37.9%)	14 (46.7%)
50 and above	27 (46.6%)	10 (33.3%)
Menopause			0.132
Pre-menopause	31 (65%)	18 (78.3%)
Post-menopause	16 (35%)	5 (21.7%)
Variable	Mean ± SD	Mean ± SD	Mean Diff (95% CI)	Students t-test (P)
Age (years)	48.71 ± 10.45	46.17±10.94	2.54 (-2.2-7.3)	0.290

Table 3: Distribution of the RA patients according to DAS28-ESR

DAS28 ESR	N (%)	Mean ± SD
Low	2 (3.4%)	3.19 ± 0.02
Moderate	22 (37.9%)	4.63 ± 0.48
High	34 (58.6%)	6.003 ± 0.66

Table 4: Comparison of serum RANKL between RA patients and control according to menopause.

Serum RANKL Levels (pg/ml)	RA group Postmenopausal N= 16	Control group Postmenopausal N= 5	Mann-Whitney Test P
	Mean ± SD	Mean ± SD	0.002
	240.89 ± 159.73	148.31 ± 14.63
	Median	Median
	201.21	145.02

Table 5: The difference of RANKL levels in RA patients group according to DAS28

Variable	RANKL Levels (pg/ml)		Kruskal-Wallis Test P
DAS28 ESR	Mean ± SD	Median	Kruskal-Wallis Test P
Low (n = 2)	207.75 ± 38.7	207.75	0.963
Moderate (n = 22)	258.16 ± 158.73	205.14
High (n = 34)	243.65 ± 101.66	219.19

Table 6: Comparison of serum RANKL in RA patients according to RF antibodies

	RA patients (RF Neg) N= 10	RA Patients (RF Pos) N= 48	Mann-Whitney Test P
Serum RANKL Levels (pg/ml)	Mean ± SD	Mean ± SD	0.673
	217.57 ± 32.72	254.24 ± 135.05
	Median	Median
	226.16	206.75

Table 7: The correlation between RANKL levels and study variables

Serum RANKL Levels (pg/ml)
Variables	Spearman's rho	Spearman's rho P
ESR	0.161	0.227
CRP	0.258	0.050
RF	0.086	0.522
Anti-CCP	0.320	0.04
TJC	0.215	0.105
SJS	0.074	0.580
VAS	0.157	0.238
DAS28	0.4	0.04
Symptom’s duration	0.346	0.008
Lumbar spine BMD (g/cm²)	-0.439	0.005
Femoral neck BMD (g/cm²)	-0.406	0.007

Table 8: AUC according to state group and the negative actual state group

Test Result Variable(s): RANKL levels (pg/ml)
Area under curve	Std. Error^a	Asymptotic Sig.^b	Asymptotic 95% Confidence Interval
			Lower Bound	Upper Bound
.902	.031	.000	.841	.962
The test result variable(s): RANKL has at least one tie between the positive actual state group and the negative actual state group. Statistics may be biased. a. Under the nonparametric assumption b. Null hypothesis: true area = 0.5

Table 9: Sensitivity, specificity and Intersection table for the distribution of RA patients and control group according to positive or negative of serum RANKL.

	RA group (N=58)	Control group (N=30)	All participants	Chi Square P-value
Positive (RANKL)	46	3	49	0.000
Negative (RANKL)	12	27	39
	58	30	88
Cut-Off: 178.99 Sensitivity: 79.31% Specificity: 90% Positive Predictive value (PPV):93.88% Negative Predictive value (NPV): 69.23% Odd Ratio (OR) Value & 95% CI & P-value: 34.50, (8.9 to 133.3), P < 0.000

No competing interests reported.

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The Association of Serum RANKL Levels with disease activity and Hematological Parameters in Syrian Patients with Rheumatoid Arthritis

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