The Clinical Significance of Anticyclic Citrullinated Peptide Antibodies in Juvenile Rheumatoid Arthritis

Min Kang; Tae-Young Sohn; Sung-Hye Kim; Hae-Ran Lee; Hee-Jung Kang; Kwang-Nam Kim

doi:10.4078/jrd.2014.21.5.236

Journal List > J Rheum Dis > v.21(5) > 1064131

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Kang, Sohn, Kim, Lee, Kang, and Kim: The Clinical Significance of Anticyclic Citrullinated Peptide Antibodies in Juvenile Rheumatoid Arthritis

Original Article

J Rheum Dis 2014;21(5):236-240.

Published online: 31 October 2014

DOI: https://doi.org/10.4078/jrd.2014.21.5.236

The Clinical Significance of Anticyclic Citrullinated Peptide Antibodies in Juvenile Rheumatoid Arthritis

Min Kang¹, Tae-Young Sohn¹, Sung-Hye Kim¹, Hae-Ran Lee¹, Hee-Jung Kang², Kwang-Nam Kim¹

¹Department of Pediatric and Adolescent Medicine, College of Hallym University Sacred Heart Hospital, Anyang, Korea

²Department of Laboratory Medicine, College of Hallym University Sacred Heart Hospital, Anyang, Korea

Corresponding to: Kwang-Nam Kim, Department of Pediatrics, Hallym University Sacred Heart Hospital, 22, Gwanpyeong-ro, 170beon-gil, Dongan-gu, Anyang 431-796, Korea. E-mail: kwangnamkim@naver.com

Received 27 June 2014 Revised 28 August 2014 Accepted 28 August 2014

This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

The aim of this study was to determine the clinical significance of anti-cyclic citrullinated peptide (anti-CCP) antibody in juvenile rheumatoid arthritis (JRA).

Methods

Sera for anti-CCP assay were obtained from 142 patients with arthralgia in our hospital during the period between November 2010 and October 2011. On the basis of medical records, 83 patients with JRA were designated to the study group, and 59 patients with arthralgia but were treated as transient arthritis to the control group. The values of anti-CCP were then analyzed retrospectively. We used the enzyme linked immunosorbent assay (ELISA) for detecting anti-CCP.

Results

Positive anti-CCP values were found in the sera of 11 patients with JRA (13.3%), one patient presented with pauciarticular JRA and the others with polyarticular JRA. There was a statistically significant difference in the anti-CCP values between the JRA group and the control group. However, patients with systemic JRA and arthralgia without JRA had no anti-CCP. Especially, 10 out of 14 (71.4%) patients with RF-positive polyarticular JRA had anti-CCP. In addition, the rate of positive anti-CCP was significantly higher in patients with polyarticular JRA than in the control group.

Conclusion

We expect that the presence of anti-CCP may help to evaluate the severity of diseases in patients with JRA. Anti-CCP can be an important biomarker for making early intensive therapeutic decision in patients with polyarticular JRA, which might have more severe course and longer disease duration.

Keywords: Juvenile rheumatoid arthritis, Polyarticular, Cyclic citrullinated peptide

REFERENCES

1. Cassidy JT, Levinson JE, Bass JC, Baum J, Brewer EJ Jr, Fink CW, et al. A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis. Arthritis Rheum. 1986; 29:274–81.

2. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004; 31:390–2.

3. Woo P, Wedderburn LR. Juvenile chronic arthritis. Lancet. 1998; 351:969–73.

4. Goldbach-Mansky R, Lee J, McCoy A, Hoxworth J, Yarboro C, Smolen JS, et al. Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset. Arthritis Res. 2000; 2:236–43.

5. Schellekens GA, Visser H, de Jong BA, van den Hoogen FH, Hazes JM, Breedveld FC, et al. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum. 2000; 43:155–63.

6. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/ European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010; 62:2569–81.

7. Lawrence JM 3rd, Moore TL, Osborn TG, Nesher G, Madson KL, Kinsella MB. Autoantibody studies in juvenile rheumatoid arthritis. Semin Arthritis Rheum. 1993; 22:265–74.

8. Symmons DP, Jones M, Osborne J, Sills J, Southwood TR, Woo P. Pediatric rheumatology in the United Kingdom: data from the British Pediatric Rheumatology Group National Diagnostic Register. J Rheumatol. 1996; 23:1975–80.

9. Gedalia A, Molina JF, García CO, Doggett S, Espinoza LR, Gharavi AE. Anticardiolipin antibodies in childhood rheumatic disorders. Lupus. 1998; 7:551–3.

10. Serra CR, Rodrigues SH, Silva NP, Sztajnbok FR, Andrade LE. Clinical significance of anticardiolipin antibodies in juvenile idiopathic arthritis. Clin Exp Rheumatol. 1999; 17:375–80.

11. Avcin T, Cimaz R, Falcini F, Zulian F, Martini G, Simonini G, et al. Prevalence and clinical significance of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis. Ann Rheum Dis. 2002; 61:608–11.

12. Nesher G, Moore TL, Grisanti MW, el-Najdawi E, Osborn TG. Antiperinuclear factor in juvenile rheumatoid arthritis. Ann Rheum Dis. 1992; 51:350–2.

13. Gabay C, Prieur AM, Meyer O. Occurrence of antiperinuclear, antikeratin, and anti-RA 33 antibodies in juvenile chronic arthritis. Ann Rheum Dis. 1993; 52:785–9.

14. el-Gamal Y, Hossny E, Mabrouk R, el-Gamasey T. Antiperinuclear factor in the diagnosis of juvenile rheumatoid arthritis. Pediatr Allergy Immunol. 1995; 6:165–9.

15. Serra CR, Rodrigues SH, Sztajnbok FR, Silva NP, Andrade LE. Antiperinuclear factor and antibodies to the stratum corneum of rat esophagus in juvenile idiopathic arthritis. J Pediatr. 1999; 134:507–9.

16. Abreu I, Gomes JA. “Antikeratin antibodies” in chronic arthritis of childhood. Clin Exp Rheumatol. 1998; 16:516–7.

17. Hromadníková I, Vavrincova P, Stechova K, Hridelova D. Antikeratin antibodies in patients with juvenile idiopathic arthritis. Clin Exp Rheumatol. 2001; 19:470–3.

18. van Boekel MA, Vossenaar ER, van den Hoogen FH, van Venrooij WJ. Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthritis Res. 2002; 4:87–93.

19. Low JM, Chauhan AK, Kietz DA, Daud U, Pepmueller PH, Moore TL. Determination of anti-cyclic citrullinated peptide antibodies in the sera of patients with juvenile idiopathic arthritis. J Rheumatol. 2004; 31:1829–33.

20. Ferrell EG, Ponder LA, Minor LS, Angeles-Han ST, Kennedy CW, Rouster-Stevens KA, et al. Limitations in the classification of childhood-onset rheumatoid arthritis. J Rheumatol. 2014; 41:547–53.

21. van Rossum M, van Soesbergen R, de Kort S, ten Cate R, Zwinderman AH, de Jong B, et al. Anticyclic citrullinated peptide (anti-CCP) antibodies in children with juvenile idiopathic arthritis. J Rheumatol. 2003; 30:825–8.

22. Kasapçopur O, Altun S, Aslan M, Karaarslan S, Kamburoglu-Göksel A, Saribas S, et al. Diagnostic accuracy of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis. Ann Rheum Dis. 2004; 63:1687–9.

23. Kwok JS, Hui KH, Lee TL, Wong W, Lau YL, Wong RW, et al. Anticyclic citrullinated peptide: diagnostic and prognostic values in juvenile idiopathic arthritis and rheumatoid arthritis in a Chinese population. Scand J Rheumatol. 2005; 34:359–66.

24. Brunner J, Sitzmann FC. The diagnostic value of anti-cyclic citrullinated peptide (CCP) antibodies in children with Juvenile Idiopathic Arthritis. Clin Exp Rheumatol. 2006; 24:449–51.

25. Habib HM, Mosaad YM, Youssef HM. Anticyclic citrullinated peptide antibodies in patients with juvenile idiopathic arthritis. Immunol Invest. 2008; 37:849–57.

26. Kuna AT, Lamot L, Miler M, Harjacek M, Simundic AM, Vrkic N. Antibodies to mutated citrullinated vimentin and antibodies to cyclic citrullinated peptides in juvenile idiopathic arthritis. Clin Chem Lab Med. 2009; 47:1525–30.

27. Gupta R, Thabah MM, Vaidya B, Gupta S, Lodha R, Kabra SK. Anticyclic citrullinated peptide antibodies in juvenile idiopathic arthritis. Indian J Pediatr. 2010; 77:41–4.

28. Gilliam BE, Reed MR, Chauhan AK, Dehlendorf AB, Moore TL. Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2011; 9:8.

29. Tebo AE, Jaskowski T, Davis KW, Whiting A, Clifford B, Zeft A, et al. Profiling anti-cyclic citrullinated peptide antibodies in patients with juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2012; 10:29.

30. Cambridge G, Leandro MJ, Edwards JC, Ehrenstein MR, Salden M, Bodman-Smith M, et al. Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritis Rheum. 2003; 48:2146–54.

31. Ferucci ED, Majka DS, Parrish LA, Moroldo MB, Ryan M, Passo M, et al. Antibodies against cyclic citrullinated peptide are associated with HLA-DR4 in simplex and multiplex polyarticular-onset juvenile rheumatoid arthritis. Arthritis Rheum. 2005; 52:239–46.

32. Morbach H, Dannecker H, Kerkau T, Girschick HJ. Prevalence of antibodies against mutated citrullinated vimentin and cyclic citrullinated peptide in children with juvenile idiopathic arthritis. Clin Exp Rheumatol. 2010; 28:800.

Table 1.

Baseline characteristics of JRA and control

Characteristics	JRA (n=83)	Control (n=59)
Age (Mean± SD)	8.36±4.4	9.86±3.6
Sex
Male	42	30
Female	41	29

JRA: juvenile rheumatoid arthritis.

Table 2.

Comparison of anti-CCP values between patients with JRA and control

Characteristics		JRA (n=83) n %		Control (n=59) n %		p-value*
Characteristics		n	%	n	%	p-value*
JRA Diagnosis
Systemic JRA		11		59
Anti-CCP	(−)	11	100.0	59	100.0	1.00
	(＋)	0	0.0	0	0.0	1.00
Pauciarticular JRA		22		59
Anti-CCP	(−)	21	95.5	59	100.0	0.27
	(＋)	1	4.5	0	0.0	0.27
Polyarticular JRA		50		59
Anti-CCP	(−)	40	80.0	59	100.0	＜0.01
	(＋)	10	20.0	0	0.0	＜0.01
Total		83		59
Anti-CCP	(−)	72	86.7	59	100.0	＜0.01
	(＋)	11	13.3	0	0.0	＜0.01

JRA: juvenile rheumatoid arthritis, Anti-CCP: anti-cyclic citrullinated peptide.

^* Fisher's exact test.

Table 3.

Comparison of anti-CCP values between RF-positive and RF-negative polyarticular JRA

Serologicall tests		Polyarticuular JRA				p-value*
		RF-positive (n=14)		RF-neegative (n=36)
		n	%	n	%
Anti-CCP	(−)	4	28.6	36	100.0	＜0.01
	(＋)	10	71.4	0	0.0	＜0.01

JRA: juvenile rheumatoid arthritis, anti-CCP: anti-cyclic citrullinated peptide, RF: rheumatoid factor.

^* Fisher's exact test.

Table 4.

Summary of the published and present studies on anti-CCP in JRA

		JRA		RF-positive poly JRA		Control
Lead Author (Ref.)	Year	N	Prevalence of Anti-CCP antibody	N	Prevalence of Anti-CCP antibody	N	Prevalence of Anti-CCP antibody
Avcin T (11)	2002	109	1.8	1	0.0	30	0.0
Hromadnikova I (17)	2002	140	5.0	18	11.1	24	0.0
van Rossum M (21)	2003	71	14.1	11	72.7	0	−
Low JM (19)	2004	66	77.3	16	75.0	25	0.0
Kasapcopur O (22)	2004	122	2.5	12	25.0	15	0.0
Kwok JS (23)	2005	59	10.2	5	80.0	60	0.0
Ferucci ED (31)	2005	230	5.7	14	57.1	688	0.6
Brunner J (24)	2006	45	4.4	2	100.0	42	0.0
Habib HM (25)	2008	56	20.6	20	70.0	20	0.0
Kuna AT (26)	2009	68	1.8	2	50.0	17	0.0
Gupta R (27)	2010	78	23.1	8	87.5	0	−
Morbach H (32)	2010	191	2.6	6	66.7	88	1.1
Gilliam BE (28)	2011	96	14.6	16	56.3	10	−
Tebo AE (29)	2012	334	14.4	30	73.3	50	2.0
Present study	2014	83	13.3	14	71.4	59	0.0

JRA: juvenile rheumatoid arthritis. Anti-CCP: anti-cyclic citrullinated peptide. RF: rheumatoid factor.

TOOLS

Similar articles