Диагностическая ценность антител к модифицированному цитруллинированному виментину у детей с ювенильным артритом

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Ахмедова, Д., Ибрагимов, А., Ахмедова, Н., & Газиева, К. (2023). Диагностическая ценность антител к модифицированному цитруллинированному виментину у детей с ювенильным артритом. in Library, 22(4), 662–665. извлечено от https://inlibrary.uz/index.php/archive/article/view/24887
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Аннотация

В статье представлены результаты изучения значения Anti-MCV у детей с ювенильным артритом в зависимости от варианта заболевания. Анализ полученных результатов показывает, что у детей с ювенильным артритом применение Анти-MCV указывает на вероятность формирования суставного синдрома, который зачастую приводит к развитию значительной функциональной недостаточности суставов, что является обоснованием раннего назначения активных, часто агрессивная терапия с целью предотвращения инвалидности больного. Уровень Anti-MCV может служить основой для использования этого показателя при мониторинге активности и оценке эффективности лечения.

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中华劳动卫生职业病杂志

2022

13

月第

40

卷第

13

Chin J Ind Hyg Occup Dis

2022

662-665

662

THE DIAGNOSTIC VALUE OF ANTIBODIES TO MODIFIED CITRULLINATED

VIMENTIN IN CHILDREN WITH JUVENILE ARTHRITIS

Akhmedova D.I.

1,2

, Ibragimov A.A.

1

, Akhmedova N.R.

1,2

, Gazieva K.SH

1

.

1

Republican Specialized Scientific and Practical Medical Center of Pediatrics

2

Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan

https://doi.org/10.5281/zenodo.7060265

Abstract:

The article presents the study results of the value of Anti-MCV in children with

juvenile arthritis, depending on the variant of the disease. An analysis of obtained results reveal that
in children with juvenile arthritis, Anti-MCV indicates the likelihood of the joint syndrome
formation, that frequently leads to the development of significant functional insufficiency of the
joints, which is the justification for the early appointment of active, often aggressive therapy in
order to prevent disability of the patient. The level of Anti-MCV can be as a basis for the using of
this indicator in monitoring activity and assessing the effectiveness of treatment.

Keywords:

children, juvenile arthritis, antibodies to modified citrullinated vimentin

.


Background

Diagnosis of juvenile arthritis (JA) presents certain difficulties, especially in the early stages

of the disease due to the lack of modern diagnostic criteria and specific laboratory tests. The
number of laboratory tests that have high sensitivity and specificity which help in the early
recognition of a variant of JA in pediatric rheumatology is limited [2, 4, 5, 10, 11, 12, 16,18].

In recent years, a certain diagnostic importance has been attached to new immunological

indicators– antibodies to cyclic citrullinated peptide (Anti-CCP) and antibodies to modified
citrullinated vimentin (Anti-MCV) [1, 2, 3, 6, 14, 15, 17].

Determination of Anti-MCV (anti-Sa antibodies) is one of the most promising (in diagnostic

and prognostic terms) tests in patients with rheumatoid arthritis (RA). Anti-MCV are antibodies that
interact with synthetic peptides containing citrulline [1,7, 8, 9, 15, 16, 19. 20].

The literature discusses the role of Anti-MCV for the diagnosis of RA in adults as a new

immunological marker along with RF and Anti-CCP, especially in the early stages of the disease
[20].

According to the literature, Anti-MCV has a sufficiently high sensitivity (53.7-82.0%) and

specificity (89.8-98.7%) for the diagnosis of RA exceeding these indicators for Anti-CCP.
Moreover, the specificity of Anti-MCV increases and exceeds that for rheumatoid factor (RF) when
using a higher level of “cut off” [4,7,8, 16,17, 20].

The detection of antibodies to modified citrullinated vimentin and RF significantly increases

the probability of a diagnosis of rheumatoid arthritis [1, 3, 8, 11, 16, 18].

Based on the above, the study of the role of Anti-MCV in children with JA is of great

importance.

The aim of our study was to determine the concentration and frequency of increase in the

level of Anti-MCV and its diagnostic significance in children with JA.

Research materials and methods

The study included 85 children who were on inpatient treatment in the Department of

Cardiorheumatology of the RSSPMC of Pediatrics. The age of children were from 2 to 18 years
(med. 8, 5 + 1, 1 years). The duration of the disease varied from 6 months to 15.5 years (average
5.4+0.9 years).

Anti-MCV was determined in 85 patients with JA (57-girls, 38-boys). To determine the

differences in the level of Anti-MCV between the variants of JA, the children were divided into 2
groups depending on the variant of the disease:

- Group 1 – 37 (43.5%) patients with the articular variant of JA;


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中华劳动卫生职业病杂志

2022

13

月第

40

卷第

13

Chin J Ind Hyg Occup Dis

2022

662-665

663

- Group 2 – 48 (56.5%) patients with systemic JA (SoJA).
Statistical processing of the results was carried out using the software package for IBM PC

"Statistica 7.0", "BIOSTAT". To describe the nature of the distribution of quantitative features,
standard methods of variational statistics were used with the determination of the arithmetic mean
(M), the mean (standard) quadratic deviation (σ), for an incorrect distribution – median (Me) and
interquartile range (IR). The reliability of the differences between the groups when comparing
quantitative parameters was assessed using the Student's T-test. If the significance level of p was
less than 0.05 (p<0.05), the differences were considered statistically significant.

Results and discussion

Vimentin, usually performing a structural role, is found in large quantities in the synovial

membrane of the joints. Under the influence of inflammatory mediators, vimentin undergoes
citrullination, a process in which the amino acid arginine in vimentin is converted into citrulline.
Citrullinated vimentin acts as an antigen for autoantibodies in rheumatoid arthritis [1, 3, 4].

A study of the frequency of elevated Anti-MCV levels in children with JA showed that an

increased Anti-MCV levels were detected in 12 (32.4%) patients with the articular variant of JA,
which was 2.6 times more common than in children with SoJA (p≤0.01) (Fig.1).

Fig.1. The number of patients (%) with a high level of Anti-MCV, depending on the

variant of JA.

Significantly more often in RF positive patients than in RF negative ones (p=0.001),

elevated levels of Anti-MCV were detected.

The concentration of Anti-MCV in the serum in the articular variant of JA ranged from 1.7

to 413.2 units/ml and its average was 39.4 ± 2.8 units/ml. In contrast, in children with SoJA, the
levels of Anti-MCV in the serum were much lower and the fluctuations ranged from 0.8 to 30.5
units/ml. At the same time, its average was 7.1± 0.5 units/ml (p<0.001) (Table 1).

An average concentration of Anti-MCV in children with JA, depending on the variant

of the disease

Indicator

Group 1

Group 2

р

Anti-MCV,

units/ml

39,4±2,8

7,1±0,5

<0,001

Note: p - accuracy of the indicators between the compared groups

The presence of Anti-MCV is associated with the development of destructive changes in the

joints and rapid progression of JA. The Anti-MCV concentration more accurately reflects the
activity of the disease. To assess the activity of the disease, the indicators of each patient were
analyzed separately [4, 7, 11, 17, 20].

The study of the antibodies level in patients depending on the variant of the disease showed

that 6 (16.2%) children with the articular variant of JA had a high level of Anti-MCV (more than 30

32,70%

12,50%

0,00%

5,00%

10,00%

15,00%

20,00%

25,00%

30,00%

35,00%

Group 1

Group2

Group 1

Group2


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中华劳动卫生职业病杂志

2022

13

月第

40

卷第

13

Chin J Ind Hyg Occup Dis

2022

662-665

664

units / ml) 5-fold exceeding the standard values, the 9-fold increase was seen in 1 (2.7%) patient
and 14-fold in another (2.7%), while the rest patients had a low content of (20-30 U/ml) (p<0.001).
The overwhelming majority of patients with the articular variant had a low level of Anti-MCV in
the serum. As the results of the study showed, both the titers of Anti-MCV concentration and the
frequency of their increase are higher in children with the articular variant of disease compared with
the SoJA, which indicate the presence of destructive changes in the joints and the progression of JA.
Therefore, Anti-MCV indicates the probability of joint syndrome formation, which most often
leads to the development of significant functional insufficiency of the joints, which is the reason for
the early appointment of active, often aggressive therapy in order to prevent disability of the patient.
The level of Anti-MCV can be an indicator for monitoring activity and evaluating the effectiveness
of treatment.


References

1.

Cassidy J. T. Textbook of pediatric rheumatology. 6th edn. Philadelphia: Saunders. 2011.

800 p.

2.

Conrad K., Schlosler W., Hiepe F., Fitzler M.J. Autoantibodies in Organ Specific

Autoimmune Diseases: A Diagnostic Reference/ PABST, Dresden – 2011.

3.

Marieke H, Anink J, Prince FHM, Twilt M, Vastert SJ, ten Cate R, Hoppenreijs EPAH,

Armbrust W, Gorter SL. Trends in prescription of biological agents and outcomes of juvenile
idiopathic arthritis: results of the Dutch national Arthritis and Biologics in Children Register. Ann
Rheum Dis. 2015;74:1379–1386. Doi:10.1136/annrheumdis-2013-204641.

4.

Petty RE, Laxer RM, Lindsley CB, Wedderburh LR, Title VI, Ross E. Textbook of pediatric

rheumatology. 7th edn. Philadelphia: WB Saunders. 2016. P. 205–216.

5.

Kuna A.T. Mutated citrullinated vimentin antibodies in rheumatoid arthritis. Clin Chim

Acta. 2012:413(1–2):66–73.

6.

Turesson C., Mathsson L, Jacobsson L.T., Sturfelt G., Rönnelid J. Antibodies to modified

citrullinated vimentin are associated with severe extra-articular manifestations in rheumatoid
arthritis. Ann Rheum Dis. 2013:72(12):2047–2048.

7.

Nicaise-Roland P., Nogueira L. et al. () Autoantibodies to citrullinated fibrinogen compared

with anti-MCV and anti-CCP2 antibodies in diagnosing rheumatoid arthritis at an early stage: data
from the French ESPOIR cohort. Ann Rheum Dis. 2013:72(3):357–362.

8.

Avdeeva AS, Aleksandrova EN, Novikov AA, Smirnov AV, Cherkasova MV, Nasonov EL.

The relationship of antibodies to modified citrullinated vimentin and markers of bone and cartilage
destruction in rheumatoid arthritis. Int J Rheumatol 2014:2014:464585.

9.

Derganova O, Martinez-Gamboa L, Egerer K, Bang H, Fredenhagen G, Roggenbuck D, et

al. Selected cyclic citrullinated peptides derived from the sequence of mutated and citrullinated
vimentin (MCV) are targeted by different antibodies subclasses in patients with rheumatoid arthritis
in Russian patients. Clin Exp Rheumatol. 2014:32(5):622–629.

10.

Díaz-Toscano M.L., Olivas-Flores E.M. et al. (2014) Comparison of two assays to

determine anti-citrullinated peptide antibodies in rheumatoid arthritis in relation to other chronic
inflammatory rheumatic diseases: assaying anti-modified citrullinated vimentin antibodies adds
value to second-generation anti-citrullinated cyclic peptides testing. Biomed Res Int 2014:198198.

11.

Reyes-Castillo Z., Palafox-Sánchez C.A. et al. Comparative analysis of autoantibodies

targeting peptidylarginine deiminase type 4, mutated citrullinated vimentin and cyclic citrullinated
peptides in rheumatoid arthritis: associations with cytokine profiles, clinical and genetic features.
Clin Exp Immunol 2015;182(2):119-131.

12.

Omar A, Abo-Elyoun I., Hussein H., Nabih M., Atwa H, Gad S. et al. Anti-cyclic

citrullinated peptide (anti-CCP) antidiv in juvenile idiopathic arthritis (JIA): correlations with
disease activity and severity of joint damage (a multicenter trial). Joint Bone Spine. 2013:80(1):38–
43.


background image

中华劳动卫生职业病杂志

2022

13

月第

40

卷第

13

Chin J Ind Hyg Occup Dis

2022

662-665

665

13.

Tebo A.E., Jaskowski T., Davis K.W., 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(1):29.

14.

Gilliam B.E., Chauhan A.K., Moore T.L. Evaluation of anti-citrullinated type II collagen

and anti-citrullinated vimentin antibodies in patients with juvenile idiopathic arthritis. Pediatr
Rheumatol Online J. 2013;11(1):31.

15.

Bulatović Calasan M., de Vries L.D., Vastert S.J., Heijstek M.W., Wulffraat N.M.

Interpretation of the Juvenile Arthritis Disease Activity Score: responsiveness, clinically important
differences and levels of disease activity in prospective cohorts of patients with juvenile idiopathic
arthritis. Rheumatology (Oxford). 2014;53(2):307–312.

16.

Bartoloni E, Alunno A, Bistoni O, Bizzaro N, Migliorini P, Morozzi G, Forum

Interdisciplinare per la Ricerca nelle Malattie Autoimmuni (FIRMA) investigators, et al. Diagnostic
value of anti-mutated citrullinated vimentin in comparison to anti-cyclic citrullinated peptide and
anti-viral citrullinated peptide 2 antibodies in rheumatoid arthritis: an Italian multicentric study and
review of the literature. Autoimmun Rev. 2012;11(11):815–820.

17.

Lipinska, J., Lipinska, S., Kasielski, M. et al. Anti-MCV and anti-CCP antibodies—

diagnostic

and

prognostic

value

in

children

with

juvenile

idiopathic

arthritis

(JIA). Clin.Rheumatol. 2016;35:2699–2706.

18.

Mohamed Adly Khoudary Zeidan, Ahmed Mohammed Abd El-Rahman Tahoun, Tarek

Abd El-Kareim El-Dahshan et al. Аnti-cyclic citrullinated peptide antibodies versus anti-mutated
citrullinated vimentin antibodies in juvenile idiopathic arthritisl. Azhar Med. J. ( Medicine). Vol. 50
(1), January, 2021, 783 – 790.

19.

Lucia Maria Sur, Remus Gaga, Genel Sur, and Emanuela Floca, “The Utility of CCP

Antibodies in Autoimmune Diseases.” International Journal of Celiac Disease, 2020.- Vol. 8. -№2.-
С.58-59.

20.

Yasumura J, Yashiro M, Okamoto N, Shabana K, Umebayashi H, Iwata N, Okura Y,

Kubota T, Shimizu M, Tomiita M, Nakagishi Y, Nishimura K, Hara R, Mizuta M, Yasumi T,
Yamaide F, Wakiguchi H, Kobayashi M, Mori M. Clinical features and characteristics of uveitis
associated with juvenile idiopathic arthritis in Japan: first report of the pediatric rheumatology
association of Japan (PRAJ). Pediatr Rheumatol Online J. 2019;17:15.

Библиографические ссылки

Cassidy J. T. Textbook of pediatric rheumatology. 6th edn. Philadelphia: Saunders. 2011. 800 p.

Conrad K., Schlosler W., Hiepe F., Fitzler M.J. Autoantibodies in Organ Specific Autoimmune Diseases: A Diagnostic Reference/ PABST, Dresden – 2011.

Marieke H, Anink J, Prince FHM, Twilt M, Vastert SJ, ten Cate R, Hoppenreijs EPAH, Armbrust W, Gorter SL. Trends in prescription of biological agents and outcomes of juvenile idiopathic arthritis: results of the Dutch national Arthritis and Biologics in Children Register. Ann Rheum Dis. 2015;74:1379–1386. Doi:10.1136/annrheumdis-2013-204641.

Petty RE, Laxer RM, Lindsley CB, Wedderburh LR, Title VI, Ross E. Textbook of pediatric rheumatology. 7th edn. Philadelphia: WB Saunders. 2016. P. 205–216.

Kuna A.T. Mutated citrullinated vimentin antibodies in rheumatoid arthritis. Clin Chim Acta. 2012:413(1–2):66–73.

Turesson C., Mathsson L, Jacobsson L.T., Sturfelt G., Rönnelid J. Antibodies to modified citrullinated vimentin are associated with severe extra-articular manifestations in rheumatoid arthritis. Ann Rheum Dis. 2013:72(12):2047–2048.

Nicaise-Roland P., Nogueira L. et al. () Autoantibodies to citrullinated fibrinogen compared with anti-MCV and anti-CCP2 antibodies in diagnosing rheumatoid arthritis at an early stage: data from the French ESPOIR cohort. Ann Rheum Dis. 2013:72(3):357–362.

Avdeeva AS, Aleksandrova EN, Novikov AA, Smirnov AV, Cherkasova MV, Nasonov EL. The relationship of antibodies to modified citrullinated vimentin and markers of bone and cartilage destruction in rheumatoid arthritis. Int J Rheumatol 2014:2014:464585.

Derganova O, Martinez-Gamboa L, Egerer K, Bang H, Fredenhagen G, Roggenbuck D, et al. Selected cyclic citrullinated peptides derived from the sequence of mutated and citrullinated vimentin (MCV) are targeted by different antibodies subclasses in patients with rheumatoid arthritis in Russian patients. Clin Exp Rheumatol. 2014:32(5):622–629.

Díaz-Toscano M.L., Olivas-Flores E.M. et al. (2014) Comparison of two assays to determine anti-citrullinated peptide antibodies in rheumatoid arthritis in relation to other chronic inflammatory rheumatic diseases: assaying anti-modified citrullinated vimentin antibodies adds value to second-generation anti-citrullinated cyclic peptides testing. Biomed Res Int 2014:198198.

Reyes-Castillo Z., Palafox-Sánchez C.A. et al. Comparative analysis of autoantibodies targeting peptidylarginine deiminase type 4, mutated citrullinated vimentin and cyclic citrullinated peptides in rheumatoid arthritis: associations with cytokine profiles, clinical and genetic features. Clin Exp Immunol 2015;182(2):119-131.

Omar A, Abo-Elyoun I., Hussein H., Nabih M., Atwa H, Gad S. et al. Anti-cyclic citrullinated peptide (anti-CCP) antibody in juvenile idiopathic arthritis (JIA): correlations with disease activity and severity of joint damage (a multicenter trial). Joint Bone Spine. 2013:80(1):38–43. 13. Tebo A.E., Jaskowski T., Davis K.W., 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(1):29.

Gilliam B.E., Chauhan A.K., Moore T.L. Evaluation of anti-citrullinated type II collagen and anti-citrullinated vimentin antibodies in patients with juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2013;11(1):31.

Bulatović Calasan M., de Vries L.D., Vastert S.J., Heijstek M.W., Wulffraat N.M. Interpretation of the Juvenile Arthritis Disease Activity Score: responsiveness, clinically important differences and levels of disease activity in prospective cohorts of patients with juvenile idiopathic arthritis. Rheumatology (Oxford). 2014;53(2):307–312.

Bartoloni E, Alunno A, Bistoni O, Bizzaro N, Migliorini P, Morozzi G, Forum Interdisciplinare per la Ricerca nelle Malattie Autoimmuni (FIRMA) investigators, et al. Diagnostic value of anti-mutated citrullinated vimentin in comparison to anti-cyclic citrullinated peptide and anti-viral citrullinated peptide 2 antibodies in rheumatoid arthritis: an Italian multicentric study and review of the literature. Autoimmun Rev. 2012;11(11):815–820.

Lipinska, J., Lipinska, S., Kasielski, M. et al. Anti-MCV and anti-CCP antibodies—diagnostic and prognostic value in children with juvenile idiopathic arthritis (JIA). Clin.Rheumatol. 2016;35:2699–2706.

Mohamed Adly Khoudary Zeidan, Ahmed Mohammed Abd El-Rahman Tahoun, Tarek Abd El-Kareim El-Dahshan et al. Аnti-cyclic citrullinated peptide antibodies versus anti-mutated citrullinated vimentin antibodies in juvenile idiopathic arthritisl. Azhar Med. J. ( Medicine). Vol. 50 (1), January, 2021, 783 – 790.

Lucia Maria Sur, Remus Gaga, Genel Sur, and Emanuela Floca, “The Utility of CCP Antibodies in Autoimmune Diseases.” International Journal of Celiac Disease, 2020.- Vol. 8. -№2.- С.58-59.

Yasumura J, Yashiro M, Okamoto N, Shabana K, Umebayashi H, Iwata N, Okura Y, Kubota T, Shimizu M, Tomiita M, Nakagishi Y, Nishimura K, Hara R, Mizuta M, Yasumi T, Yamaide F, Wakiguchi H, Kobayashi M, Mori M. Clinical features and characteristics of uveitis associated with juvenile idiopathic arthritis in Japan: first report of the pediatric rheumatology association of Japan (PRAJ). Pediatr Rheumatol Online J. 2019;17:15.

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