Significance of anti-carbamylated fibrinogen antibodies in systemic lupus erythematosus

  • Ying-ni LI ,
  • Xiao-hong XIANG ,
  • Jing ZHAO ,
  • Yun LI ,
  • Feng SUN ,
  • Hong-yan WANG ,
  • Ru-lin JIA ,
  • Fan-lei HU
Expand
  • Department of Rheumatology & Immunology, Peking University People’s Hospital, Beijing 100044, China

Received date: 2019-08-10

  Online published: 2019-12-19

Supported by

Supported by the National Natural Science Foundation of China (81671604, 81302554, 31530020)(81671604);Supported by the National Natural Science Foundation of China (81671604, 81302554, 31530020)(81302554);Supported by the National Natural Science Foundation of China (81671604, 81302554, 31530020)(31530020);the Beijing Nova Program(Z181100006218044);the Fundamental Research Funds for Central Universities: Peking University Clinical Medcine Plus X-Young Scholars Project(PKU2019LCXQ018)

Abstract

Objective: Antibodies against carbamylated protein (anti-CarP) were found to be a promising marker to evaluate joint damage and disease activity in patients with rheumatoid arthritis (RA). However, whether anti-CarP antibodies were present in systemic lupus erythematosus (SLE) remained ambiguity. We have therefore undertaken this study to assess the levels of serum anti-CarP antibodies and to evaluate their clinical value in SLE.Methods: Serum levels of antibodies against carbamylated-fibrinogen (anti-CarP) were measured by enzyme-linked immunosorbent assay (ELISA) in 105 SLE patients and 73 healthy controls. Other clinical and laboratory measurements of the SLE patients were collected from medical records. Data analyses between anti-CarP antibodies and other laboratory measurements were performed using SPSS software for Windows 24.0.Results: The levels of serum anti-CarP antibodies in the patients with SLE were significantly higher than those in the healthy controls (P<0.05). There were significant differences between the anti-CarP-positive group and anti-CarP-negative group in many clinical features. The disease duration, values of ESR, CRP, RF, anti-cardiolipin, anti-dsDNA, D-dipolymer, IgA and IgG were significantly higher in the anti-CarP-positive group compared with the negative group (P<0.05). Conversely, the values of complement 3, complement 4, peripheral blood RBC, and hemoglobin were significantly lower in anti-CarP-positive group than in the negative group(P<0.05). Moreover, the incidence of increase of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), D-dipolymer, decrease of peripheral blood RBC, hemoglobin, complement 3, complement 4, and positive rate of anti-dsDNA were significant different between the two groups(P<0.05). The positive rate of anti-CarP (21.9%) was higher than that of anti-Sm (15.24%), and close to anti-ribosomal P protein (22.86%) in our SLE patients. In addition, anti-CarP antibody was present in the SLE patients lacking the disease specific antibodies, including anti-Sm (anti-CarP positive rate 20.2%, 18/89), anti-dsDNA (anti-CarP positive rate 9.3%, 4/43), anti-nucleosome (anti-CarP positive rate 12.5%, 6/48), and anti-ribosomal P protein antibody (anti-CarP positive rate 20.9%, 17/81). Moreover, the high levels of anti-CarP antibodies were correlated with short disease duration, low C3, C4, RBC, and hemoglobin (P<0.05), high ESR, CRP, IgA, IgG, RF, anti-cardiolipin, anti-dsDNA, and D-dipolymer (P<0.05).Conclusion: The level of anti-CarP antibody was increased in the serum of patients with SLE. There were correlations between anti-CarP antibodies and clinical and laboratory indicators of SLE patients.

Cite this article

Ying-ni LI , Xiao-hong XIANG , Jing ZHAO , Yun LI , Feng SUN , Hong-yan WANG , Ru-lin JIA , Fan-lei HU . Significance of anti-carbamylated fibrinogen antibodies in systemic lupus erythematosus[J]. Journal of Peking University(Health Sciences), 2019 , 51(6) : 1019 -1024 . DOI: 10.19723/j.issn.1671-167X.2019.06.007

References

[1] Lee SJ, Silverman E, Bargman JM . The role of antimalarial agents in the treatment of SLE and lupus nephritis[J]. Nat Rev Nephrol, 2011,7(12):718-729.
[2] Yaniv G, Twig G, Shor DB , et al. A volcanic explosion of autoantibodies in systemic lupus erythematosus: a diversity of 180 different antibodies found in SLE patients[J]. Autoimmun Rev, 2015,14(1):75-79.
[3] Sherer Y, Gorstein A, Fritzler MJ , et al. Autoantibody explosion in systemic lupus erythematosus: more than 100 different anti-bodies found in SLE patients[J]. Semin Arthritis Rheum, 2004,34(2):501-537.
[4] Betancur JF, Gómez-Puerta JA . Antinuclear antibodies mitotic patterns and their clinical associations [J/OL]. Ann Rheum Dis ( 2019-04-29)[2019-08-01].
[5] Bizzaro N, Villalta D, Giavarina D , et al. Are anti-nucleosome antibodies a better diagnostic marker than anti-dsDNA antibodies for systemic lupus erythematosus? A systematic review and a study of metanalysis[J]. Autoimmun Rev, 2012,12(2):97-106.
[6] Schreier SM, Steinkellner H, Jirovetz L , et al. S-carbamoylation impairs the oxidant scavenging activity of cysteine: its possible impact on increased LDL modification in uraemia[J]. Biochimie, 2011,93(4):772-777.
[7] Gross ML, Piecha G, Bierhaus A , et al. Glycated and carbamylated albumin are more “nephrotoxic” than unmodified albumin in the amphibian kidney[J]. Am J Physiol Renal Physiol, 2011,301(3):476-485.
[8] Trepanier DJ, Thibert RJ . Carbamylation of erythrocyte membrane aminophospholipids: an in vitro and in vivo study[J]. Clin Biochem, 1996,29(4):333-345.
[9] Shi J, Knevel R, Suwannalai P , et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage[J]. Proc Natl Acad Sci USA, 2011,108(42):17372-17377.
[10] Bergum B, Koro C, Delaleu N , et al. Antibodies against carbamylated proteins are present in primary Sj?gren’s syndrome and are associated with disease severity[J]. Ann Rheum Dis, 2016,75(8):1494-1500.
[11] Scinocca M, Bell DA, Racapé M , et al. Antihomocitrullinated fibrinogen antibodies are specific to rheumatoid arthritis and frequently bind citrullinated proteins/peptides[J]. J Rheumatol, 2014,41(2):270-279.
[12] López-Hoyos M, álvarez-Rodríguez L, Mahler M , et al. Anti-carbamylated protein antibodies in patients with ageing associated inflammatory chronic disorders[J]. Rheumatology (Oxford), 2016,55(4):764-766.
[13] Ziegelasch M, van Delft MA, Wallin P , et al. Antibodies against carbamylated proteins and cyclic citrullinated peptides in systemic lupus erythematosus: results from two welldefined European cohorts[J]. Arthritis Res Ther, 2016,18(1):289.
[14] Nakabo S, Yoshifuji H, Hashimoto M , et al. Anti-carbamylated protein antibodies are detectable in various connective tissue dis-eases[J]. J Rheumatol, 2017,44(9):1384-1388.
[15] Hochberg MC . Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus[J]. Arthritis Rheum, 1997,40(9):1725.
[16] Turunen S, Koivula MK, Risteli L , et al. Anticitrulline antibodies can be caused by homocitrulline-containing proteins in rabbits[J]. Arthritis Rheum, 2010,62(11):3345-3352.
[17] Shi J, van de Stadt LA, Levarht EWT , et al. Anti-carbamylated protein (anti-CarP) antibodies precede the onset of rheumatoid arthritis[J]. Ann Rheum Dis, 2014,73(4):780-783.
[18] Ceccarelli F, Perricone C, Colasanti T , et al. Anti-carbamylated protein antibodies as a new biomarker of erosive joint damage in systemic lupus erythematosus[J]. Arthritis Res Ther, 2018,20(1):126
[19] Ceccarelli F, Perricone C, Cipriano E , et al. Joint involvement in systemic lupus erythematosus: from pathogenesis to clinical assessment[J]. Semin Arthritis Rheum, 2017,47(1):53-64.
[20] Mastrangelo A, Colasanti T, Barbati C , et al. The role of post-translational protein modifications in rheumatological diseases: Focus on rheumatoid arthritis [J/OL]. J Immunol Res, 2015, 2015: 712490(2015-05-18)[2019-08-01].
Outlines

/