Journal of Peking University (Health Sciences) ›› 2020, Vol. 52 ›› Issue (6): 1009-1013. doi: 10.19723/j.issn.1671-167X.2020.06.004

Previous Articles     Next Articles

Significance of anti-tubulin-α-1C autoantibody in systemic sclerosis

Jing ZHAO,Feng SUN,Yun LI,Xiao-zhen ZHAO,Dan XU,Ying-ni LI,Yu-hui LI(),Xiao-lin SUN   

  1. Department of Rheumatology & Immunology, Peking University People’s Hospital, Beijing 100044, China
  • Received:2020-07-28 Online:2020-12-18 Published:2020-12-13
  • Contact: Yu-hui LI E-mail:liyuhui84@163.com
  • Supported by:
    National Natural Science Foundation of China(81801617)

RICH HTML

  

Abstract:

Objective: To detect the serum level of a novel autoantibody, anti-tubulin-α-1C, in patients with systemic sclerosis (SSc) and to investigate its clinical significance. Methods: Anti-tubulin-α-1C antibody levels were determined by enzyme-linked immunosorbent assay (ELISA) in 62 patients with SSc, 38 systemic lupus erythematosus (SLE), 24 primary Sj?gren’s syndrome (pSS) patients, and 30 healthy controls (HCs). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), immunoglobulin A(IgA), immunoglobulin M (IgM), immunoglobulin G (IgG), C3, C4, rheumatoid factor (RF), antinuclear antibody(ANA), anti-centromere antibodies( ACA), anticardiolipin (aCL), anti-dsDNA antibody, anti-Sm antibody, anti-RNP antibody, anti-Scl-70 antibody, anti-Ro52 antibody, anti-SSA antibody, anti-SSB antibody, centromere protein A(CENP-A), centromere protein B (CENP-B) were measured by standard laboratory techniques. Raynaud’s phenomenon and modified Rodnan skin score(MRSS) were recorded to evaluate the disease status of SSc. Independent sample t test, Chi square test, Mann-Whitney U test, Spearman rank correlation were used for statistical analyses. Results: The serum anti-tubulin-α-1C antibody concentration in SSc group was 81.24±34.38, the serum anti-tubulin-α-1C antibody concentration in SLE group was 87.84±38.52, the serum anti-tubulin-α-1C antibody concentration in pSS group was 59.79±25.24, and the serum anti-tubulin-α-1C antibody concentration in healthy group was 39.37±18.7. Multivariate analysis revealed that anti-tubulin-α-1C antibody levels were significantly increased in the SSc and SLE patients. The expression level of anti-tubulin-α-1C antibody in SSc was higher compared with the pSS group and the health control group (P<0.01). Further analysis demonstrated that the elevated anti-tubulin-α-1C antibody were correlated with the SSc inflammation and disease activity markers ESR(r=0.313, P=0.019), The levels of anti-tubulin-α-1C antibody were also significantly correlated with MRSS(r=0.636, P<0.01). The best cut-off value for the diagnose of SSc was 76.77 as mean+2SD value. The proportion of Raynaud's phenomenon was higher in the group of anti-tubulin-α-1C autoantibody-postive SSc patients than that in anti-tubulin-α-1C autoantibody negative group(71.4% vs. 37.5%, P=0.039). The proportions of anti-Scl-70 antibody, anti-CENP antibody and anti-cardiolipin antibody were higher in the group of anti-tubulin-α-1C autoantibody-postive SSc patients than in the anti-tubulin-α-1C autoantibody negative group (37.9% vs. 15.2%, 34.5% vs. 12.1%, 13.8 vs. 0, respectively, all P<0.05). Conclusion: Based on this explorative stu-dy, the level of anti-tubulin-α-1C antibody increased in the serum of the patients with SSc. There were correlations between anti-tubulin-α-1C autoantibody and clinical and laboratory indicators of the SSc patients. It may become a novel biomarker indicative of active SSc and could be applied in future clinical practice.

Key words: Systemic sclerosis, Anti-tubulin-α-1C antibody, Autoantibodies

CLC Number: 

  • R783.2

Table 1

Clinical and laboratory characteristics of SSc patients with the elevated and normal levels of serum anti-tubulin-α-1C"

Items Anti-tubulin-α-1C(+)(n=29) Anti-tubulin-α-1C(-)(n=33) P
Female, n(%) 26 (89.7) 31 (93.9) 0.537
Age/years, x-±s 59.07±20.42 51.88±10.45 0.081
ESR /(mm/h), M(Min, Max) 21 (7-110) 12 (2-55) 0.033*
CRP/(mg/L), M(Min, Max) 2.49 (0.54-73.90) 2.95 (0.38-44.21) 0.431
C3/(g/L), x-±s 0.87±0.23 0.87±0.26 0.966
C4/(g/L), x-±s 0.22±0.09 0.24±0.26 0.667
RF/(IU/mL), M(Min, Max) 20 (20-123) 20 (18-3 710) 0.781
Anti-Ro52 positive, n(%) 8 (27.6) 16 (48.5) 0.090
Anti-RNP positive, n(%) 7 (24.1) 9 (27.3) 0.780
Anti-Scl-70 positive, n(%) 11 (37.9) 5 (15.2) 0.041*
ANA positive, n(%) 23 (79.3) 20 (60.6) 0.110
ACA positive, n(%) 10 (34.5) 4 (12.1) 0.035*
CENP A or B positive, n(%) 6 (20.7) 6 (18.2) 0.803
aCL positive, n(%) 4 (13.8) 0 0.043*
Anti-dsDNA positive, n(%) 4 (13.79) 1 (3.03) 0.120
IgA/(g/L), x-±s 3.37±2.89 2.52±1.80 0.164
IgG/(g/L), x-±s 15.30±6.61 14.60±6.82 0.681
IgM/(g/L), x-±s 1.17±0.81 0.99±0.70 0.350
Raynaud’s phenomenon, n(%) 15 (71.4) 6 (37.5) 0.039*

Table 2

Correlation of serum anti-tubulin-α-1C with clinical features of SSc patients"

Items r P
Age/years 0.023 0.860
Disease duration 0.118 0.455
ESR 0.313 0.019*
CRP -0.109 0.432
IgA 0.121 0.350
IgG 0.168 0.193
IgM 0.114 0.384
C3 -0.042 0.744
C4 0.086 0.513
RF -0.079 0.541
aCL 0.330 0.106
Anti-dsDNA 0.146 0.477
MRSS 0.636 <0.001*
[1] Denton CP, Khanna D. Systemic sclerosis[J]. Lancet, 2017,390(10103):1685-1699.
doi: 10.1016/S0140-6736(17)30933-9 pmid: 28413064
[2] Allanore Y, Simms R, Distler O, et al. Systemic sclerosis[J]. Nat Rev Dis Primers, 2015,1:15002
doi: 10.1038/nrdp.2015.2 pmid: 27189141
[3] Orlandi M, Barsotti S, Lepri G, et al. One year in review 2018: systemic sclerosis[J]. Clin Exp Rheumatol, 2018,113(4):3-23.
[4] Pattanaik D, Brown M, Postlethwaite BC, et al. Pathogenesis of systemic sclerosiss[J]. Front Immunol, 2015,6:272.
doi: 10.3389/fimmu.2015.00272 pmid: 26106387
[5] Chaaban S, Brouhard GJ. A microtubule bestiary: Structural diversity in tubulin polymerss[J]. Mol Biol Cell, 2017,28(22):2924-2931.
doi: 10.1091/mbc.E16-05-0271 pmid: 29084910
[6] Roll-Mecak A. How cells exploit tubulin diversity to build functional cellular microtubule mosaicss[J]. Curr Opin Cell Biol, 2019,56:102-108.
doi: 10.1016/j.ceb.2018.10.009 pmid: 30466050
[7] Kowal-Bielecka O, Fransen J, Avouac J, et al. Update of EULAR recommendations for the treatment of systemic sclerosis[J]. Ann Rheum Dis, 2017,76(8):1327-1339.
doi: 10.1136/annrheumdis-2016-209909 pmid: 27941129
[8] Avrameas S, Guilbert B, Dighiero G. Natural antibodies against tubulin, actin myoglobin, thyroglobulin, fetuin, albumin and transferrin are present in normal human sera, and monoclonal immunoglobulins from multiple myeloma and Waldenström’s macroglobulinemia may express similar antibody specificities[J]. Ann Immunol (Paris), 1981,132(2):231-236.
[9] Guilbert B, Dighiero G, Avrameas S. Naturally occurring anti-bodies against nine common antigens in human sera. Ⅰ. Detection, isolation and characterization[J]. J Immunol, 1982,128(6):2779-2787.
pmid: 6176652
[10] Karsenti E, Guilbert B, Bornens M, et al. Anti-actin and anti-tubulin antibodies in the serum of non-immunized animals[J]. Ann Immunol (Paris), 1977,128(1/2):195-200.
[11] Kurki P, Virtanen I. The detection of human antibodies against cytoskeletal components[J]. J Immunol Methods, 1984,67(2):209-223.
pmid: 6200533
[12] Ludueña RF. A hypojournal on the origin and evolution of tubulin[J]. Int Rev Cell Mol Biol, 2013,302:41-185.
doi: 10.1016/B978-0-12-407699-0.00002-9 pmid: 23351710
[13] Burbelo PD, Gordon SM, Waldman M, et al. Autoantibodies are present before the clinical diagnosis of systemic sclerosis[J]. PLoS One, 2019,14(3):e0214202.
pmid: 30913258
[14] Cheng Y, Zhao X, Chen Y, et al. Circulating immune comple-xome analysis identified anti-tubulin-α-1C as an inflammation associated autoantibody with promising diagnostic value for Behcet’s disease[J]. PLoS One, 2018,13(6):e0199047.
doi: 10.1371/journal.pone.0199047 pmid: 29902281
[15] Zhao X, Cheng Y, Gan Y, et al. Anti-tubulin-α-1C autoantibody in systemic lupus erythematosus: a novel indicator of disease acti-vity and vasculitis manifestationse[J]. Clin Rheumatol, 2018,37(5):1229-1237.
doi: 10.1007/s10067-018-4024-3 pmid: 29427009
[16] Goers TA, Ramachandran S, Aloush A, et al. De novo production of K-alpha1 tubulin-specific antibodies: role in chronic lung allograft rejection[J]. J Immunol, 2008,180(7):4487-4494.
pmid: 18354170
[17] Hachem RR, Tiriveedhi V, Patterson GA, et al. Antibodies to K-α1 tubulin and collagen V are associated with chronic rejection after lung transplantation[J]. Am J Transplant, 2012,12(8):2164-2171.
pmid: 22568593
[1] Zhengfang LI,Cainan LUO,Lijun WU,Xue WU,Xinyan MENG,Xiaomei CHEN,Yamei SHI,Yan ZHONG. Application value of anti-carbamylated protein antibody in the diagnosis of rheumatoid arthritis [J]. Journal of Peking University (Health Sciences), 2024, 56(4): 729-734.
[2] Zhanhong LAI,Jiachen LI,Zelin YUN,Yonggang ZHANG,Hao ZHANG,Xiaoyan XING,Miao SHAO,Yuebo JIN,Naidi WANG,Yimin LI,Yuhui LI,Zhanguo LI. A unicenter real-world study of the correlation factors for complete clinical response in idiopathic inflammatory myopathies [J]. Journal of Peking University (Health Sciences), 2024, 56(2): 284-292.
[3] Yan-hong MENG,Yi-fan CHEN,Pei-ru ZHOU. Clinical and immunological features of primary Sjögren's syndrome patients with positive anti-centromere protein B antibody [J]. Journal of Peking University (Health Sciences), 2023, 55(6): 1088-1096.
[4] Wen-gen LI,Xiao-dong GU,Rui-qiang WENG,Su-dong LIU,Chao CHEN. Expression and clinical significance of plasma exosomal miR-34-5p and miR-142-3p in systemic sclerosis [J]. Journal of Peking University (Health Sciences), 2023, 55(6): 1022-1027.
[5] Zhuo-hua LIN,Ru-yi CAI,Yang SUN,Rong MU,Li-gang CUI. Methodology and clinical use of superb microvascular imaging in assessing micro-circulation changes of fingertips in systemic sclerosis [J]. Journal of Peking University (Health Sciences), 2023, 55(4): 636-640.
[6] Xiao-yan XING,Jun-xiao ZHANG,Feng-yun-zhi ZHU,Yi-fan WANG,Xin-yao ZHOU,Yu-hui LI. Clinical analysis of 5 cases of dermatomyositis complicated with macrophage activation syndrome [J]. Journal of Peking University (Health Sciences), 2022, 54(6): 1214-1218.
[7] Lu ZHANG,Cheng CHEN,Mei-ting WENG,Ai-ping ZHENG,Mei-ling SU,Qing-wen WANG,Yue-ming CAI. Characteristics of serum autoantibodies in patients with lupus nephritis and tubulointerstitial damage [J]. Journal of Peking University (Health Sciences), 2022, 54(6): 1094-1098.
[8] XIAO Yun-shu,ZHU Feng-yun-zhi,LUO Lan,XING Xiao-yan,LI Yu-hui,ZHANG Xue-wu,SHEN Dan-hua. Clinical and immunological characteristics of 88 cases of overlap myositis [J]. Journal of Peking University (Health Sciences), 2021, 53(6): 1088-1093.
[9] LUO Lan,XING Xiao-yan,XIAO Yun-shu,CHEN Ke-yan,ZHU Feng-yun-zhi,ZHANG Xue-wu,LI Yu-hui. Clinical and immunological characteristics of patients with anti-synthetase syndrome complicated with cardiac involvement [J]. Journal of Peking University (Health Sciences), 2021, 53(6): 1078-1082.
[10] MA Xiang-bo,ZHANG Xue-wu,JIA Ru-lin,GAO Ying,LIU Hong-jiang,LIU Yu-fang,LI Ying-ni. Application of lymphocytes test in peripheral blood of patients with systemic sclerosis during the treatment [J]. Journal of Peking University (Health Sciences), 2021, 53(4): 721-727.
[11] Feng-yun-zhi ZHU,Xiao-yan XING,Xiao-fei TANG,Yi-min LI,Miao SHAO,Xue-Wu ZHANG,Yu-hui LI,Xiao-lin SUN,Jing HE. Clinical and immunological characteristics of myositis complicated with thromboembolism [J]. Journal of Peking University (Health Sciences), 2020, 52(6): 995-1000.
[12] Yi-ming ZHENG,Hong-jun HAO,Yi-lin LIU,Jing GUO,Ya-wen ZHAO,Wei ZHANG,Yun YUAN. Correlation study on anti-Ro52 antibodies frequently co-occur with other myositis-specific and myositis-associated autoantibodies [J]. Journal of Peking University (Health Sciences), 2020, 52(6): 1088-1092.
[13] Hong-lin ZHU,Qian DU,Wei-lin CHEN,Xiao-xia ZUO,Quan-zhen LI,Si-jia LIU. Altered serum cytokine expression profile in systemic sclerosis and its regulatory mechanisms [J]. Journal of Peking University(Health Sciences), 2019, 51(4): 716-722.
[14] XU Jing, LIU Jing,ZHU Lei, ZHANG Xue-wu, LI Zhan-guo. Significance of glucose-6-phosphate isomerase assay in early diagnosis of rheumatoid arthritis [J]. Journal of Peking University(Health Sciences), 2016, 48(6): 942-946.
[15] WANG Lin-Lin, YANG Na, YUAN Yue, REN Ai-Guo. Establishment and evaluation of enzyme-linked immunosorbent assay for measuring human autoantibody IgG to folate receptor [J]. Journal of Peking University(Health Sciences), 2014, 46(3): 483-487.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!