Keywords
capillaroscopy
autoantibodies
immunological abnormalities
Categories
How to Cite
Abstract
Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease with multifaceted clinical manifestations, unclear etiology, and specific immunological phenomena that continue to be a challenge for modern science regarding their etiopathogenetic role in the onset and course of the disease. In SSc, different autoantibodies could be detected, and three are defined as diagnostic. They are considered potential biomarkers as they may eventually be used to distinguish distinct patient groups with specific clinical manifestations. Three specific autoantibodies and capillaroscopic abnormalities were included in the 2013 ACR/EULAR classification criteria for SSc. The autoantibodies defined as diagnostic in SSc are anti-centromere, anti-topoisomerase I, and anti-RNA polymerase III antibodies. Other SSc-associated antibodies are anti-Th/To, Ku, PDGFR, PM-Scl, etc. Growing evidence suggests an association between specific autoantibody profiles and distinct capillaroscopic patterns, indicating a link between immunological mechanisms and microvascular damage.
References
1. Denton CP, Khanna D. Systemic sclerosis. The Lancet 2017;390:1685–99. https://doi.org/10.1016/S0140-6736(17)30933-9.
2. Guiducci S, Bellando-Randone S, Matucci-Cerinic M. A New Way of Thinking about Systemic Sclerosis: The Opportunity for a Very Early Diagnosis. Isr Med Assoc J 2016;18:141–3.
3. van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 Classification Criteria for Systemic Sclerosis: An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Arthritis Rheum 2013;65:2737–47. https://doi.org/10.1002/art.38098.
4. Bellando-Randone S, Guiducci S, Matucci-Cerinic M. Very early diagnosis of systemic sclerosis. Pol Arch Med Wewn 2012;122 Suppl 1:18–23.
5. LeRoy EC, Medsger TA. Criteria for the classification of early systemic sclerosis. J Rheumatol 2001;28:1573–6.
6. Marković I, Posavec AL, Morović-Vergles J, Mitrović J. Very Early Diagnosis of Systemic Sclerosis in Clinical Practice - Case Report and Review of the Literature. Acta Dermatovenerol Croat 2022;30:251–5.
7. Bellando-Randone S, Matucci-Cerinic M. From Raynaud’s Phenomenon to Very Early Diagnosis of Systemic Sclerosis- The VEDOSS approach. Curr Rheumatol Rev 2014;9:245–8. https://doi.org/10.2174/157339710904140417124819.
8. Cutolo M, Sulli A, Pizzorni C, Accardo S. Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J Rheumatol 2000;27:155–60.
9. Cavazzana I, Vojinovic T, Airo’ P, Fredi M, Ceribelli A, Pedretti E, et al. Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers. Clin Rev Allergy Immunol 2022;64:412–30. https://doi.org/10.1007/s12016-022-08946-w.
10. Lambova SN. The Value of Nailfold Capillaroscopy in the Classification and Differential Diagnosis of Raynaud’s Phenomenon in Rheumatology. Curr Rheumatol Rev 2024;20:108–14. https://doi.org/10.2174/1573397119666230905151903.
11. Maricq HR, Carwile LeRoy E. Patterns of finger capillary abnormalities in connective tissue disease by “wide‐field” microscopy. Arthritis Rheum 1973;16:619–28. https://doi.org/10.1002/art.1780160506.
12. Bissell L-A, Abignano G, Emery P, Del Galdo F, Buch MH. Absence of Scleroderma pattern at nail fold capillaroscopy valuable in the exclusion of Scleroderma in unselected patients with Raynaud’s Phenomenon. BMC Musculoskelet Disord 2016;17:342. https://doi.org/10.1186/s12891-016-1206-5.
13. Mehra S, Walker J, Patterson K, Fritzler MJ. Autoantibodies in systemic sclerosis. Autoimmun Rev 2013;12:340–54. https://doi.org/10.1016/j.autrev.2012.05.011.
14. Douvas AS, Achten M, Tan EM. Identification of a nuclear protein (Scl-70) as a unique target of human antinuclear antibodies in scleroderma. J Biol Chem 1979;254:10514–22.
15. Gelber AC, Manno RL, Shah AA, Woods A, Le EN, Boin F, et al. Race and association with disease manifestations and mortality in scleroderma: a 20-year experience at the Johns Hopkins Scleroderma Center and review of the literature. Medicine 2013;92:191–205. https://doi.org/10.1097/MD.0b013e31829be125.
16. Cutolo M, Pizzorni C, Tuccio M, Burroni A, Craviotto C, Basso M, et al. Nailfold videocapillaroscopic patterns and serum autoantibodies in systemic sclerosis. Rheumatology (Oxford) 2004;43:719–26. https://doi.org/10.1093/rheumatology/keh156.
17. Sulli A, Ruaro B, Smith V, Pizzorni C, Zampogna G, Gallo M, et al. Progression of Nailfold Microvascular Damage and Antinuclear Antibody Pattern in Systemic Sclerosis. J Rheumatol 2013;40:634–9. https://doi.org/10.3899/jrheum.121089.
18. Ingegnoli F, Ardoino I, Boracchi P, Cutolo M, Airò P, Ananieva LP, et al. Nailfold capillaroscopy in systemic sclerosis: Data from the EULAR scleroderma trials and research (EUSTAR) database. Microvasc Res 2013;89:122–8. https://doi.org/10.1016/j.mvr.2013.06.003.
19. Valentini G, Marcoccia A, Cuomo G, Vettori S, Iudici M, Bondanini F, et al. Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers. Arthritis Res Ther 2013;15:R63. https://doi.org/10.1186/ar4236.
20. Earnshaw WC, Machlin PS, Bordwell BJ, Rothfield NF, Cleveland DW. Analysis of anticentromere autoantibodies using cloned autoantigen CENP-B. Proc Natl Acad Sci U S A 1987;84:4979–83. https://doi.org/10.1073/pnas.84.14.4979.
21. Koenig M, Dieudé M, Senécal J-L. Predictive value of antinuclear autoantibodies: The lessons of the systemic sclerosis autoantibodies. Autoimmun Rev 2008;7:588–93. https://doi.org/10.1016/j.autrev.2008.06.010.
22. Caetano J, Nihtyanova SI, Harvey J, Denton CP, Ong VH. Distinctive clinical phenotype of anti-centromere antibody-positive diffuse systemic sclerosis. Rheumatol Adv Pract 2018;2. https://doi.org/10.1093/rap/rky002.
23. Hysa E, Campitiello R, Sammorì S, Gotelli E, Cere A, Pesce G, et al. Specific Autoantibodies and Microvascular Damage Progression Assessed by Nailfold Videocapillaroscopy in Systemic Sclerosis: Are There Peculiar Associations? An Update. Antibodies 2023;12:3. https://doi.org/10.3390/antib12010003.
24. Lazzaroni M-G, Airò P. Anti-RNA polymerase III antibodies in patients with suspected and definite systemic sclerosis: Why and how to screen. J Scleroderma Relat Disord 2018;3:214–20. https://doi.org/10.1177/2397198318786158.
25. Wirz EG, Jaeger VK, Allanore Y, Riemekasten G, Hachulla E, Distler O, et al. Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis: a 10-year longitudinal study from the EUSTAR database. Ann Rheum Dis 2016;75:1285–92. https://doi.org/10.1136/annrheumdis-2015-207271.
26. Shanmugam VK, Steen VD. Renal disease in scleroderma. Curr Opin Rheumatol 2012;24:669–76. https://doi.org/10.1097/BOR.0b013e3283588dcf.
27. Koenig M, Joyal F, Fritzler MJ, Roussin A, Abrahamowicz M, Boire G, et al. Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud’s phenomenon to systemic sclerosis: A twenty‐year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis Rheum 2008;58:3902–12. https://doi.org/10.1002/art.24038.
28. Salazar GA, Assassi S, Wigley F, Hummers L, Varga J, Hinchcliff M, et al. Antinuclear antibody-negative systemic sclerosis. Semin Arthritis Rheum 2015;44:680–6. https://doi.org/10.1016/j.semarthrit.2014.11.006.
29. Lambova SN, Kurteva EK, Dzhambazova SS, Vasilev GH, Kyurkchiev DS, Geneva-Popova MG. Capillaroscopy and Immunological Profile in Systemic Sclerosis 2022;12:498. https://doi.org/10.3390/life12040498.
30. Tieu J, Hakendorf P, Woodman RJ, Patterson K, Walker J, Roberts‐Thomson P. The role of nailfold capillary dropout on mortality in systemic sclerosis. Intern Med J 2018;48:517–23. https://doi.org/10.1111/imj.13745.
31. HAMAGUCHI Y. Autoantibody profiles in systemic sclerosis: Predictive value for clinical evaluation and prognosis. J Dermatol 2010;37:42–53. https://doi.org/10.1111/j.1346-8138.2009.00762.x.
32. Aggarwal R, Lucas M, Fertig N, Oddis C V., Medsger TA. Anti–U3 RNP autoantibodies in systemic sclerosis. Arthritis Rheum 2009;60:1112–8. https://doi.org/10.1002/art.24409.
33. Możdżan M, Węgiel A, Biskup L, Brzezińska O, Makowska J. Anti-Th/To Antibodies in Scleroderma: Good Prognosis or Serious Concern? J Clin Med 2024;13:3022. https://doi.org/10.3390/jcm13113022.
34. Trefler J, Pasierb A, Lech L, Czaplicki H, Życińska K. Capillaroscopic patterns are associated with interstitial lung disease, skin fibrosis, anti-Th/To antibodies and quality of life in systemic sclerosis: a prospective cross-sectional study. Front Med (Lausanne) 2026;13. https://doi.org/10.3389/fmed.2026.1808581.
35. Rozman B, Čučnik S, Sodin-Semrl S, Czirják L, VarjÃo C, Distler O, et al. Prevalence and clinical associations of anti-Ku antibodies in patients with systemic sclerosis: a European EUSTAR-initiated multi-centre case–control study. Ann Rheum Dis 2008;67:1282–6. https://doi.org/10.1136/ard.2007.073981.
36. Nihtyanova SI, Denton CP. Autoantibodies as predictive tools in systemic sclerosis. Nat Rev Rheumatol 2010;6:112–6. https://doi.org/10.1038/nrrheum.2009.238.
37. Boulon C, Larrouture I, Blaise S, Mangin M, Chevoir JD Le, Senet P, et al. Nailfold video capillaroscopy predicts severe progression at three years in systemic sclerosis: Results from SCLEROCAP study. Microvasc Res 2026;163:104874. https://doi.org/10.1016/J.MVR.2025.104874.
38. Dimitrov S, Bogdanova S, Apostolova Z, Kasapska B, Kabakchieva P, Georgiev T. Transition to Artificial Intelligence in Imaging and Laboratory Diagnostics in Rheumatology. Applied Sciences 2025;15:11666. https://doi.org/10.3390/app152111666.
39. Doncheva-Dilova J, Stoilov N, Boyadzhieva V. Artificial intelligence (AI) and capillaroscopy: new horizons. Rheumatology (Bulgaria) 2026;33:11–23. https://doi.org/10.35465/rbj.rbj.406.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2026 Sanie Dzhambazova, Sevdalina Lambova (Author)