Clinical, histopathological, and immunohistochemical characteristics of patients with sicca syndrome with a focus score ≥ 1 in the minor salivary gland biopsy
Abstract
Introduction. Sjögren’s syndrome is a systemic autoimmune disease. The usefulness of immunohistochemistry in minor salivary gland biopsies has been described to be helpful in indirectly characterizing the lymphocyte phenotype in difficult diagnosis cases.
Objective. To describe sociodemographic, clinical, serological, histopathological, and immunohistochemical variables in patients with sicca syndrome and a minor salivary gland biopsy focus score greater than or equal to one.
Materials and methods. We conducted an observational, retrospective study that included patients under study for potential sicca syndrome whose minor salivary gland biopsy was available and had obtained a focus score greater than or equal to one. Immunohistochemistry was performed on the minor salivary gland biopsy with chromogen red staining for CD8 T lymphocytes and brown staining for CD4 T lymphocytes. Expression ratio of CD20:CD3 and CD4:CD8 markers was determined with the MoticEasyScan Pro 6™ (MOTIC) device and the QuPath™ software. Qualitative variables were analyzed using the chi-square or Fisher’s exact test, and quantitative variables were analyzed according to their assumption of normality.
Results. Twenty-eight patients were analyzed: 16 patients had Sjögren’s syndrome, and 8 of them had polyautoimmunity. An association was found between atrophy in the minor salivary gland biopsy and development of polyautoimmunity (OR = 11.1; 95% CI: 1.12-112; p value = 0.033). The CD20:CD3 and CD4:CD8 ratios were normal, with no statistically significant differences between patients with and without Sjögren’s syndrome. In the subgroup of patients with Sjögren’s syndrome, CD4 T lymphocytes were predominant, with 15 cases out of 16 with CD4:CD8 ratios equal to or greater than 2:1.
Conclusions. Glandular atrophy was associated with the development of polyautoimmunity and a predominance of CD4 T lymphocytes in patients with Sjögren’s syndrome. This finding highlights the potential value of immunohistochemistry of minor salivary gland biopsies in this group.
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References
1. Cafaro G, Croia C, Argyropoulou OD, Leone MC, Orlandi M, Finamore F, et al. One year in review 2019: Sjögren’s syndrome. Clin Exp Rheumatol 2019;37(Suppl.118):S3-15.
2. Stergiou IE, Poulaki A, Voulgarelis M. Pathogenetic mechanisms implicated in Sjögren’s syndrome lymphomagenesis: A review of the literature. J Clin Med. 2020;9:1-20. https://doi.org/10.3390/jcm9123794
3. Qin B, Wang J, Yang Z, Yang M, Ma N, Huang F, et al. Epidemiology of primary Sjögren’s syndrome: A systematic review and meta-analysis. Ann Rheum Dis. 2015;74:1983-9. https://doi.org/10.1136/ANNRHEUMDIS-2014-205375
4. Rojas-Villarraga A, Parra-Medina R, Escobar A, Nieto JFP. Síndrome de Sjögren: revisando conceptos y abordando nuevos paradigmas. Rev Colomb Reumatol. 2020;27:1-3. https://doi.org/10.1016/J.RCREU.2020.09.002
5. Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, et al. 2016 ACR-EULAR classification criteria for primary Sjögren’s syndrome: A consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol. 2017;69:35. https://doi.org/10.1002/ART.39859
6. Fisher BA, Jonsson R, Daniels T, Bombardieri M, Brown RM, Morgan P, et al. Standardization of labial salivary gland histopathology in clinical trials in primary Sjögren’s syndrome. Ann Rheum Dis. 2017;76:1161-8. https://doi.org/10.1136/ANNRHEUMDIS-2016-210448
7. Brito-Zerón P, Baldini C, Bootsma H, Bowman SJ, Jonsson R, Mariette X, et al. Sjögren syndrome. Nat Rev Dis Primers. 2016;2. https://doi.org/10.1038/NRDP.2016.47
8. Theander E, Henriksson G, Ljungberg O, Mandl T, Manthorpe R, Jacobsson LT. Lymphoma and other malignancies in primary Sjögren’s syndrome: A cohort study on cancer incidence and lymphoma predictors. Ann Rheum Dis. 2006;65:796-803. https://doi.org/10.1136/ARD.2005.041186
9. Villamizar-Rivera N, Olaya N. Determinación de la clonalidad en tejidos humanos. Iatreia. 2015;28:269-82. https://doi.org/10.17533/udea.iatreia.v28n3a05
10. Villamizar-Rivera N, Olaya N. Experiencia en el uso de los protocolos BIOMED-2 para el estudio de reordenamientos de TCR e inmunoglobulinas en proliferaciones linfoides en el Instituto Nacional de Cancerología, Colombia. Biomédica. 2022;42:64. https://doi.org/10.7705/biomedica.5940
11. Zhang Y, Yu D, Huang K, Huang C, Liu H, Sun X, et al. Evaluation of the diagnostic value of immunoglobulin clonal gene rearrangements in patients with parotid gland MALT lymphoma using BIOMED-2 protocol. Oral Surg Oral Med Oral Pathol Oral Radiol 2018;126:165-73. https://doi.org/10.1016/J.OOOO.2018.03.005
12. Magaki S, Hojat SA, Wei B, So A, Yong WH. An introduction to the performance of immunohistochemistry. Methods Mol Biol. 2019;1897:289-98. https://doi.org/10.1007/978-1-4939-8935-5_25
13. Valdez RM, Melo TS, Santos-Silva AR, Duarte A, Gueiros LA. Adverse post-operative events of salivary gland biopsies: A systematic review and meta-analysis. J Oral Pathol Med. 2022;51:152-9. https://doi.org/10.1111/JOP.13229
14. Sarmiento-Monroy JC, Gómez-Puerta JA. Poliautoinmunidad en síndrome de Sjögren. Rev Colomb Reumatol. 2020;27:58-66. https://doi.org/10.1016/j.rcreu.2020.07.003
15. Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal L, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019;95. https://doi.org/10.1016/J.JBI.2019.103208
16. Moreno-Quispe LA, Velarde-Grados IVN, Guzmán-Avalos M, De Arriba L, María López-Pintor R. Prevalence of sicca syndrome in the Peruvian population. Clin Exp Rheumatol. 2019;37(Suppl. 118):S65-9.
17. Chatzis LG, Koulouri V, Baldini C, Pezoulas VC, Voulgari P V., Skopouli FN, et al. Clinical and laboratory findings of primary Sjögren’s syndrome patients without sicca symptoms. Clin Exp Rheumatol. 2022;40:2298-302. https://doi.org/10.55563/clinexprheumatol/gqvyus
18. Lockshin MD, Levine AB, Erkan D. Patients with overlap autoimmune disease differ from those with “pure” disease. Lupus Sci Med. 2015;2. https://doi.org/10.1136/LUPUS-2015-000084
19. Alani H, Henty JR, Thompson NL, Jury E, Ciurtin C. Systematic review and meta-analysis of the epidemiology of poly-autoimmunity in Sjögren’s syndrome (secondary Sjögren’s syndrome) focusing on autoimmune rheumatic diseases. Scand J Rheumatol. 2018;47:141-54. https://doi.org/10.1080/03009742.2017.1324909
20. Szabo K, Papp G, Dezso B, Zeher M. The histopathology of labial salivary glands in primary Sjögren’s syndrome: Focusing on follicular helper T cells in the inflammatory infiltrates. Mediators Inflamm. 2014;2014. https://doi.org/10.1155/2014/631787
21. Dal Pozzolo R, Cafaro G, Perricone C, Calvacchi S, Bruno L, Colangelo A, et al. Salivary gland biopsy as a prognostic tool in Sjögren’s syndrome. Expert Rev Clin Immunol. 2024. https://doi.org/10.1080/1744666X.2024.2368189
22. Chatzis L, Goules A V., Pezoulas V, Baldini C, Gandolfo S, Skopouli FN, et al. A biomarker for lymphoma development in Sjogren’s syndrome: Salivary gland focus score. J Autoimmun. 2021;121. https://doi.org/10.1016/J.JAUT.2021.102648
23. Leehan KM, Pezant NP, Rasmussen A, Grundahl K, Moore JS, Radfar L, et al. Minor salivary gland fibrosis in Sjögren’s syndrome is elevated, associated with focus score and not solely a consequence of aging. Clin Exp Rheumatol. 2018;36:80.
24. Klein A, Klein J, Chacham M, Kleinman S, Shuster A, Peleg O, et al. Acinar atrophy, fibrosis and fatty changes are significantly more common than Sjogren’s syndrome in minor salivary gland biopsies. Medicina (B Aires). 2022;58. https://doi.org/10.3390/medicina58020175
25. Ozcakir-Tomruk C, Tanyeri H, Tabak L, Dogan O. The value of labial biopsy in the differential diagnosis of sarcoidosis and Sjögren’s sydrome and immunohistochemical analysis. Biotechnol Biotechnol Equip. 2011;25:2399-404. https://doi.org/10.5504/BBEQ.2011.0037
26. Sun W, Zhang N, Zhang Y, Shao Z, Gong L, Wei W. Immunophenotypes and clinical features of lymphocytes in the labial gland of primary Sjogren’s syndrome patients. J Clin Lab Anal. 2018;32. https://doi.org/10.1002/JCLA.22585
27. Alunno A, Carubbi F, Bistoni O, Caterbi S, Bartoloni E, Bigerna B, et al. CD4(-) CD8(-) T-cells in primary Sjögren’s syndrome: Association with the extent of glandular involvement. J Autoimmun. 2014;51:38-43. https://doi.org/10.1016/J.JAUT.2014.01.030
28. Selifanova E, Beketova T, Spagnuolo G, Leuci S, Turkina A. A novel proposal of salivary lymphocyte detection and phenotyping in patients affected by Sjogren’s syndrome. J Clin Med 2020;9. https://doi.org/10.3390/JCM9020521
29. Ono J, Toya S, Ogura I, Okada Y. Study of clinical factors, focus score, lymphocyte type and NF-κB pathway in Sjögren’s syndrome. Odontology. 2023;111:207-16. https://doi.org/10.1007/S10266-022-00728-2
30. van Ginkel MS, van der Sluis T, Bulthuis MLC, Buikema HJ, Haacke EA, Arends S, et al. Digital image analysis of intraepithelial B-lymphocytes to assess lymphoepithelial lesions in salivary glands of Sjögren’s syndrome patients. Rheumatology (Oxford). 2022;62:428-38. https://doi.org/10.1093/rheumatology/keac212
31. Trivedi A, Cornejo KM, O’Donnell P, Dresser K, Deng A. Employing immunohistochemical staining to labial minor salivary gland biopsies from patients with Sjogren’s syndrome increases diagnostic certainty. J Oral Pathol Med. 2021;50:98-102. https://doi.org/10.1111/JOP.13119
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