nach oben

Erschienen in:

20.07.2021 | Observational Research

Focal lymphocytic sialadenitis and ectopic germinal centers in oral reactive lesions and primary Sjögren’s syndrome: a comparative study

verfasst von: Evânio Vilela Silva, Luciana Yamamoto Almeida, Karen Cristine Bortoletto, Isabela Barbosa Quero, Fernanda Carolina Jacomini, Bruno Augusto Benevenuto de Andrade, Heitor Albergoni Silveira, Andressa Duarte, Flávio Calil Petean, Eduardo Melani Rocha, Alfredo Ribeiro-Silva, Román Carlos, Jorge Esquiche León

Erschienen in: Rheumatology International | Ausgabe 8/2022

Einloggen, um Zugang zu erhalten

Abstract

Focal lymphocytic sialadenitis (FLS), an important diagnostic criterion for Sjögren’s syndrome (SS) diagnosis, can also be observed when assessing minor salivary gland (mSG) biopsies from healthy asymptomatic individuals (non-SS patients). Fifty cases of primary SS (pSS group) and 31 cases of oral reactive lesions (non-SS non-sicca group) containing also typical FLS features, were assessed by morphological and immunohistochemical (CD10, CD23 and Bcl-6) analysis, aiming at the detection of GCs. All pSS cases showed FLS with focus score (FS) ≥ 1. In the non-SS non-sicca group, 12, 10 and 9 cases showed FLS with FS ≥ 1, FLS with FS < 1 and FLS associated with chronic sclerosing sialadenitis with FS < 1, respectively. The morphological analysis revealed similar frequency of GCs in pSS (20%) and non-SS non-sicca group (19%). The area (p = 0.052) and largest diameter (p = 0.245) of GCs were higher in pSS than non-SS non-sicca group. The FS and number of foci were significantly higher in pSS than non-SS non-sicca group with FS < 1. Immunohistochemistry confirmed all morphological findings (GCs showing CD23 and Bcl-6 positivity, with variable CD10 expression) and additionally in 3 and 1 cases of the pSS and non-SS non-sicca group, respectively. Moreover, another 6 and 2 cases of the pSS and non-SS non-sicca group with FS ≥ 1, respectively, showed positivity only for CD23. FLS can also be observed when assessing oral reactive lesions, which showed similar frequency of GCs with those found in pSS patients. Further studies, including functional analysis of lymphocytic populations and GCs in FLS, are encouraged.

Nur mit Berechtigung zugänglich

Jonsson MV, Szodoray P, Jellestad S, Jonsson R, Skarstein K (2005) Association between circulating levels of the novel TNF family members APRIL and BAFF and lymphoid organization in primary Sjögren’s syndrome. J Clin Immunol 25(3):189–201. https://doi.org/10.1007/s10875-005-4091-5CrossRefPubMed

Mariette X, Criswell LA (2018) Primary Sjögren’s syndrome. N Engl J Med 378(10):931–939. https://doi.org/10.1056/NEJMcp1702514CrossRefPubMed

Johnsen SJ, Berget E, Jonsson MV, Helgeland L, Omdal R, Jonsson R (2014) Evaluation of germinal center-like structures and B cell clonality in patients with primary sjögren syndrome with and without Lymphoma. J Rheumatol 41(11):2214–2222. https://doi.org/10.3899/jrheum.131527CrossRefPubMed

Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM et al (2017) 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren’s syndrome: a consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol 69(1):35–45. https://doi.org/10.1002/art.39859CrossRefPubMed

Risselada AP, Looije MF, Kruize AA, Bijlsma JWJ, Van Roon JAG (2013) The role of ectopic germinal centers in the immunopathology of primary Sjögren’s syndrome: a systematic review. Semin Arthritis Rheum 42:368–376. https://doi.org/10.1016/j.semarthrit.2012.07.003CrossRefPubMed

Jonsson MV, Skarstein K, Jonsson R, Brun JG (2007) Serological implications of germinal center-like structures in primary Sjögren’s syndrome. J Rheumatol 34:2044–2049PubMed

Reksten TR, Jonsson MV, Szyszko EA, Brun JG, Jonsson R, Brokstad KA (2009) Cytokine and autoantibody profiling related to histopathological features in primary Sjögren’s syndrome. Rheumatology 48(9):1102–1106. https://doi.org/10.1093/rheumatology/kep149CrossRefPubMed

Lee KE, Kang JH, Yim YR, Kim JE, Lee JW, Wen L et al (2016) The significance of ectopic germinal centers in the minor salivary gland of patients with Sjögren’s syndrome. J Korean Med Sci 31(2):190–195. https://doi.org/10.3346/jkms.2016.31.2.190CrossRefPubMedPubMedCentral

He J, Jin Y, Zhang X, Zhou Y, Li R, Dai Y et al (2017) Characteristics of germinal center-like structures in patients with Sjögren’s syndrome. Int J Rheum Dis 20(2):245–521. https://doi.org/10.1111/1756-185X.12856CrossRefPubMed

10.

Theander E, Vasaitis L, Baecklund E, Nordmark G, Warfvinge G, Liedholm R et al (2011) Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sjögren’s syndrome. Ann Rheum Dis 70:1363–1368. https://doi.org/10.1136/ard.2010.144782CrossRefPubMed

11.

Sène D, Ismael S, Forien M, Charlotte F, Kaci R, Cacoub P et al (2018) Ectopic germinal center–like structures in minor salivary gland biopsy tissue predict lymphoma occurrence in patients with primary Sjögren’s syndrome. Arthritis Rheumatol 70(9):1481–1488. https://doi.org/10.1002/art.40528CrossRefPubMed

12.

Bombardieri M, Barone F, Humby F, Kelly S, McGurk M, Morgan P et al (2007) Activation-induced cytidine deaminase expression in follicular dendritic cell networks and interfollicular large B cells supports functionality of ectopic lymphoid neogenesis in autoimmune sialoadenitis and MALT lymphoma in Sjögren’s syndrome. J Immunol 179:4929–4938CrossRef

13.

Christodoulou MI, Kapsogeorgou EK, Moutsopoulos HM (2010) Characteristics of the minor salivary gland infiltrates in Sjögren’s syndrome. J Autoimmun 34(4):400–407. https://doi.org/10.1016/j.jaut.2009.10.004CrossRefPubMed

14.

Jonsson MV, Skarstein K (2008) Follicular dendritic cells confirm lymphoid organization in the minor salivary glands of primary Sjögren’s syndrome. J Oral Pathol Med 37(9):515–521. https://doi.org/10.1111/j.1600-0714.2008.00674.xCrossRefPubMed

15.

Szyszko EA, Brokstad KA, Øijordsbakken G, Jonsson MV, Jonsson R, Skarstein K (2011) Salivary glands of primary Sjögren’s syndrome patients express factors vital for plasma cell survival. Arthritis Res Ther 13(1):1–18. https://doi.org/10.1186/ar3220CrossRef

16.

Haacke EA, Van Der Vegt B, Vissink A, Spijkervet FKL, Bootsma H, Kroese FGM (2017) Germinal centres in diagnostic labial gland biopsies of patients with primary Sjogren’s syndrome are not predictive for parotid MALT lymphoma development. Ann Rheum Dis 76(10):1783–1786. https://doi.org/10.1136/annrheumdis-2017-211290CrossRef

17.

Haacke EA, van der Vegt B, Vissink A, Spijkervet FKL, Bootsma H, Kroese FGM (2019) Germinal centers in diagnostic biopsies of patients with primary Sjögren’s Syndrome are not a risk factor for non-Hodgkin’s lymphoma but a reflection of high disease activity: comment on the article by Sène et al. Arthritis Rheumatol 71(1):170–171. https://doi.org/10.1002/art.40715CrossRefPubMed

18.

Jonsson MV, Salomonsson S, Oijordsbakken G, Skarstein K (2005) Elevated serum levels of soluble E-cadherin in patients with primary Sjögren’s syndrome. Scand J Immunol 62(6):552–559. https://doi.org/10.1111/j.1365-3083.2005.01698.xCrossRefPubMed

19.

Pijpe J, Kalk WWI, van der Wal JE, Vissink A, Kluin PM, Roodenburg JLN et al (2007) Parotid gland biopsy compared with labial biopsy in the diagnosis of patients with primary Sjögren’s syndrome. Rheumatology 46(2):335–341. https://doi.org/10.1093/rheumatology/kel266CrossRefPubMed

20.

Delli K, Haacke EA, Kroese FGM, Pollard RP, Ihrler S, Van Der Vegt B et al (2016) Towards personalised treatment in primary Sjögren’s syndrome: baseline parotid histopathology predicts responsiveness to rituximab treatment. Ann Rheum Dis 75(11):1933–1938. https://doi.org/10.1136/annrheumdis-2015-208304CrossRefPubMed

21.

Nakshbandi U, Haacke EA, Bootsma H, Vissink A, Spijkervet FKL, van der Vegt B et al (2020) Bcl-6 for identification of germinal centres in salivary gland biopsies in primary Sjögren’s syndrome. Oral Dis 26(3):707–710. https://doi.org/10.1111/odi.13276CrossRefPubMedPubMedCentral

22.

Daridon C, Pers JO, Devauchelle V, Martins-Carvalho C, Hutin P, Pennec YL et al (2006) Identification of transitional type II B cells in the salivary glands of patients with Sjögren’s syndrome. Arthritis Rheum 54(7):2280–2288. https://doi.org/10.1002/art.21936CrossRefPubMed

23.

Le Pottier L, Devauchelle V, Fautrel A, Daridon C, Saraux A, Youinou P et al (2009) Ectopic germinal centers are rare in Sjogren’s syndrome salivary glands and do not exclude autoreactive B cells. J Immunol 182(6):3540–3547. https://doi.org/10.4049/jimmunol.0803588CrossRefPubMed

24.

Fei Y, Zhang W, Lin D, Wu C, Li M, Zhao Y et al (2014) Clinical parameter and Th17 related to lymphocytes infiltrating degree of labial salivary gland in primary Sjögren’s syndrome. Clin Rheumatol 33(4):523–529. https://doi.org/10.1007/s10067-013-2476-zCrossRefPubMed

25.

Scott J (1980) Qualitative and quantitative observations on the histology of human labial salivary glands obtained post mortem. J Biol Buccale 8:187–200PubMed

26.

Syrjänen S (1984) Age-related changes in structure of labial minor salivary glands. Age Ageing 13(3):159–165. https://doi.org/10.1093/ageing/13.3.159CrossRefPubMed

27.

De Wilde PC, Baak JP, van Houwelingen JC, Kater L, Slootweg PJ (1986) Morphometric study of histological changes in sublabial salivary glands due to aging process. J Clin Pathol 39(4):406–417. https://doi.org/10.1136/jcp.39.4.406CrossRefPubMedPubMedCentral

28.

Kurashima C, Hirokawa K (1986) Age-related increase of focal lymphocytic infiltration in the human submandibular glands. J Oral Pathol 15(3):172–178. https://doi.org/10.1111/j.1600-0714.1986.tb00601.xCrossRefPubMed

29.

Segerberg-Konttinen M, Konttinen YT, Bergroth V (1986) Focus score in the diagnosis of Sjögren’s syndrome. Scand J Rheumatol 61:47–51

30.

Takeda Y, Komori A (1986) Focal lymphocytic infiltration in the human labial salivary glands: a postmortem study. J Oral Pathol 15(2):83–86. https://doi.org/10.1111/j.1600-0714.1986.tb00582.xCrossRefPubMed

31.

Segerberg-Konttinen M (1989) A postmortem study of focal adenitis in salivary and lacrimal glands. J Autoimmun 2(4):553–558. https://doi.org/10.1016/0896-8411(89)90188-1CrossRefPubMed

32.

Vered M, Buchner A, Haimovici E, Hiss Y, Dayan D (2001) Focal lymphocytic infiltration in aging human palatal salivary glands: a comparative study with labial salivary glands. J oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol 30(1):7–11. https://doi.org/10.1034/j.1600-0714.2001.300102.xCrossRef

33.

Radfar L, Kleiner DE, Fox PC, Pillemer SR (2002) Prevalence and clinical significance of lymphocytic foci in minor salivary glands of healthy volunteers. Arthritis Rheum 47(5):520–524. https://doi.org/10.1002/art.10668CrossRefPubMed

34.

McIntosh GG, Lodge AJ, Watson P, Hall G, Wood K, Anderson JJ, Angus B, Horne CH, Milton ID (1999) NCL-CD10-270: a new monoclonal antibody recognizing CD10 in paraffin-embedded tissue. Am J Pathol 154(1):77–82. https://doi.org/10.1016/S0002-9440(10)65253-4CrossRefPubMedPubMedCentral

35.

Rangel ALCA, León JE, Jorge J, Lopes MA, Vargas PA (2008) Oncocytic metaplasia in inflammatory fibrous hyperplasia: Histopathological and immunohistochemical analysis. Med Oral Patol Oral Cir Bucal 13:151–155

36.

Fisher BA, Jonsson R, Daniels T, Bombardieri M, Brown RM, Morgan P et al (2017) Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren’s syndrome. Ann Rheum Dis 76(7):1161–1168. https://doi.org/10.1136/annrheumdis-2016-210448CrossRefPubMed

37.

Allen CDC, Cyster JG (2008) Follicular dendritic cell networks of primary follicles and germinal centers: phenotype and function. Semin Immunol 20(1):14–25. https://doi.org/10.1016/j.smim.2007.12.001CrossRefPubMedPubMedCentral

38.

Kurshumliu F, Sadiku-Zehri F, Qerimi A, Vela Z, Jashari F, Bytyci S et al (2019) Divergent immunohistochemical expression of CD21 and CD23 by follicular dendritic cells with increasing grade of follicular lymphoma. World J Surg Oncol 17(1):115. https://doi.org/10.1186/s12957-019-1659-8CrossRefPubMedPubMedCentral

39.

Maguer-Satta V, Besançon R, Bachelard-Cascales E (2011) Concise review: neutral endopeptidase (CD10): a multifaceted environment actor in stem cells, physiological mechanisms, and cancer. Stem Cells 29(3):389–396. https://doi.org/10.1002/stem.592CrossRefPubMed

40.

Beaulieu AM, Sant’Angelo DB (2011) The BTB-ZF family of transcription factors: key regulators of lineage commitment and effector function development in the immune system. J Immunol 187(6):2841–2847. https://doi.org/10.4049/jimmunol.1004006CrossRefPubMed

41.

Kim JR, Lim HW, Kang SG, Hillsamer P, Kim CH (2005) Human CD57+ germinal center-T cells are the major helpers for GC-B cells and induce class switch recombination. BMC Immunol 6:3. https://doi.org/10.1186/1471-2172-6-3CrossRefPubMedPubMedCentral

42.

Carubbi F, Alunno A, Cipriani P, Bartoloni E, Baldini C, Quartuccio L et al (2015) A retrospective, multicenter study evaluating the prognostic value of minor salivary gland histology in a large cohort of patients with primary Sjögren’s syndrome. Lupus 24(3):315–320. https://doi.org/10.1177/0961203314554251CrossRefPubMed

43.

Risselada AP, Kruize AA, Goldschmeding R, Lafeber FPJG, Bijlsma JWJ, van Roon JAG (2014) The prognostic value of routinely performed minor salivary gland assessments in primary Sjögren’s syndrome. Ann Rheum Dis 73(8):1537–1540. https://doi.org/10.1136/annrheumdis-2013-204634CrossRefPubMed

44.

Haacke EA, Bootsma H, Spijkervet FKL, Visser A, Vissink A, Kluin PM et al (2017) FcRL4(+) B-cells in salivary glands of primary Sjögren’s syndrome patients. J Autoimmun 81:90–98. https://doi.org/10.1016/j.jaut.2017.03.012CrossRefPubMed

45.

Ciccia F, Guggino G, Rizzo A, Bombardieri M, Raimondo S, Carubbi F et al (2015) Interleukin (IL)-22 receptor 1 is over-expressed in primary Sjogren’s syndrome and Sjögren-associated non-Hodgkin lymphomas and is regulated by IL-18. Clin Exp Immunol 181(2):219–229. https://doi.org/10.1111/cei.12643CrossRefPubMedPubMedCentral

46.

Johnsen SJA, Gudlaugsson E, Skaland I, Janssen EAM, Jonsson MV, Helgeland L et al (2016) Low protein A20 in minor salivary glands is associated with lymphoma in primary Sjögren’s syndrome. Scand J Immunol 83(3):181–187. https://doi.org/10.1111/sji.12405CrossRefPubMed

47.

Ussmüller J, Reinecke T, Donath K, Jaehne M (2002) Chronic myoepithelial sialadenitis - symptomatology, clinical signs, differential diagnostics. Laryngorhinootologie 81(2):111–117. https://doi.org/10.1055/s-2002-23111CrossRefPubMed

48.

Jonsson MV, Theander E, Jonsson R (2012) Predictors for the development of non-Hodgkin lymphoma in primary Sjögren’s syndrome. Presse Med 41(9 pt 2):e511-516. https://doi.org/10.1016/j.lpm.2012.05.025CrossRefPubMed

49.

Ioannidis JP, Vassiliou VA, Moutsopoulos HM (2002) Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjögren’s syndrome. Arthritis Rheum 46(3):741–747. https://doi.org/10.1002/art.10221CrossRefPubMed

50.

Theander E, Henriksson G, Ljungberg O, Mandl T, Manthorpe R, Jacobsson LT (2006) Lymphoma and other malignancies in primary Sjögren’s syndrome: a cohort study on cancer incidence and lymphoma predictors. Ann Rheum Dis 65(6):796–803. https://doi.org/10.1136/ard.2005.041186CrossRefPubMed

51.

Skopouli FN, Dafni U, Ioannidis JP, Moutsopoulos HM (2000) Clinical evolution, and morbidity and mortality of primary Sjögren’s syndrome. Semin Arthritis Rheum 29(5):296–304. https://doi.org/10.1016/s0049-0172(00)80016-5CrossRefPubMed

52.

Voulgarelis M, Dafni UG, Isenberg DA, Moutsopoulos HM (1999) Malignant lymphoma in primary Sjögren’s syndrome: a multicenter, retrospective, clinical study by the European Concerted Action on Sjögren’s Syndrome. Arthritis Rheum 42(8):1765–1772. https://doi.org/10.1002/1529-0131(199908)42:8%3c1765::AIDANR28%3e3.0.CO;2-CrossRefPubMed

53.

Voulgarelis M, Ziakas PD, Papageorgiou A, Baimpa E, Tzioufas AG, Moutsopoulos HM (2012) Prognosis and outcome of non-Hodgkin lymphoma in primary Sjögren syndrome. Medicine 91(1):1–9. https://doi.org/10.1097/MD.0b013e31824125e4CrossRefPubMed

54.

Tzioufas AG, Manoussakis MN, Costello R, Silis M, Papadopoulos NM, Moutsopoulos HM (1986) Cryoglobulinemia in autoimmune rheumatic diseases. Evidence of circulating monoclonal cryoglobulins in patients with primary Sjögren’s syndrome. Arthritis Rheum 29(9):1098–1104. https://doi.org/10.1002/art.1780290907CrossRefPubMed

55.

Hernández JA, Olivé A, Ribera JM, Tena X, Cuxart A, Feliu E (1996) Probability of the development of non-Hodgkin’s lymphoma in primary Sjögren’s syndrome. Scand J Rheum 25(6):396–397. https://doi.org/10.3109/03009749609065654CrossRefPubMed

56.

Szodoray P, Alex P, Jonsson MV, Knowlton N, Dozmorov I, Nakken B et al (2005) Distinct profiles of Sjögren’s syndrome patients with ectopic salivary gland germinal centers revealed by serum cytokines and BAFF. Clin Immunol 117(2):168–176. https://doi.org/10.1016/j.clim.2005.06.016CrossRefPubMed

57.

Gatumu MK, Jonsson MV, Øijordsbakken G, Skarstein K (2009) Nuclear BCL10 in primary Sjögren’s syndrome. J Oral Pathol Med 38(6):501–507. https://doi.org/10.1111/j.1600-0714.2009.00757.xCrossRefPubMed

58.

Manoussakis MN, Boiu S, Korkolopoulou P, Kapsogeorgou EK, Kavantzas N, Ziakas P et al (2007) Rates of infiltration by macrophages and dendritic cells and expression of interleukin-18 and interleukin-12 in the chronic inflammatory lesions of Sjögren’s syndrome: correlation with certain features of immune hyperactivity and factors associated with h. Arthritis Rheum 56(12):3977–3988. https://doi.org/10.1002/art.23073CrossRefPubMed

Titel: Focal lymphocytic sialadenitis and ectopic germinal centers in oral reactive lesions and primary Sjögren’s syndrome: a comparative study
verfasst von: Evânio Vilela Silva
Luciana Yamamoto Almeida
Karen Cristine Bortoletto
Isabela Barbosa Quero
Fernanda Carolina Jacomini
Bruno Augusto Benevenuto de Andrade
Heitor Albergoni Silveira
Andressa Duarte
Flávio Calil Petean
Eduardo Melani Rocha
Alfredo Ribeiro-Silva
Román Carlos
Jorge Esquiche León
Publikationsdatum: 20.07.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Rheumatology International / Ausgabe 8/2022
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-021-04949-6

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Schadet Ärger den Gefäßen?

14.05.2024 Arteriosklerose Nachrichten

In einer Studie aus New York wirkte sich Ärger kurzfristig deutlich negativ auf die Endothelfunktion gesunder Probanden aus. Möglicherweise hat dies Einfluss auf die kardiovaskuläre Gesundheit.

Intervallfasten zur Regeneration des Herzmuskels?

14.05.2024 Herzinfarkt Nachrichten

Die Nahrungsaufnahme auf wenige Stunden am Tag zu beschränken, hat möglicherweise einen günstigen Einfluss auf die Prognose nach akutem ST-Hebungsinfarkt. Darauf deutet eine Studie an der Uniklinik in Halle an der Saale hin.

Klimaschutz beginnt bei der Wahl des Inhalators

14.05.2024 Klimawandel Podcast

Auch kleine Entscheidungen im Alltag einer Praxis können einen großen Beitrag zum Klimaschutz leisten. Die neue Leitlinie zur "klimabewussten Verordnung von Inhalativa" geht mit gutem Beispiel voran, denn der Wechsel vom klimaschädlichen Dosieraerosol zum Pulverinhalator spart viele Tonnen CO₂. Leitlinienautor PD Dr. Guido Schmiemann erklärt, warum nicht nur die Umwelt, sondern auch Patientinnen und Patienten davon profitieren.

Typ-2-Diabetes und Depression folgen oft aufeinander

14.05.2024 Typ-2-Diabetes Nachrichten

Menschen mit Typ-2-Diabetes sind überdurchschnittlich gefährdet, in den nächsten Jahren auch noch eine Depression zu entwickeln – und umgekehrt. Besonders ausgeprägt ist die Wechselbeziehung laut GKV-Daten bei jüngeren Erwachsenen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2022

Monogenic lupus with homozygous C4A deficiency presenting as bronchiectasis and immune-mediated thrombocytopenia

The impact of Sjӧgren’s syndrome on the quality of sexual life of female patients in the UK: a controlled analysis

Screening for latent tuberculosis before starting TNF-alpha inhibitors in a population with high BCG vaccination rates

Catatonia in systemic lupus erythematosus: case based review

Nailfold capillaroscopy changes associated with anti-RNP antibodies in systemic lupus erythematosus