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Rheumatology International

Erschienen in:

20.05.2022 | Review

Age-related immunosenescence in Behçet’s disease

verfasst von: Döndü Üsküdar Cansu, Cengiz Korkmaz

Erschienen in: Rheumatology International | Ausgabe 9/2022

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Abstract

Behçet’s disease (BD) is a systemic vasculitis of unknown etiology causing recurrent mucocutaneous lesions, ocular involvement, central nervous system involvement, and vascular involvement. The disease is characterized by exacerbations and spontaneous remissions. Prognosis is poor in young men when the vessels are involved. The course is more active and severe in the first years of the disease. One of the most interesting features of BD is that the disease changes to a state of low activity and remission over time. Although the association between aging and lower disease activity is well established, there is limited literature data and research investigating the cause. Similarly, there are not many studies on the late onset of BD and its characteristics. In this regard, understanding the cause of the decline in disease activity over time may open new avenues for pathogenesis and treatment research. In this review, we focus on the immunosenescence caused by chronic inflammation and aging in BD. Based on the effect of testosterone on innate immune cells, we also briefly discussed the potential effects of this hormone on vascular involvement.

Yazici Y, Hatemi G, Bodaghi B, Cheon JH, Suzuki N, Ambrose N, Yazici H (2021) Behçet syndrome. Nat Rev Dis Primers 7(1):67. https://doi.org/10.1038/s41572-021-00301-1CrossRefPubMed

Seyahi E (2019) Phenotypes in Behcet’s syndrome. Intern Emerg Med 14(5):677–689. https://doi.org/10.1007/s11739-019-02046-yCrossRefPubMed

Yazici H, Seyahi E, Hatemi G, Yazici Y (2018) Behçet syndrome: a contemporary view. Nat Rev Rheumatol 14(2):107–119. https://doi.org/10.1038/nrrheum.2017.208CrossRefPubMed

Emmi G, Bettiol A, Silvestri E, Di Scala G, Becatti M, Fiorillo C, Prisco D (2019) Vascular Behçet’s syndrome: an update. Intern Emerg Med 14(5):645–652. https://doi.org/10.1007/s11739-018-1991-yCrossRefPubMed

Mattioli I, Bettiol A, Saruhan-Direskeneli G, Direskeneli H, Emmi G (2021) Pathogenesis of Behçet’s syndrome: genetic. Environ Immunol Factors Front Med (Lausanne) 8:713052. https://doi.org/10.3389/fmed.2021.713052CrossRef

van der Houwen TB, van Hagen PM, van Laar JAM (2022) Immunopathogenesis of Behcet’s disease and treatment modalities. Semin Arthritis Rheum 52:151956. https://doi.org/10.1016/j.semarthrit.2022.151956CrossRefPubMed

Seyahi E (2020) Venous involvement in inflammatory disorders. Curr Opin Rheumatol 32(1):29–34. https://doi.org/10.1097/BOR.0000000000000670CrossRefPubMed

Khan E, Ambrose NL, Ahnström J, Kiprianos AP, Stanford MR, Eleftheriou D, Brogan PA, Mason JC, Johns M, Laffan MA, Haskard DO (2016) A low balance between microparticles expressing tissue factor pathway inhibitor and tissue factor is associated with thrombosis in Behçet’s syndrome. Sci Rep 6:38104. https://doi.org/10.1038/srep38104CrossRefPubMedPubMedCentral

Emmi G, Becatti M, Bettiol A, Hatemi G, Prisco D, Fiorillo C (2019) Behçet’s syndrome as a model of thrombo-inflammation: the role of neutrophils. Front Immunol 14(10):1085. https://doi.org/10.3389/fimmu.2019.01085CrossRef

10.

de Vargas RM, da Cruz MLN, Giarllarielli MPH, Sano BM, da Silva GI, Zoccal KF, Tefé-Silva C (2021) Vascular involvement in Behçet’s disease: the immunopathological process. J Vasc Bras 20:e20200170. https://doi.org/10.1590/1677-5449.200170CrossRefPubMedPubMedCentral

11.

Kara Kivanc B, Gönüllü E, Akay OM, Ertürk A, Bal C, Cansu DÜ, Korkmaz C (2018) Why are male patients with Behçet’s disease prone to thrombosis? A rotational thromboelastographic analysis. Clin Exp Rheumatol 36(6 Suppl 115):63–67PubMed

12.

Alibaz-Oner F, Karadeniz A, Ylmaz S, Balkarl A, Kimyon G, Yazc A, Çnar M, Ylmaz S, Yldz F, Bilge ŞY, Bilgin E, Coskun BN, Omma A, Çetin GY, Çağatay Y, Karaaslan Y, Sayarloğlu M, Pehlivan Y, Kalyoncu U, Karadağ Ö, Kaşifoğlu T, Erken E, Pay S, Çefle A, Ksack B, Onat AM, Çobankara V, Direskeneli H (2015) Behçet disease with vascular involvement: effects of different therapeutic regimens on the incidence of new relapses. Medicine (Baltimore) 94(6):e494. https://doi.org/10.1097/MD.0000000000000494CrossRef

13.

Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254. https://doi.org/10.1111/j.1749-6632.2000.tb06651.xCrossRefPubMed

14.

Franceschi C, Salvioli S, Garagnani P, de Eguileor M, Monti D, Capri M (2017) Immunobiography and the heterogeneity of immune responses in the elderly: a focus on inflammaging and trained immunity. Front Immunol 8:982. https://doi.org/10.3389/fimmu.2017.00982CrossRefPubMedPubMedCentral

15.

Seidler S, Zimmermann HW, Bartneck M, Trautwein C, Tacke F (2010) Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults. BMC Immunol 11:30. https://doi.org/10.1186/1471-2172-11-30CrossRefPubMedPubMedCentral

16.

Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, Chen S, Towle V, Belshe RB, Fikrig E, Allore HG, Montgomery RR, Shaw AC (2010) Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol 184(5):2518–2527. https://doi.org/10.4049/jimmunol.0901022CrossRefPubMed

17.

Qian F, Wang X, Zhang L, Chen S, Piecychna M, Allore H, Bockenstedt L, Malawista S, Bucala R, Shaw AC, Fikrig E, Montgomery RR (2012) Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderly. Aging Cell 11(1):104–110. https://doi.org/10.1111/j.1474-9726.2011.00759.xCrossRefPubMed

18.

Metcalf TU, Wilkinson PA, Cameron MJ, Ghneim K, Chiang C, Wertheimer AM, Hiscott JB, Nikolich-Zugich J, Haddad EK (2017) Human monocyte subsets are transcriptionally and functionally altered in aging in response to pattern recognition receptor agonists. J Immunol 199(4):1405–1417. https://doi.org/10.4049/jimmunol.1700148CrossRefPubMed

19.

Simell B, Vuorela A, Ekström N, Palmu A, Reunanen A, Meri S, Käyhty H, Väkeväinen M (2011) Aging reduces the functionality of anti-pneumococcal antibodies and the killing of streptococcus pneumoniae by neutrophil phagocytosis. Vaccine 29(10):1929–1934. https://doi.org/10.1016/j.vaccine.2010.12.121CrossRefPubMed

20.

Butcher S, Chahal H, Savey E, Killampalli VV, Alpar EK, Lord JM (2001) Functional decline in human neutrophils with age. Sci World J 1:67. https://doi.org/10.1100/TSW.2001.105.eCollection2001CrossRef

21.

Wenisch C, Patruta S, Daxböck F, Krause R, Hörl W (2000) Effect of age on human neutrophil function. J Leukoc Biol 67(1):40–45. https://doi.org/10.1002/jlb.67.1.40CrossRefPubMed

22.

Fulop T, Larbi A, Douziech N, Fortin C, Guérard KP, Lesur O, Khalil A, Dupuis G (2004) Signal transduction and functional changes in neutrophils with aging. Aging Cell 3(4):217–226. https://doi.org/10.1111/j.1474-9728.2004.00110.xCrossRefPubMed

23.

Ortmann W, Kolaczkowska E (2018) Age is the work of art? Impact of neutrophil and organism age on neutrophil extracellular trap formation. Cell Tissue Res 371(3):473–488. https://doi.org/10.1007/s00441-017-2751-4CrossRefPubMed

24.

Fagiolo U, Cossarizza A, Scala E, Fanales-Belasio E, Ortolani C, Cozzi E, Monti D, Franceschi C, Paganelli R (1993) Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol 23(9):2375–2378. https://doi.org/10.1002/eji.1830230950CrossRefPubMed

25.

McLaughlin ME, Kao R, Liener IE, Hoidal JR (1986) A quantitative in vitro assay of polymorphonuclear leukocyte migration through human amnion membrane utilizing 111in-oxine. J Immunol Methods 95(1):89–98. https://doi.org/10.1016/0022-1759(86)90321-2CrossRefPubMed

26.

de Gonzalo-Calvo D, Neitzert K, Fernández M, Vega-Naredo I, Caballero B, García-Macía M, Suárez FM, Rodríguez-Colunga MJ, Solano JJ, Coto-Montes A (2010) Differential inflammatory responses in aging and disease: TNF-alpha and IL-6 as possible biomarkers. Free Radic Biol Med 49(5):733–737. https://doi.org/10.1016/j.freeradbiomed.2010.05.019CrossRefPubMed

27.

Gerli R, Monti D, Bistoni O, Mazzone AM, Peri G, Cossarizza A, Di Gioacchino M, Cesarotti ME, Doni A, Mantovani A, Franceschi C, Paganelli R (2000) Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians. Mech Ageing Dev 121(1–3):37–46. https://doi.org/10.1016/s0047-6374(00)00195-0CrossRefPubMed

28.

Morrisette-Thomas V, Cohen AA, Fülöp T, Riesco É, Legault V, Li Q, Milot E, Dusseault-Bélanger F, Ferrucci L (2014) Inflamm-aging does not simply reflect increases in pro-inflammatory markers. Mech Ageing Dev 139:49–57. https://doi.org/10.1016/j.mad.2014.06.005CrossRefPubMedPubMedCentral

29.

Le Garff-Tavernier M, Béziat V, Decocq J, Siguret V, Gandjbakhch F, Pautas E, Debré P, Merle-Beral H, Vieillard V (2010) Human NK cells display major phenotypic and functional changes over the life span. Aging Cell 9(4):527–535. https://doi.org/10.1111/j.1474-9726.2010.00584.xCrossRefPubMed

30.

Kared H, Martelli S, Ng TP, Pender SL, Larbi A (2016) CD57 in human natural killer cells and T-lymphocytes. Cancer Immunol Immunother 65(4):441–452. https://doi.org/10.1007/s00262-016-1803-zCrossRefPubMed

31.

Huntington ND, Tabarias H, Fairfax K, Brady J, Hayakawa Y, Degli-Esposti MA, Smyth MJ, Tarlinton DM, Nutt SL (2007) NK cell maturation and peripheral homeostasis is associated with KLRG1 up-regulation. J Immunol 178(8):4764–4770. https://doi.org/10.4049/jimmunol.178.8.4764CrossRefPubMed

32.

Gomez I, Marx F, Gould EA, Grubeck-Loebenstein B (2004) T cells from elderly persons respond to neoantigenic stimulation with an unimpaired IL-2 production and an enhanced differentiation into effector cells. Exp Gerontol 39(4):597–605. https://doi.org/10.1016/j.exger.2003.11.018CrossRefPubMed

33.

Kverneland AH, Streitz M, Geissler E, Hutchinson J, Vogt K, Boës D, Niemann N, Pedersen AE, Schlickeiser S, Sawitzki B (2016) Age and gender leucocytes variances and reference values were generated using the standardized ONE-Study protocol. Cytometry A 89(6):543–564. https://doi.org/10.1002/cyto.a.22855CrossRefPubMed

34.

Schmitt V, Rink L, Uciechowski P (2013) The Th17/Treg balance is disturbed during aging. Exp Gerontol 48(12):1379–1386. https://doi.org/10.1016/j.exger.2013.09.003CrossRefPubMed

35.

Hoffman W, Lakkis FG, Chalasani G (2016) B cells, antibodies, and more. Clin J Am Soc Nephrol 11(1):137–154. https://doi.org/10.2215/CJN.09430915CrossRefPubMed

36.

Pritz T, Lair J, Ban M, Keller M, Weinberger B, Krismer M, Grubeck-Loebenstein B (2015) Plasma cell numbers decrease in bone marrow of old patients. Eur J Immunol 45(3):738–746. https://doi.org/10.1002/eji.201444878CrossRefPubMed

37.

Rodriguez-Zhurbenko N, Quach TD, Hopkins TJ, Rothstein TL, Hernandez AM (2019) Human B-1 cells and B-1 cell antibodies change with advancing age. Front Immunol 10:483. https://doi.org/10.3389/fimmu.2019.00483CrossRefPubMedPubMedCentral

38.

Naradikian MS, Hao Y, Cancro MP (2016) Age-associated B cells: key mediators of both protective and autoreactive humoral responses. Immunol Rev 269(1):118–129. https://doi.org/10.1111/imr.12380CrossRefPubMed

39.

Cansu DÜ, Kaşifoğlu T, Korkmaz C (2016) Do clinical findings of Behçet’s disease vary by gender? A single-center experience from 329 patients. Eur J Rheumatol 3(4):157–160. https://doi.org/10.5152/eurjrheum.2016.038CrossRefPubMedPubMedCentral

40.

Zou J, Luo JF, Shen Y, Guan JL (2021) Distinct clinical characteristics of pediatric Behçet’s syndrome: a study from a referral center in China. Mod Rheumatol 31(6):1158–1163. https://doi.org/10.1080/14397595.2021.1891670CrossRefPubMed

41.

Sungur G, Hazirolan D, Hekimoglu E, Kasim R, Duman S (2010) Late-onset Behçet’s disease: demographic, clinical, and ocular features. Graefes Arch Clin Exp Ophthalmol 248(9):1325–1330. https://doi.org/10.1007/s00417-010-1399-5CrossRefPubMed

42.

Güzelant Özköse G (2020) Late-Onset Behçet’s Disease. In: Seyahi E (ed) Behçet’s disease. 1st edn. Türkiye Klinikleri, Ankara, pp 85–88

43.

Kural-Seyahi E, Fresko I, Seyahi N, Ozyazgan Y, Mat C, Hamuryudan V, Yurdakul S, Yazici H (2003) The long-term mortality and morbidity of Behçet syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center. Medicine (Baltimore) 82(1):60–76. https://doi.org/10.1097/00005792-200301000-00006CrossRef

44.

David E, Fauvernier M, Saadoun D, Gerfaud-Valentin M, Maurcort-Boulch D, Sève P, Jamilloux Y (2022) Mortality associated with Behçet’s disease in France assessed by multiple-cause-of-death analysis. Clin Rheumatol. https://doi.org/10.1007/s10067-021-06027-5CrossRefPubMed

45.

Yang JY, Park MJ, Park S, Lee ES (2018) Increased senescent CD8+ T cells in the peripheral blood mononuclear cells of Behçet’s disease patients. Arch Dermatol Res 310(2):127–138. https://doi.org/10.1007/s00403-017-1802-8CrossRefPubMed

46.

Kalim H, Pratama MZ, Mahardini E, Winoto ES, Krisna PA, Handono K (2020) Accelerated immune aging was correlated with lupus-associated brain fog in reproductive-age systemic lupus erythematosus patients. Int J Rheum Dis 23(5):620–626. https://doi.org/10.1111/1756-185X.13816CrossRefPubMed

47.

Pawlik A, Ostanek L, Brzosko I, Brzosko M, Masiuk M, Machalinski B, Gawronska-Szklarz B (2003) The expansion of CD4+CD28- T cells in patients with rheumatoid arthritis. Arthritis Res Ther 5(4):R210–R213. https://doi.org/10.1186/ar766CrossRefPubMedPubMedCentral

48.

Chalan P, van den Berg A, Kroesen BJ, Brouwer L, Boots A (2015) Rheumatoid arthritis, immunosenescence and the hallmarks of aging. Curr Aging Sci 8(2):131–146. https://doi.org/10.2174/1874609808666150727110744CrossRefPubMedPubMedCentral

49.

Zajac AJ, Blattman JN, Murali-Krishna K, Sourdive DJ, Suresh M, Altman JD, Ahmed R (1998) Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med 188(12):2205–2213. https://doi.org/10.1084/jem.188.12.2205CrossRefPubMedPubMedCentral

50.

McKinney EF, Smith KG (2016) T cell exhaustion and immune-mediated disease-the potential for therapeutic exhaustion. Curr Opin Immunol 43:74–80. https://doi.org/10.1016/j.coi.2016.09.005CrossRefPubMed

51.

Zhao Y, Shao Q, Peng G (2020) Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment. Cell Mol Immunol 17(1):27–35. https://doi.org/10.1038/s41423-019-0344-8CrossRefPubMed

52.

Young A, Quandt Z, Bluestone JA (2018) The balancing act between cancer immunity and autoimmunity in response to immunotherapy. Cancer Immunol Res 6(12):1445–1452. https://doi.org/10.1158/2326-6066.CIR-18-0487CrossRefPubMedPubMedCentral

53.

McKinney EF, Lee JC, Jayne DR, Lyons PA, Smith KG (2015) T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature 523(7562):612–616. https://doi.org/10.1038/nature14468CrossRefPubMedPubMedCentral

54.

Okazaki T, Okazaki IM, Wang J, Sugiura D, Nakaki F, Yoshida T, Kato Y, Fagarasan S, Muramatsu M, Eto T, Hioki K, Honjo T (2011) PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice. J Exp Med 208(2):395–407. https://doi.org/10.1084/jem.20100466CrossRefPubMedPubMedCentral

55.

Lowe GD, Rumley A, Woodward M, Morrison CE, Philippou H, Lane DA, Tunstall-Pedoe H (1997) Epidemiology of coagulation factors, inhibitors and activation markers: the third glasgow MONICA survey. I. Illustrative reference ranges by age, sex and hormone use. Br J Haematol 97(4):775–84. https://doi.org/10.1046/j.1365-2141.1997.1222936CrossRefPubMed

56.

Esmon CT (2009) Basic mechanisms and pathogenesis of venous thrombosis. Blood Rev 23(5):225–229. https://doi.org/10.1016/j.blre.2009.07.002CrossRefPubMedPubMedCentral

57.

La Regina M, Gasparyan AY, Orlandini F, Prisco D (2010) Behçet’s disease as a model of venous thrombosis. Open Cardiovasc Med J 4:71–77. https://doi.org/10.2174/1874192401004020071CrossRefPubMedPubMedCentral

58.

Silverstein RL, Bauer KA, Cushman M, Esmon CT, Ershler WB, Tracy RP (2007) Venous thrombosis in the elderly: more questions than answers. Blood 110(9):3097–3101. https://doi.org/10.1182/blood-2007-06-096545CrossRefPubMed

59.

Yavuz S, Ozilhan G, Elbir Y, Tolunay A, Eksioglu-Demiralp E, Direskeneli H (2007) Activation of neutrophils by testosterone in Behcet’s disease. Clin Exp Rheumatol 25(4 Suppl 45):S46-51PubMed

60.

Adams MR, Pijut KD, Uttal-Veroff KC, Davis GA (2022) Acute portal and superior mesenteric vein thrombosis with topical testosterone therapy: an adverse drug event case report. J Pharm Pract. https://doi.org/10.1177/08971900211073286CrossRefPubMedPubMedCentral

Titel: Age-related immunosenescence in Behçet’s disease
verfasst von: Döndü Üsküdar Cansu
Cengiz Korkmaz
Publikationsdatum: 20.05.2022
Verlag: Springer Berlin Heidelberg
Erschienen in: Rheumatology International / Ausgabe 9/2022
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-022-05144-x

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