Reduced expressions of apoptosis-related proteins TRAIL, Bcl-2, and TNFR1 in NK cells of juvenile-onset systemic lupus erythematosus patients: relations with disease activity, nephritis, and neuropsychiatric involvement

Nenhuma Miniatura disponível
Citações na Scopus
0
Tipo de produção
article
Data de publicação
2024
DOI
Scopus
Web of Science
PubMed
Dimensions
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Autores
Citação
FRONTIERS IN IMMUNOLOGY, v.15, article ID 1327255, 10p, 2024
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement.Methods Thirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3-CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels.Results Patients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = -0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls.Conclusion This study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell-based.
Palavras-chave
anti-dsDNA, apoptosis, Bcl-2, Juvenile SLE, NK cells, nephritis, SLEDAI-2K score, TRAIL
URI
https://observatorio.fm.usp.br/handle/OPI/76999
Referências
  1. BOHAN A, 1975, NEW ENGL J MED, V292, P344, DOI 10.1056/NEJM197502132920706
  2. Carneiro-Sampaio M, 2008, J CLIN IMMUNOL, V28, pS34, DOI 10.1007/s10875-008-9187-2
  3. Cui JH, 2012, J NEPHROL, V25, P255, DOI 10.5301/JN.2011.8451
  4. El-Karaksy SM, 2013, GENE, V527, P211, DOI 10.1016/j.gene.2013.05.084
  5. Eneslätt K, 2001, J CLIN IMMUNOL, V21, P183, DOI 10.1023/A:1011035115342
  6. ErkellerYuksel FM, 1997, LUPUS, V6, P708, DOI 10.1177/096120339700600905
  7. Gladman DD, 2002, J RHEUMATOL, V29, P288
  8. Gomes RC, 2016, ARTHRIT CARE RES, V68, P1736, DOI 10.1002/acr.22881
  9. Henriques A, 2013, CLIN RHEUMATOL, V32, P805, DOI 10.1007/s10067-013-2176-8
  10. Herrmann M, 1998, ARTHRITIS RHEUM-US, V41, P1241, DOI 10.1002/1529-0131(199807)41:7<1241::AID-ART15>3.0.CO;2-H
  11. Hochberg MC, 1997, ARTHRITIS RHEUM, V40, P1725, DOI 10.1002/art.1780400928
  12. Hughes P, 2006, CURR DIRECT AUTOIMMU, V9, P74
  13. Jesus AA, 2011, LUPUS, V20, P1275, DOI 10.1177/0961203311411598
  14. Jung JY, 2015, INT J RHEUM DIS, V18, P294, DOI 10.1111/1756-185X.12568
  15. Li Taotao, 2020, Clin Exp Rheumatol, V38 Suppl 124, P84
  16. Liphaus BL, 2013, LUPUS, V22, P940, DOI 10.1177/0961203313496300
  17. Liphaus BL, 2006, CLIN DEV IMMUNOL, V13, P283, DOI 10.1080/17402520600877786
  18. Liphaus BL, 2020, ANN RHEUM DIS, V79, P427, DOI 10.1136/annrheumdis-2019-216410
  19. Liphaus BL, 2020, CLIN RHEUMATOL, V39, P509, DOI 10.1007/s10067-019-04799-5
  20. Liphaus BL, 2017, CLIN RHEUMATOL, V36, P2847, DOI 10.1007/s10067-017-3615-8
  21. Liphaus BL, 2015, CLINICS, V70, P220, DOI 10.6061/clinics/2015(03)12
  22. Liphaus BL, 2010, CLINICS, V65, P327, DOI 10.1590/S1807-59322010000300014
  23. Liphaus BL, 2007, J RHEUMATOL, V34, P1580
  24. Midgley A, 2009, ARTHRITIS RHEUM, V60, P2390, DOI 10.1002/art.24634
  25. Munoz LE, 2008, LUPUS, V17, P371, DOI 10.1177/0961203308089990
  26. Ortaldo JR, 1997, J LEUKOCYTE BIOL, V61, P209, DOI 10.1002/jlb.61.2.209
  27. Park YW, 2009, ARTHRITIS RHEUM-US, V60, P1753, DOI 10.1002/art.24556
  28. Petri M, 2012, ARTHRITIS RHEUM-US, V64, P2677, DOI 10.1002/art.34473
  29. Ramírez-Labrada A, 2022, FRONT IMMUNOL, V13, DOI 10.3389/fimmu.2022.896228
  30. Rus V, 2005, CLIN IMMUNOL, V117, P48, DOI 10.1016/j.clim.2005.05.001
  31. Smith EMD., 2022, Curr Opin Rheumatol, V34, P1
  32. Smith EMD, 2019, CLIN IMMUNOL, V209, DOI 10.1016/j.clim.2019.108274
  33. Takahashi K, 2001, J CLIN INVEST, V107, pR23, DOI 10.1172/JCI11819
  34. TAKEDA K, 1993, J EXP MED, V177, P155, DOI 10.1084/jem.177.1.155
  35. Yabuhara A, 1996, J RHEUMATOL, V23, P171
  36. Yang YY, 2021, CLIN TRANSL IMMUNOL, V10, DOI 10.1002/cti2.1250
  37. Zahran AM, 2019, ARCH IMMUNOL THER EX, V67, P161, DOI 10.1007/s00005-019-00537-6

Coleções
Artigos e Materiais de Revistas Científicas - FM/MPE