Neutrophil extracellular traps are a source of extracellular HMGB1 in lupus nephritis: associations with clinical and histopathological features
Por:
Whittall-Garcia, L. P., Torres-Ruiz, J., Zentella-Dehesa, A., Tapia-Rodriguez, M., Alcocer-Varela, J., Mendez-Huerta, N., Gomez-Martin, D.
Publicada:
1 nov 2019
Ahead of Print:
1 oct 2019
Categoría:
Rheumatology
Resumen:
Objective This study aimed to analyze the expression of the high
mobility group box-1 (HMGB1) protein in neutrophil extracellular traps
(NETs) of patients with lupus nephritis (LN) and its association with
clinical and histopathological features of the disease.
Methods Twenty-three patients with biopsy-confirmed LN and 14 systemic
lupus erythematosus (SLE) patients with active disease (SLE Disease
Activity Index (SLEDAI) score >= 6) and no evidence of LN were included.
Clinical and laboratory features were recorded. NETs and the expression
of HMGB1 were assessed by confocal microscopy, and serum HMGB1 levels
were measured by ELISA.
Results In comparison to patients without kidney disease, patients with
LN had a higher expression of HMGB1 in spontaneous (57 vs. 30.4; p =
0.027) and lipopolysaccharide (LPS)-induced (55.8 vs. 24.9; p = 0.005)
NETs. We found a positive correlation between serum HMGB1 and the
expression of HMGB1 in LPS-induced NETs (r = 0.447, p = 0.017). The
expression of HMGB1 in spontaneous NETs correlated with SLEDAI score (r
= 0.514, p = 0.001), anti-dsDNA antibodies (r = 0.467, p = 0.004), the
rate of glomerular filtration descent (r = 0.543, p = 0.001), and
diverse histopathological components of active nephritis in the kidney
biopsy, such as the activity index (r = 0.581, p = 0.004), fibrinoid
necrosis (r = 0.603, p = 0.002), and cellular crescents (r = 0.486, p =
0.019).
Conclusions In patients with SLE, NETs are a source of extracellular
HMGB1. The expression of HMGB1 in NETs is higher among patients with LN,
which correlates with clinical and histopathological features of active
nephritis and suggest a possible role of this alarmin in the
pathophysiology of kidney damage in SLE.
Filiaciones:
Whittall-Garcia, L. P.:
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City, DF, Mexico
Torres-Ruiz, J.:
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Emergency Medicine Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City, DF, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Emergency Med Dept, Mexico City, DF, Mexico
Zentella-Dehesa, A.:
Department of Genomic Medicine and Environmental Toxicology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Genom Med & Environm Toxicol, Mexico City, DF, Mexico
Tapia-Rodriguez, M.:
Microscopy Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Microscopy Unit, Mexico City, DF, Mexico
Alcocer-Varela, J.:
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City, DF, Mexico
Mendez-Huerta, N.:
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City, DF, Mexico
Gomez-Martin, D.:
Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico
Flow Cytometry Unit, Red de Apoyo a la Investigación. Coordinación de Investigación Científica, Universidad Nacional Autónoma de México, Mexico City, Mexico
Tecnol Monterrey, Escuela Med & Ciencias Salud, Ave Morones Prieto 3000, Monterrey 64710, Mexico
Univ Nacl Autonoma Mexico, Flow Cytometry Unit, Red Apoyo Invest, Coordinat Invest Cient, Mexico City, DF, Mexico
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