Irmeli Roine1, Tuula Pelkonen, Luis Bernardino, Anneli Lauhio, Taina Tervahartiala, Maija Lappalainen, Matti Kataja, Anne Pitkäranta, Timo Sorsa, Heikki Peltola. 1. From the *Faculty of Medicine, University Diego Portales, Santiago, Chile; †David Bernardino Children's Hospital, Luanda, Angola; ‡Children´s Hospital; §Division of Infectious Diseases, Department of Medicine; ¶Department of Oral and Maxillofacial Diseases; ‖Department of Virology and Immunology, Laboratory Services (HUSLAB), Helsinki University Central Hospital; **National Institute for Health and Welfare; ††Institute of Clinical Medicine; ‡‡Department of Otorhinolaryngology, Helsinki University Central Hospital; and §§Institute of Dentistry, University of Helsinki, Helsinki, Finland.
Abstract
BACKGROUND: Increased concentrations of matrix metalloproteinases (MMP) in cerebrospinal fluid are part of the host response in bacterial meningitis (BM). We investigated whether the concentrations of MMP-9 and the tissue inhibitor of metalloproteinase (TIMP)-1 predict the outcome in childhood BM. METHODS: Cerebrospinal fluid MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were quantified by an enzyme-linked immunosorbent assay from 264 and 335 patients, respectively; 43 children without BM served as controls. The results were compared with previously known independent predictors of death and sequelae. RESULTS: Higher MMP-9 and TIMP-1 values distinguished the controls from the BM patients (P < 0.0001). A MMP-9 concentration >940 ng/mL proved an independent predictor of death [adjusted odds ratio: 4.03; 95% confidence interval (CI): 2.09-7.77; P < 0.0001]. If the patient additionally presented with a Glasgow Coma Score below 9, the odds increased to 13.21 (95% CI: 5.44-32.08; P < 0.0001). TIMP-1 levels correlated with the severity of sequelae (ρ: 0.30; P < 0.0001), but not with death. Its concentration above 390 ng/mL increased the likelihood of sequelae 3.43-fold (95% CI: 1·73-6·79; P = 0.0004), and up to 31.18-fold (95% CI: 4.05-239.8; P = 0.0009) if the patient also presented a Glasgow Coma Score < 12. CONCLUSIONS: Elevated cerebrospinal fluid MMP-9 and TIMP-1 values predict 2 important outcomes in childhood BM. Combined with a clinical evaluation, quantification of these indices augments the chances to identify the patients in greatest need of better treatment modalities.
BACKGROUND: Increased concentrations of matrix metalloproteinases (MMP) in cerebrospinal fluid are part of the host response in bacterial meningitis (BM). We investigated whether the concentrations of MMP-9 and the tissue inhibitor of metalloproteinase (TIMP)-1 predict the outcome in childhood BM. METHODS: Cerebrospinal fluid MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were quantified by an enzyme-linked immunosorbent assay from 264 and 335 patients, respectively; 43 children without BM served as controls. The results were compared with previously known independent predictors of death and sequelae. RESULTS: Higher MMP-9 and TIMP-1 values distinguished the controls from the BM patients (P < 0.0001). A MMP-9 concentration >940 ng/mL proved an independent predictor of death [adjusted odds ratio: 4.03; 95% confidence interval (CI): 2.09-7.77; P < 0.0001]. If the patient additionally presented with a Glasgow Coma Score below 9, the odds increased to 13.21 (95% CI: 5.44-32.08; P < 0.0001). TIMP-1 levels correlated with the severity of sequelae (ρ: 0.30; P < 0.0001), but not with death. Its concentration above 390 ng/mL increased the likelihood of sequelae 3.43-fold (95% CI: 1·73-6·79; P = 0.0004), and up to 31.18-fold (95% CI: 4.05-239.8; P = 0.0009) if the patient also presented a Glasgow Coma Score < 12. CONCLUSIONS: Elevated cerebrospinal fluid MMP-9 and TIMP-1 values predict 2 important outcomes in childhood BM. Combined with a clinical evaluation, quantification of these indices augments the chances to identify the patients in greatest need of better treatment modalities.
Authors: Emma C Wall; Philip Brownridge; Gavin Laing; Vanessa S Terra; Veronica Mlozowa; Brigitte Denis; Mulinda Nyirenda; Theresa Allain; Elisa Ramos-Sevillano; Enitan Carrol; Andrea Collins; Stephen B Gordon; David G Lalloo; Brendan Wren; Robert Beynon; Robert S Heyderman; Jeremy S Brown Journal: Front Cell Infect Microbiol Date: 2020-12-11 Impact factor: 5.293