Biomarkers for prediction of skeletal disease progression in mucopolysaccharidosis type I
Abstract Background Orthopedic disease progresses in mucopolysaccharidosis type I (MPS I), even with approved therapies and remains a major factor in persistent suffering and disability. Novel therapies and accurate predictors of response are needed. The primary objective of this study was to identi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-03-01
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| Series: | JIMD Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jmd2.12190 |
| _version_ | 1818368855985094656 |
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| author | Troy C. Lund Terence M. Doherty Julie B. Eisengart Rebecca L. Freese Kyle D. Rudser Ellen B. Fung Bradley S. Miller Klane K. White Paul J. Orchard Chester B. Whitley Lynda E. Polgreen |
| author_facet | Troy C. Lund Terence M. Doherty Julie B. Eisengart Rebecca L. Freese Kyle D. Rudser Ellen B. Fung Bradley S. Miller Klane K. White Paul J. Orchard Chester B. Whitley Lynda E. Polgreen |
| author_sort | Troy C. Lund |
| collection | DOAJ |
| description | Abstract Background Orthopedic disease progresses in mucopolysaccharidosis type I (MPS I), even with approved therapies and remains a major factor in persistent suffering and disability. Novel therapies and accurate predictors of response are needed. The primary objective of this study was to identify surrogate biomarkers of future change in orthopedic disease. Methods As part of a 9‐year observational study of MPS I, range‐of‐motion (ROM), height, pelvic radiographs were measured annually. Biomarkers in year 1 were compared to healthy controls. Linear regression tested for associations of change in biomarkers over the first year with change in long‐term outcomes. Results MPS I participants (N = 19) were age 5 to 16 years and on average 6.9 ± 2.9 years post treatment initiation. Healthy controls (N = 51) were age 9 to 17 years. Plasma IL‐1β, TNF‐α, osteocalcin, pyridinolines, and deoxypyridinolines were higher in MPS than controls. Within MPS, progression of hip dysplasia was present in 46% to 77%. A 1 pg/mL increase in IL‐6 was associated with −22°/year change in ROM (−28 to −15; P < .001), a 20 nmol/mmol creatinine/year increase in urine PYD was associated with a −0.024 Z‐score/year change in height Z‐score (−0.043 to −0.005; P = .016), and a 20 nmol/mmol creatinine/year increase in urine PYD was associated with a −2.0%/year change in hip dysplasia measured by Reimers migration index (−3.8 to −0.1; P = .037). Conclusions Inflammatory cytokines are high in MPS I. IL‐6 and PYD were associated with progression in joint contracture, short stature, and hip dysplasia over time. Once validated, these biomarkers may prove useful for predicting response to treatment of skeletal disease in MPS I. |
| first_indexed | 2024-12-13T23:14:35Z |
| format | Article |
| id | doaj.art-eda272a015ff42afbdfa8b995f7872ed |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-12-13T23:14:35Z |
| publishDate | 2021-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-eda272a015ff42afbdfa8b995f7872ed2022-12-21T23:28:00ZengWileyJIMD Reports2192-83122021-03-01581899910.1002/jmd2.12190Biomarkers for prediction of skeletal disease progression in mucopolysaccharidosis type ITroy C. Lund0Terence M. Doherty1Julie B. Eisengart2Rebecca L. Freese3Kyle D. Rudser4Ellen B. Fung5Bradley S. Miller6Klane K. White7Paul J. Orchard8Chester B. Whitley9Lynda E. Polgreen10Department of Pediatrics University of Minnesota Minneapolis Minnesota USADepartment of Pediatrics The Lundquist Institute at Harbor‐UCLA Medical Center Torrance California USADepartment of Pediatrics University of Minnesota Minneapolis Minnesota USABiostatistical Design and Analysis Center, Clinical and Translational Science Institute University of Minnesota Minneapolis Minnesota USASchool of Public Health, Division of Biostatistics University of Minnesota Minneapolis Minnesota USADepartment of Hematology University of California, San Francisco Benioff Children's Hospital Oakland California USADepartment of Pediatrics University of Minnesota Minneapolis Minnesota USADepartment of Orthopaedics and Sports Medicine Seattle Children's Hospital Seattle Washington USADepartment of Pediatrics University of Minnesota Minneapolis Minnesota USADepartment of Pediatrics University of Minnesota Minneapolis Minnesota USADepartment of Pediatrics The Lundquist Institute at Harbor‐UCLA Medical Center Torrance California USAAbstract Background Orthopedic disease progresses in mucopolysaccharidosis type I (MPS I), even with approved therapies and remains a major factor in persistent suffering and disability. Novel therapies and accurate predictors of response are needed. The primary objective of this study was to identify surrogate biomarkers of future change in orthopedic disease. Methods As part of a 9‐year observational study of MPS I, range‐of‐motion (ROM), height, pelvic radiographs were measured annually. Biomarkers in year 1 were compared to healthy controls. Linear regression tested for associations of change in biomarkers over the first year with change in long‐term outcomes. Results MPS I participants (N = 19) were age 5 to 16 years and on average 6.9 ± 2.9 years post treatment initiation. Healthy controls (N = 51) were age 9 to 17 years. Plasma IL‐1β, TNF‐α, osteocalcin, pyridinolines, and deoxypyridinolines were higher in MPS than controls. Within MPS, progression of hip dysplasia was present in 46% to 77%. A 1 pg/mL increase in IL‐6 was associated with −22°/year change in ROM (−28 to −15; P < .001), a 20 nmol/mmol creatinine/year increase in urine PYD was associated with a −0.024 Z‐score/year change in height Z‐score (−0.043 to −0.005; P = .016), and a 20 nmol/mmol creatinine/year increase in urine PYD was associated with a −2.0%/year change in hip dysplasia measured by Reimers migration index (−3.8 to −0.1; P = .037). Conclusions Inflammatory cytokines are high in MPS I. IL‐6 and PYD were associated with progression in joint contracture, short stature, and hip dysplasia over time. Once validated, these biomarkers may prove useful for predicting response to treatment of skeletal disease in MPS I.https://doi.org/10.1002/jmd2.12190biomarkerbonecytokinesHurlerinflammationmucopolysaccharidosis |
| spellingShingle | Troy C. Lund Terence M. Doherty Julie B. Eisengart Rebecca L. Freese Kyle D. Rudser Ellen B. Fung Bradley S. Miller Klane K. White Paul J. Orchard Chester B. Whitley Lynda E. Polgreen Biomarkers for prediction of skeletal disease progression in mucopolysaccharidosis type I JIMD Reports biomarker bone cytokines Hurler inflammation mucopolysaccharidosis |
| title | Biomarkers for prediction of skeletal disease progression in mucopolysaccharidosis type I |
| title_full | Biomarkers for prediction of skeletal disease progression in mucopolysaccharidosis type I |
| title_fullStr | Biomarkers for prediction of skeletal disease progression in mucopolysaccharidosis type I |
| title_full_unstemmed | Biomarkers for prediction of skeletal disease progression in mucopolysaccharidosis type I |
| title_short | Biomarkers for prediction of skeletal disease progression in mucopolysaccharidosis type I |
| title_sort | biomarkers for prediction of skeletal disease progression in mucopolysaccharidosis type i |
| topic | biomarker bone cytokines Hurler inflammation mucopolysaccharidosis |
| url | https://doi.org/10.1002/jmd2.12190 |
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