Graciosa Q Teixeira1, Zhiyao Yong1, Raquel M Goncalves1,2,3,4, Amelie Kuhn5, Jana Riegger5, Helena Brisby6,7, Helena Barreto Henriksson6,7,8, Michael Ruf9, Andreas Nerlich10, Uwe M Mauer11, Anita Ignatius1, Rolf E Brenner5, Cornelia Neidlinger-Wilke12. 1. Institute of Orthopaedic Research and Biomechanics, Trauma Research Centre, Ulm University, Ulm, Germany. 2. Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal. 3. Instituto de Engenharia Biomédica (INEB), Universidade do Porto, Porto, Portugal. 4. Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal. 5. Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, Ulm University, Ulm, Germany. 6. Department of Orthopedics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 7. Department of Orthopedics, Sahlgrenska University Hospital, Gothenburg, Sweden. 8. Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. 9. Center for Spine Surgery, Orthopedics, and Traumatology, SRH-Klinikum Karlsbad-Langensteinbach, Karlsbad, Germany. 10. Department of Pathology, Academic Hospital Munich-Bogenhausen, Munich, Germany. 11. Department of Neurosurgery, German Armed Forces Hospital, Ulm, Germany. 12. Institute of Orthopaedic Research and Biomechanics, Trauma Research Centre, Ulm University, Ulm, Germany. cornelia.neidlinger-wilke@uni-ulm.de.
Abstract
PURPOSE: The complement system is a crucial part of innate immunity. Recent work demonstrated an unexpected contribution to tissue homeostasis and degeneration. This study investigated for the first time, in human disc tissues, the deposition profile of the complement activation product terminal complement complex (TCC), an inflammatory trigger and inducer of cell lysis, and its inhibitor CD59, and their correlation with the degree of disc degeneration (DD). METHODS: Disc biopsies were collected from patients diagnosed with DD (n = 39, age 63 ± 12) and adolescent idiopathic scoliosis (AIS, n = 10, age 17 ± 4) and compared with discs from healthy Young (n = 11, age 7 ± 7) and Elder (n = 10, age 65 ± 15) donors. Immunohistochemical detection of TCC and CD59 in nucleus pulposus (NP), annulus fibrosus (AF) and endplate (EP) was correlated with age, Pfirrmann grade and Modic changes. RESULTS: Higher percentage of TCC+ cells was detected in the NP and EP of DD compared to Elder (P < 0.05), and in the EP of Young versus Elder (P < 0.001). In DD, TCC deposition was positively correlated with Pfirrmann grade, but not with Modic changes, whereas for Young donors, a negative correlation was found with age, indicating TCC's involvement not only in DD, but also in early stages of skeletal development. Higher CD59 positivity was found in AIS and DD groups compared to Young (P < 0.05), and it was negatively correlated with the age of the patients. CONCLUSION: TCC deposition positively correlated with the degree of disc degeneration. A functional relevance of TCC may exist in DD, representing a potential target for new therapeutics.
PURPOSE: The complement system is a crucial part of innate immunity. Recent work demonstrated an unexpected contribution to tissue homeostasis and degeneration. This study investigated for the first time, in human disc tissues, the deposition profile of the complement activation product terminal complement complex (TCC), an inflammatory trigger and inducer of cell lysis, and its inhibitor CD59, and their correlation with the degree of disc degeneration (DD). METHODS: Disc biopsies were collected from patients diagnosed with DD (n = 39, age 63 ± 12) and adolescent idiopathic scoliosis (AIS, n = 10, age 17 ± 4) and compared with discs from healthy Young (n = 11, age 7 ± 7) and Elder (n = 10, age 65 ± 15) donors. Immunohistochemical detection of TCC and CD59 in nucleus pulposus (NP), annulus fibrosus (AF) and endplate (EP) was correlated with age, Pfirrmann grade and Modic changes. RESULTS: Higher percentage of TCC+ cells was detected in the NP and EP of DD compared to Elder (P < 0.05), and in the EP of Young versus Elder (P < 0.001). In DD, TCC deposition was positively correlated with Pfirrmann grade, but not with Modic changes, whereas for Young donors, a negative correlation was found with age, indicating TCC's involvement not only in DD, but also in early stages of skeletal development. Higher CD59 positivity was found in AIS and DD groups compared to Young (P < 0.05), and it was negatively correlated with the age of the patients. CONCLUSION: TCC deposition positively correlated with the degree of disc degeneration. A functional relevance of TCC may exist in DD, representing a potential target for new therapeutics.
Entities:
Keywords:
Back pain; Complement system; Inflammation; Innate immunity; Scoliosis
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