Abstract
PurposeThe 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).MethodsDisc 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.ResultsHigher 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.ConclusionTCC 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.
Highlights
Disc degeneration (DD) and associated inflammation often lead to low back pain, one of the major causes of disability worldwide, representing a very large economic burden [1]
We have addressed the following research questions: 1. Is terminal complement complex (TCC) deposition higher in tissue samples from patients with various disc pathologies compared to age-matched controls?
No correlation was found between age, Pfirrmann grade or Modic changes and different disc degeneration (DD) diagnoses: disc herniation (DH), spondylolisthesis (SL), osteochondrosis (OC) and others including compressive fracture, fall back surgery syndrome, degenerative scoliosis, chronic low back pain and stenosis (Supplementary Fig. S1)
Summary
Disc degeneration (DD) and associated inflammation often lead to low back pain, one of the major causes of disability worldwide, representing a very large economic burden [1]. Current treatments (physiotherapy, disc replacement, among others) decrease symptoms progression, but fail to restore the native intervertebral disc (IVD) properties. Extended author information available on the last page of the article. Characteristic features of degenerated IVDs are structural changes, such as reduced disc height, a transformation of the central gelatinous nucleus pulposus (NP) into a more fibrotic tissue, with reduced water binding capacity due to progressing degradation and less proteoglycan production. The annulus fibrosus (AF) suffers increased breakdown of the structural matrix components which contribute to fissures and tears [3, 4]
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