Abstract
Introduction:
Traumatic spinal cord injury (TSCI) inflicts neurological function from the lesion site and caudally. TSCI ablates neuro-immunological interaction and immunological dysfunction develops resulting in chronic neuroinflammation and autoimmunity. The initial acute inflammation appropriatly clear cell debris and promote axonal growth, but a mosaicism of concommitant effects deteriorates the path. Inflammation increases the intraspinal pressure and thus decreases the intraspinal perfusion pressure with possible secondary ischaemic injury. The caudally lost vascular control and therefrom hypotensive state may amplify this effect. Myeloid cells’ phagocytosis of myelin initiates the formation and decay of foamy cells that triggers proinflammatory cytokines. Increasing magnitude and level of TSCI increases the intensity of both spinal cord injury-immuno depression syndrome, and autonomic dysreflexia. Both beeing systemically immunodepressive, thus protective against autoimmunity, but inevitably increases infectious susceptibility and thus the risk of being hospitalized for infections. A known risk factor of developing every autoimmune disease. Collectively these factors may attribute to the deteoriating inflammatory cascade establishing chronic neuroinflammation and possible autoimmunity.
Experimental murine and observational human studies describe manifest autoantibodies post-TSCI, heramongst anti-myelin basic protein, anti-double stranded DNA antibodies, and anti-nuclear antibodies. Manifest autoimmunity develops post-TSCI, especially against CNS antigens, but there is an unelucidated distinction between autoimmunity - sensitization to self - and symptomatic autoimmune disease (AD).
Objectives:
To evaluate if TSCI patients have an increased incidense rate ratio (IRR) of developing AD.
Methods:
Based on a range of public Danish national registries, a nationwide studypopulation was collected from 1945-2018. The studyperiod was 1980-2018 and 1977-1979 was washoutperiod of prevalent cases with TSCI and AD. Specifically for Diabetes mellitus type 1 the studyperiod was 1988-2018 and 1987 was washout. A survival analysis was performed using Poissons Log-linear regression with person-years at risk as offset variable. The IRR was estimated for developing eight groups of ADs given a TSCI. Usual epidemiological confounders and, for ADs specifically, hospitalization for an infection was adjusted to evaluate the effect size of the modelled causal path.
Results:
N= 4,878,388 individuals and 138,161,130 person-years (PY) at risk was included. Hereof 3,273 was diagnosed with TSCI constituting 50,918 PY at risk. A TSCI population had an overall IRR of 1·32 (95% CI 1·16; 1·50) of getting any autoimmune diagnosis. For Other neurologic (constituting Myasthenia Gravis and Idiopathic polyneuropathy) 3·71 (95% CI 1·99; 6·91) and Multiple Sclerosis 3·23 (95% CI 2·21; 4·71) we found the strongest association. A significantly positive association between TSCI and Dermatologic and Systemic ADs was described, respectively 1·90 (95% CI 1·37; 2·62) and 1·50 (95% CI 1·13; 2·00). The remaining outcome groups; Endocrine & haematologic, Gastroenterologic, DM-1 and Iridocyclitis showed no association with TSCI. By constructing models with and without adjustment for hospitalization for infection we showed that this has an effect on the association and probably is an important mediator of the association.
Conclusions:
TSCI is an individual risk factor of developing certain ADs, especially those of neurologic origin. Furthermore, hospitalization for infections is an important modifiable risk factor.
Traumatic spinal cord injury (TSCI) inflicts neurological function from the lesion site and caudally. TSCI ablates neuro-immunological interaction and immunological dysfunction develops resulting in chronic neuroinflammation and autoimmunity. The initial acute inflammation appropriatly clear cell debris and promote axonal growth, but a mosaicism of concommitant effects deteriorates the path. Inflammation increases the intraspinal pressure and thus decreases the intraspinal perfusion pressure with possible secondary ischaemic injury. The caudally lost vascular control and therefrom hypotensive state may amplify this effect. Myeloid cells’ phagocytosis of myelin initiates the formation and decay of foamy cells that triggers proinflammatory cytokines. Increasing magnitude and level of TSCI increases the intensity of both spinal cord injury-immuno depression syndrome, and autonomic dysreflexia. Both beeing systemically immunodepressive, thus protective against autoimmunity, but inevitably increases infectious susceptibility and thus the risk of being hospitalized for infections. A known risk factor of developing every autoimmune disease. Collectively these factors may attribute to the deteoriating inflammatory cascade establishing chronic neuroinflammation and possible autoimmunity.
Experimental murine and observational human studies describe manifest autoantibodies post-TSCI, heramongst anti-myelin basic protein, anti-double stranded DNA antibodies, and anti-nuclear antibodies. Manifest autoimmunity develops post-TSCI, especially against CNS antigens, but there is an unelucidated distinction between autoimmunity - sensitization to self - and symptomatic autoimmune disease (AD).
Objectives:
To evaluate if TSCI patients have an increased incidense rate ratio (IRR) of developing AD.
Methods:
Based on a range of public Danish national registries, a nationwide studypopulation was collected from 1945-2018. The studyperiod was 1980-2018 and 1977-1979 was washoutperiod of prevalent cases with TSCI and AD. Specifically for Diabetes mellitus type 1 the studyperiod was 1988-2018 and 1987 was washout. A survival analysis was performed using Poissons Log-linear regression with person-years at risk as offset variable. The IRR was estimated for developing eight groups of ADs given a TSCI. Usual epidemiological confounders and, for ADs specifically, hospitalization for an infection was adjusted to evaluate the effect size of the modelled causal path.
Results:
N= 4,878,388 individuals and 138,161,130 person-years (PY) at risk was included. Hereof 3,273 was diagnosed with TSCI constituting 50,918 PY at risk. A TSCI population had an overall IRR of 1·32 (95% CI 1·16; 1·50) of getting any autoimmune diagnosis. For Other neurologic (constituting Myasthenia Gravis and Idiopathic polyneuropathy) 3·71 (95% CI 1·99; 6·91) and Multiple Sclerosis 3·23 (95% CI 2·21; 4·71) we found the strongest association. A significantly positive association between TSCI and Dermatologic and Systemic ADs was described, respectively 1·90 (95% CI 1·37; 2·62) and 1·50 (95% CI 1·13; 2·00). The remaining outcome groups; Endocrine & haematologic, Gastroenterologic, DM-1 and Iridocyclitis showed no association with TSCI. By constructing models with and without adjustment for hospitalization for infection we showed that this has an effect on the association and probably is an important mediator of the association.
Conclusions:
TSCI is an individual risk factor of developing certain ADs, especially those of neurologic origin. Furthermore, hospitalization for infections is an important modifiable risk factor.
| Original language | English |
|---|---|
| Publication date | 8 Oct 2023 |
| Publication status | Published - 8 Oct 2023 |
| Event | ISCoS 62nd annual scientific meeting - Edinburgh International Conference Centre, Scotland, Edinburgh, United Kingdom Duration: 8 Oct 2023 → 11 Oct 2023 Conference number: 62 http://www.iscosmeetings2023.org |
Conference
| Conference | ISCoS 62nd annual scientific meeting |
|---|---|
| Number | 62 |
| Location | Edinburgh International Conference Centre, Scotland |
| Country/Territory | United Kingdom |
| City | Edinburgh |
| Period | 08/10/2023 → 11/10/2023 |
| Internet address |