A NATIONWIDE COHORT STUDY OF AUTOIMMUNE/-INFLAMMATORY DISEASE EVOLVED POSTTRAUMATIC TO SPINAL CORD INJURY

TY - CONF

T1 - A NATIONWIDE COHORT STUDY OF AUTOIMMUNE/-INFLAMMATORY DISEASE EVOLVED POSTTRAUMATIC TO SPINAL CORD INJURY

AU - Nielsen, Tim Damgaard

AU - Bech, Bodil Hammer

AU - Laursen, Thomas Munk

AU - Rasmussen, Mikkel Mylius

PY - 2023/10/4

Y1 - 2023/10/4

N2 - Introduction: Traumatic spinal cord injury (TSCI) inflicts neurological function from the lesion site and caudally. TSCI ablates neuro-immunological interaction and immunological dysfunction develops from a mosaic of parallel factors. Systemic infectious susceptibility increases from spinal cord injury-immuno depression syndrom and autonomic dysreflexia, which emperically inflicts neurologic rehabilitation and increases the risk of autoimmune diseases. Those factors collectively may lead to secondary injury, persisting inflammation, and autoimmunity.Experimental murine and observational human studies describe manifest autoantibodies post-TSCI, amongst 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. 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.

AB - Introduction: Traumatic spinal cord injury (TSCI) inflicts neurological function from the lesion site and caudally. TSCI ablates neuro-immunological interaction and immunological dysfunction develops from a mosaic of parallel factors. Systemic infectious susceptibility increases from spinal cord injury-immuno depression syndrom and autonomic dysreflexia, which emperically inflicts neurologic rehabilitation and increases the risk of autoimmune diseases. Those factors collectively may lead to secondary injury, persisting inflammation, and autoimmunity.Experimental murine and observational human studies describe manifest autoantibodies post-TSCI, amongst 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. 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.

UR - https://www.eurospine.org/events/annual-meeting/2023/

M3 - Poster

T2 - Eurospine 2023

Y2 - 4 October 2023 through 6 October 2023

ER -