Characterization of the Antibody Response after Cervical Spinal Cord Injury

Ulndreaj, Antigona; Τζέκου, Αποστολία; Mothe, Andrea J.; Siddiqui, Ahad M.; Dragas, Rachel; Tator, Charles H.; Torlakovic, Emina; Fehlings, Michael G.

doi:10.1089/neu.2016.4498

Cited by 28 publications

(40 citation statements)

References 69 publications

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“…Serum IgG levels in SCI patients are significantly higher at 1 month after injury compared to healthy subjects, while IgM levels fail to reach statistical significance (Figures 1A,B ). In experimental models, at the acute phase, total IgG and IgM serum levels increase after low thoracic lesions ( 3 ) and decrease after cervical lesions ( 16 ). Contrasting with these observations, in our study neither neurological level of injury nor severity affects total IgG or IgM serum levels (Figures 1C – F ).…”

Section: Resultsmentioning

confidence: 99%

“…Accordingly, it has been reported that high thoracic lesions, but not low thoracic, inhibit the production of antibodies after immunization with exogenous antigens in mice ( 8 , 15 ). However, cervical injuries increase AAb levels against spinal cord self-antigens ( 16 ). These opposed results between the responses of antibodies against exogenous and self-antigens may be explained by the observations in rodent experimental models showing that (i) SCI only impairs the generation of new antibody responses but preserves already existing immunity ( 17 ) and that (ii) AAbs detected after SCI may exist before lesion ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

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Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies

et al. 2018

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Spinal cord injury (SCI) results in long-term neurological and systemic consequences, including antibody-mediated autoimmunity, which has been related to impaired functional recovery. Here we show that autoantibodies that increase at the subacute phase of human SCI, 1 month after lesion, are already present in healthy subjects and directed against non-native proteins rarely present in the normal spinal cord. The increase of these autoantibodies is a fast phenomenon–their levels are already elevated before 5 days after lesion–characteristic of secondary immune responses, further supporting their origin as natural antibodies. By proteomics studies we have identified that the increased autoantibodies are directed against 16 different nervous system and systemic self-antigens related to changes known to occur after SCI, including alterations in neural cell cytoskeleton, metabolism and bone remodeling. Overall, in the context of previous studies, our results offer an explanation to why autoimmunity develops after SCI and identify novel targets involved in SCI pathology that warrant further investigation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies

et al. 2018

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“…We have previously shown that cervical SCI results in disturbed peripheral adaptive immune responses in the spleen of rats [ 15 ] and blood of humans [ 16 ]. Others have shown dysregulation of peripheral adaptive immunity in the spleen [ 10 ], blood [ 17 ] and lymph nodes (LNs) [ 9 ] in experimental and clinical thoracic SCIs.…”

Section: Introductionmentioning

confidence: 99%

Effects of experimental cervical spinal cord injury on peripheral adaptive immunity

et al. 2020

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Adaptive immunity is critical for controlling infections, which are a leading cause of morbidity and mortality in patients with spinal cord injury (SCI). In rats and mice, compromised peripheral adaptive immune responses, as shown by splenic atrophy and lowered frequencies of peripheral lymphocytes, were shown to result from high-level thoracic SCI. However, whether cervical SCI, which is the most common level of SCI in humans, impairs adaptive immunity remains largely unknown. In the present study, we induced cervical SCI in rats at the C7/T1 level by clip compression and looked at changes in peripheral adaptive immunity at 2-, 10- and 20-weeks post-injury. Specifically, we quantified changes in the frequencies of T- and B- lymphocytes in the blood and the mandibular and deep cervical lymph nodes, which drain the cervical spinal cord. We also assessed changes in serum IgG and IgM immunoglobulin levels, as well as spleen size. We found a significant decline in circulating T- and B- cell frequencies at 10 weeks post-SCI, which returned to normal at 20 weeks after injury. We found no effect of cervical SCI on T- and B- cell frequencies in the draining lymph nodes. Moreover, cervical SCI had no effect on net spleen size, although injured rats had a higher spleen/body weight ratio than sham controls at all time points of the study. Lastly, IgG and IgM immunoglobulin declined at 2 weeks, followed by a significant increase in IgM levels at 10 weeks of injury. These data indicate that cervical SCI causes a significant imbalance in circulating lymphocytes and immunoglobulin levels at 2 and 10 weeks. As we discuss in this article, these findings are largely in line with clinical observations, and we anticipate that this study will fuel more research on the effect of adaptive immunity on SCI recovery.

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“…Briefly, the spleen plays an important role in erythrocyte turnover, adaptive immunity, antibody production, and, more recently revealed, the mobilization of monocytes/macrophages (Mφ) following tissue injury [ 4 ]. In the context of high-level SCI, several studies have evaluated dysfunctional antibody synthesis following loss of splenic sympathetic preganglionic innervation [ 5 – 7 ] and the production of autoantibodies against spinal cord tissue [ 8 ]. Yet, equally important is the acute response to trauma-induced inflammation, where the spleen initiates production of tumor necrotic factor-α (TNFα), mostly by resident Mφs, and in turn influences the recruitment of immune cells to the inflamed tissue [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Splenic involvement in umbilical cord matrix-derived mesenchymal stromal cell-mediated effects following traumatic spinal cord injury

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Hacker

Hong

et al. 2018

J Neuroinflammation

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BackgroundThe spleen plays an important role in erythrocyte turnover, adaptive immunity, antibody production, and the mobilization of monocytes/macrophages (Mφ) following tissue injury. In response to trauma, the spleen initiates production of inflammatory cytokines, which in turn recruit immune cells to the inflamed tissue, exacerbating damage. Our previous work has shown that intravenous mesenchymal stromal cell (MSC) infusion has potent immunomodulatory effects following spinal cord injury (SCI), associated with the transplanted cells homing to and persisting within the spleen. Therefore, this work aimed to characterize the relationship between the splenic inflammatory response and SCI pathophysiology, emphasizing splenic involvement in MSC-mediated effects.MethodsUsing a rodent model of cervical clip-compression SCI, secondary tissue damage and functional recovery were compared between splenectomised rodents and those with a sham procedure. Subsequently, 2.5 million MSCs from the term human umbilical cord matrix cells (HUCMCs) were infused via tail vein at 1-h post-SCI and the effects were assessed in the presence or absence of a spleen.ResultsSplenectomy alone had no effect on lesion volume, hemorrhage, or inflammation. There was also no significant difference between the groups in functional recovery and those in lesion morphometry. Yet, while the infusion of HUCMCs reduced spinal cord hemorrhage and increased systemic levels of IL-10 in the presence of a spleen, these effects were lost with splenectomy. Further, HUCMC infusion was shown to alter the expression levels of splenic cytokines, suggesting that the spleen is an important target and site of MSC effects.ConclusionsOur results provide a link between MSC function and splenic inflammation, a finding that can help tailor the cells/transplantation approach to enhance therapeutic efficacy.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1243-0) contains supplementary material, which is available to authorized users.

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Characterization of the Antibody Response after Cervical Spinal Cord Injury

Cited by 28 publications

References 69 publications

Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies

Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies

Effects of experimental cervical spinal cord injury on peripheral adaptive immunity

Splenic involvement in umbilical cord matrix-derived mesenchymal stromal cell-mediated effects following traumatic spinal cord injury

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