Autoreactivity against myelin basic protein in patients with chronic paraplegia

Abstract

Introduction Previous studies have shown the existence of either cellular or humoral MBP-reactive elements up to 5 years after spinal cord injury (SCI), but not the presence of both after 10 years. Materials and methods Twelve SCI patients, with more than 10 years of evolution, and 18 healthy blood donors were studied. Lymphocyte proliferation (colorimetricBrdU ELISA assay) and antibody titers against MBP (ELISA Human IgG MBP-specific assay) were assessed. Results SCI patients presented a significant T-cell proliferation against MBP (lymphocyte proliferation index: 3.7 ± 1.5, mean ± SD) compared to control individuals (0.7 ± 0.3; P \ 0.001). Humoral response analysis yielded a significant difference (P \ 0.0001) between the antibody titers of controls and SCI patients. A significant correlation between cellular and humoral responses was observed. Finally, patients with an ASIA B presented the highest immune responses. Conclusion This work demonstrates, for the first time, the existence of both cellular and humoral responses against MBP in the chronic stages ([10 years) of injury.

The paradox of chronic neuroinflammation, systemic immune suppression, autoimmunity after traumatic chronic spinal cord injury

“…Whether these are functionally effective inflammatory or anti-inflammatory reactions is questionable, especially since there is no evidence that either is resolved in affected individuals or animal models. Indeed, intraspinal inflammation persists indefinitely (Prüss et al, 2011; Popovich et al, 1997; Rosenberg et al, 2005) and depending on injury level, anti-inflammatory or even autoimmune pathologies develop (Popovich et al, 1997; Hayes et al, 2002; Ankeny 2006; Zajarias-Fainsod et al, 2012). Interactions between the central nervous and immune systems, i.e., the two main systems regulating homeostasis throughout the body, are not limited to aberrant immune cell activation/accumulation behind the blood-spinal cord barrier (BSB).…”

B-Cell Maturation Antigen, A Proliferation-Inducing Ligand, and B-Cell Activating Factor Are Candidate Mediators of Spinal Cord Injury-Induced Autoimmunity

“…28 More recently, increased myelin basic protein antibody titers were found in 12 subjects with SCI ( < 10 years) compared with 18 healthy controls. 29 The subjects with SCI also demonstrated increased T-cell proliferation against myelin basic protein. The authors speculate that this cellular and humoral response may not necessarily be pathological, because all subjects with SCI demonstrated stable neurological impairment over the course of the observation period despite the presence of autoantibodies.…”

“…Despite these limitations, we offer evidence that after SCI, peripheral blood mononuclear cells overexpress BCMA, BAFF, and APRIL. Based on previous studies, 7,22,29 we speculate that this promotes SCI-induced autoimmunity by allowing B cells to become activated by CNS debris and escape clonal deletion. These activated B cells secrete autoantibodies that contribute to tissue damage and neurotoxicity after SCI.…”

Spinal Cord Injury

“…Antibodies to CNS proteins are present in the serum of SCI individuals chronically (Zajarías-Fainsod et al, 2012); this parallels the activation and maintenance of B cells observed in rodent models of SCI (Ankeny et al, 2006Donnelly and Popovich, 2008). Antibodies to CNS proteins are present in the serum of SCI individuals chronically (Zajarías-Fainsod et al, 2012); this parallels the activation and maintenance of B cells observed in rodent models of SCI (Ankeny et al, 2006Donnelly and Popovich, 2008).…”