Circulating Autoantibodies Recognize and Bind Dying Neurons Following Injury to the Brain

Abstract

While it is known that autoimmune cells can protect against cell damage following traumatic injury of the brain, the role of autoantibodies in brain injury is less clear. Here we present evidence in adult rats that following a cortical lesion of the brain, circulating IgG autoantibodies bind to dying neurons in the vicinity of the lesion. At intervals that ranged from 4 h to 7 days after making a unilateral lesion of visual cortex, we observed neurons near the lesion that were immunopositive for rat IgG. Many of these IgG-positive neurons were in advanced stages of degeneration. The magnitude of the immunostaining observed was directly proportional to the percent reactivity to rat IgG of the antibodies that were used. Preadsorption of the antibodies with rat serum eliminated the immunostaining. In addition, immunostaining for serum albumin in sections through the cortical lesion was negative, supporting the conclusion that the positive staining for IgG does not result from the passive diffusion of serum proteins into injured cells. Instead, the evidence presented here strongly suggests that naturally occurring IgG autoantibodies bind specifically to dying neurons in the injured brain. We propose that this autoantibody binding may participate in the phagocytosis and removal of injured neurons.

Investigation of antihypothalamus and antipituitary antibodies in amateur boxers: is chronic repetitive head trauma-induced pituitary dysfunction associated with autoimmunity?

“…A possible role of autoimmune process involving the hypothalamic-pituitary region triggered by head trauma has been suggested by studies conducted in animals. In an experimental study, naturally occurring IgG autoantibodies against dying neurons in the injured brain have been detected in adult rats following a cortical lesion, and it has been proposed that autoantibody binding may be involved in the phagocytosis and removal of the injured neurons (13). Furthermore, autoreactive antibodies against neurons and basal lamina have been found in serum following experimental TBI in rats.…”

“…However, none of these mechanisms have been proven, and the mechanism of sports-related head trauma-induced pituitary dysfunction is still unclear. A possible role of autoimmunity has been suggested by studies conducted in animals, which demonstrated naturally occurring IgG autoantibodies against dying neurons in the injured brain of adult rats following a cortical lesion (13) and autoreactive antibodies against neurons and basal lamina in the serum of rats submitted to experimental TBI (14). Supporting these experimental findings, a significant association between antipituitary antibody (APA) positivity and hypopituitarism 3 years after TBI has been clearly demonstrated in a very recent clinical study (15).…”

Antipituitary antibodies after traumatic brain injury: is head trauma-induced pituitary dysfunction associated with autoimmunity?

“…However, the dynamic changes in pituitary function suggest that head trauma may trigger an ongoing process such as autoimmunity (4). A possible role of autoimmunity could be suggested by studies in animals that demonstrated naturally occurring IgG autoantibodies against dying neurons in the injured brain of adult rats following a cortical lesion (7) and autoreactive antibodies against neurons and basal lamina in the serum of rats submitted to experimental TBI (8). Although the antibodies against neurons have been demonstrated in injured animal studies, investigations regarding the occurrence of antipituitary antibodies (APAs) in patients with TBI are lacking in the literature.…”

Utility of Autoantibodies as Biomarkers for Diagnosis and Staging of Neurodegenerative Diseases

“…For example, it has been previously reported that brain-reactive autoantibodies (IgG) are ubiquitous in human sera Oddo, Caccamo, Kitazawa, Tseng, & LaFerla, 2003). This, along with the consistent presence of IgG-positive neurons in regions of AD pathology, suggests that chronic BBB compromise allows autoantibodies to gain access to their targets on the surfaces of neurons (Levin et al, 2010;Stein, Fedynyshyn, & Kalil, 2002). Soluble Aβ42 is known to preferentially accumulate on the surfaces of certain types of neurons, especially those that abundantly express the α-7 nAChR, for which Aβ42 has strong binding affinity (Nagele et al, 2002;Wang et al, 2000).…”