“…26 We also noted that autoantibodies to other human autoantigens have been reported in normal populations. 49,50 We suspect that the baseline anti-GFAP autoantibody levels we observed in certain healthy controls likely reflect the TBI health history of those subjects-e.g., they may have experienced previous unreported concussions or other subclinical neurological events. 25 It is also presently unclear as to why AutoAb[GFAP] was statistically significantly elevated in those with an acute TBI and history of previous TBI when compared with those with acute TBI without a previous history of TBI, but not healthy controls.…”
We described recently a subacute serum autoantibody response toward glial fibrillary acidic protein (GFAP) and its breakdown products 5-10 days after severe traumatic brain injury (TBI). Here, we expanded our anti-GFAP autoantibody (AutoAb[GFAP]) investigation to the multicenter observational study Transforming Research and Clinical Knowledge in TBI Pilot (TRACK-TBI Pilot) to cover the full spectrum of TBI (Glasgow Coma Scale 3-15) by using acute (<24 h) plasma samples from 196 patients with acute TBI admitted to three Level I trauma centers, and a second cohort of 21 participants with chronic TBI admitted to inpatient TBI rehabilitation. We find that acute patients self-reporting previous TBI with loss of consciousness (LOC) (n = 43) had higher day 1 AutoAb[GFAP] (mean -standard error: 9.11 -1.42; n = 43) than healthy controls (2.90 -0.92; n = 16; p = 0.032) and acute patients reporting no previous TBI (2.97 -0.37; n = 106; p < 0.001), but not acute patients reporting previous TBI without LOC (8.01 -1.80; n = 47; p = 0.906). These data suggest that while exposure to TBI may trigger the AutoAb[GFAP] response, circulating antibodies are elevated specifically in acute TBI patients with a history of TBI. AutoAb[GFAP] levels for participants with chronic TBI (average post-TBI time 176 days or 6.21 months) were also significantly higher (15.08 -2.82; n = 21) than healthy controls ( p < 0.001). These data suggest a persistent upregulation of the autoimmune response to specific brain antigen(s) in the subacute to chronic phase after TBI, as well as after repeated TBI insults. Hence, AutoAb[GFAP] may be a sensitive assay to study the dynamic interactions between postinjury brain and patient-specific autoimmune responses across acute and chronic settings after TBI.
“…26 We also noted that autoantibodies to other human autoantigens have been reported in normal populations. 49,50 We suspect that the baseline anti-GFAP autoantibody levels we observed in certain healthy controls likely reflect the TBI health history of those subjects-e.g., they may have experienced previous unreported concussions or other subclinical neurological events. 25 It is also presently unclear as to why AutoAb[GFAP] was statistically significantly elevated in those with an acute TBI and history of previous TBI when compared with those with acute TBI without a previous history of TBI, but not healthy controls.…”
We described recently a subacute serum autoantibody response toward glial fibrillary acidic protein (GFAP) and its breakdown products 5-10 days after severe traumatic brain injury (TBI). Here, we expanded our anti-GFAP autoantibody (AutoAb[GFAP]) investigation to the multicenter observational study Transforming Research and Clinical Knowledge in TBI Pilot (TRACK-TBI Pilot) to cover the full spectrum of TBI (Glasgow Coma Scale 3-15) by using acute (<24 h) plasma samples from 196 patients with acute TBI admitted to three Level I trauma centers, and a second cohort of 21 participants with chronic TBI admitted to inpatient TBI rehabilitation. We find that acute patients self-reporting previous TBI with loss of consciousness (LOC) (n = 43) had higher day 1 AutoAb[GFAP] (mean -standard error: 9.11 -1.42; n = 43) than healthy controls (2.90 -0.92; n = 16; p = 0.032) and acute patients reporting no previous TBI (2.97 -0.37; n = 106; p < 0.001), but not acute patients reporting previous TBI without LOC (8.01 -1.80; n = 47; p = 0.906). These data suggest that while exposure to TBI may trigger the AutoAb[GFAP] response, circulating antibodies are elevated specifically in acute TBI patients with a history of TBI. AutoAb[GFAP] levels for participants with chronic TBI (average post-TBI time 176 days or 6.21 months) were also significantly higher (15.08 -2.82; n = 21) than healthy controls ( p < 0.001). These data suggest a persistent upregulation of the autoimmune response to specific brain antigen(s) in the subacute to chronic phase after TBI, as well as after repeated TBI insults. Hence, AutoAb[GFAP] may be a sensitive assay to study the dynamic interactions between postinjury brain and patient-specific autoimmune responses across acute and chronic settings after TBI.
“…Recombinant cytokines being used as therapeutics are included in Table III. Watanabe et al 2010 provide a thorough review of examples of cytokine specific autoantibodies as primary causes of disease by neutralizing endogenous cytokine activity, as exacerbating factors of disease by augmenting cytokine signal transduction, as attenuating factors of disease severity, and those that are induced by viral infection or tumor burden (77). For example, presence of anti-IL-1 antibody has been inversely correlated with disease severity in patients with RA (78).…”
“…While multiple lines of evidence support the notion that cytokine specific autoantibodies may be present and ubiquitous in healthy individuals (79), their potential physiological role is less clear. It is hypothesized that they may function by scavenging pro-inflammatory cytokines and inhibiting deleterious Bendocrine^effects, or by serving as carrier proteins, providing a Breservoir^of inactive cytokines (77). These mechanisms should be clearly outlined in a prospective immunogenicity risk assessment with plans for mitigation, i.e., tolerance induction, patient exclusion, real-time monitoring of boosting as deemed needed to preserve patient safety and improve therapeutic efficacy.…”
Abstract. Pre-existing antibodies to biotherapeutic drugs have been detected in drug-naïve subjects for a variety of biotherapeutic modalities. Pre-existing antibodies are immunoglobulins that are either specific or cross-reacting with a protein or glycan epitopes on a biotherapeutic compound. Although the exact cause for pre-existing antibodies is often unknown, environmental exposures to non-human proteins, glycans, and structurally similar products are frequently proposed as factors. Clinical consequences of the pre-existing antibodies vary from an adverse effect on patient safety to no impact at all and remain highly dependent on the biotherapeutic drug modality and therapeutic indication. As such, pre-existing antibodies are viewed as an immunogenicity risk factor requiring a careful evaluation. Herein, the relationships between biotherapeutic modalities to the nature, prevalence, and clinical consequences of pre-existing antibodies are reviewed. Initial evidence for pre-existing antibody is often identified during anti-drug antibody (ADA) assay development. Other interfering factors known to cause false ADA positive signal, including circulating multimeric drug target, rheumatoid factors, and heterophilic antibodies, are discussed.
“…In the field of immune-mediated diseases, the presence of autoantibodies to cytokines has attracted much debate and interest. Theoretically, neutralizing autoantibodies against cytokines may counteract physiological regulation of inflammatory responses, but possibly also serve as a physiological means to down-regulate or balance misdirected or excessive immune responses [3]. Therapeutic use of cytokines, e.g.…”
Section: Introductionmentioning
confidence: 99%
“…A large number of studies have addressed the occurrence and possible roles of autoantibodies to cytokines in different autoimmune conditions, providing evidence of their existence and describing possible associations with clinical outcomes [3]. However, the most frequently used method of detection is different ELISA variants and, as pointed out by Bendtzen et al, there are several points that need to be addressed when developing an anti-cytokine ELISA [8,9]; these precautions apply also for other immunosorbent assays.…”
Beware of antibodies to dietary proteins in "antigen-specific" immunoassays! Falsely positive anti-cytokine antibody tests due to reactivity with bovine serum albumin in rheumatoid arthritis (the Swedish TIRA project)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.