High avidity cytokine autoantibodies in health and disease: Pathogenesis and mechanisms

Plasma Anti-Glial Fibrillary Acidic Protein Autoantibody Levels during the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study

“…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.…”

Pre-existing Antibody: Biotherapeutic Modality-Based Review

“…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.…”

Beware of Antibodies to Dietary Proteins in “Antigen-specific” Immunoassays! Falsely Positive Anticytokine Antibody Tests Due to Reactivity with Bovine Serum Albumin in Rheumatoid Arthritis (The Swedish TIRA Project)

“…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.…”

“…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.…”