Human anti-animal antibodies

Kricka LJ. Human anti-animal antibody interferences in immunological assays. Clin Chem 1999 45 942-56. 

Current immunoassays make use of polyclonal or monoclonal antibodies to capture test analytes from serum or plasma samples. A limitation for all sandwich-type immunoassays occurs when the patient sample contains heterophile or human anti-animal antibodies. These antibodies occur in patients with autoimmune diseases and exposure to animal antigens, respectively. When present, these antibodies bind to both the capture and signal antitroponin antibodies, thereby producing a falsely positive signal in the absence of the analyte (Figure 92.2b). Commercial assays for cardiac troponin are not immune... 

In chimpanzees, administration of Fab fragments of a monoclonal anti-F-VII antibody preceding an endotoxin bolus injection effectively blocked the activation of the coagulation pathway (B25). Administration of monoclonal anti-lL-6 under the same experimental conditions attenuated the activation of coagulation, while the fibrinolytic system remained unaltered. However, administration of monoclonal anti-TNF enhanced the tendency to microvascular thrombosis (P17,18). Monoclonal anti-TF antibodies administered to baboons as a pretreatment attenuated coagulopathy after induction of E. coli sepsis in these animals (T4). Primates pretreated with anti-C5a antibodies before infusion of E. coli developed less hypotension and had better survival rates than untreated animals, who developed ARDS and septic shock with a mortality rate of 75% (S35, Z6). No favorable treatment results have been published yet with one of these treatment modalities given to humans. 

Thus, the tetravalency, anti-inflammatory properties and molecular stability of slgA make it particularly suitable for protective passive immunity when applied to mucosal surfaces. To date, the clinical evaluation of slgA protection in humans and animal models has been very limited. Indeed most studies have employed monomeric IgA monoclonal antibodies [3,15]. Hence, differences in IgA and IgG protective activities at the mucosal level have often not been observed [15]. Only a few studies have demonstrated the superior activity of polymeric IgA or slgA compared with monomeric IgG or IgA [16]. In order to determine the efficacy of slgA, future animal experiments and clinical trials are needed to compare the activities of IgG monoclonal antibodies and their slgA counterparts. The ability to engineer slgAs in plants will allow these comparisons to be made [17]. 

CD8+CD69+ T cells was not observed in vivo. NK cells appeared to increase during the recovery period and an expansion of B cells was observed that persisted longer than that observed for T cells in individual animals. Transient, moderate elevations of serum IL-2, IL-5 (anti-inflammatory TH2-type cytokine), and IL-6 (inflammatory cytokine) was observed in individual animals at 2 or 24 hours following the initial dose but were not observed on Days 17 or 62 no changes in TNFa or IFNy (major pro-inflammatory cytokines) were observed. Thus, TGN1412 did not appear to be associated with a cytokine-release syndrome that has been observed in humans with upon administration of agonistic anti-CD3 antibodies.78... 

A soluble receptor has been identified in vivo which, when produced by recombinant means and administered at higher levels, does act as an effective receptor antagonist. Fab fragments of a humanized anti-IL-5 monoclonal antibody (Chapter 10) have also been produced, which can reduce IL-5-mediated effects in animal models. 

Other problems that may be encountered are related to the immunologic effects of insulin use. Certain forms of insulin may evoke an immune reaction and stimulate antibody production. These anti-insulin antibodies may cause an allergic reaction in some individuals, as well as a resistance to the exogenous insulin molecule. As discussed previously, the incidence of these immunologic reactions seems to be greater when animal (i.e., pork) forms of insulin are used. Consequently, these problems are often resolved by switching the patient to another type of preparation, preferably biosynthetic human insulin. 

Between October 30 and November 4, 2000, 11 persons were intoxicated due to ingestion of a serranid fish Epinephelus sp. in Kochi Prefecture, Japan. Their symptoms included severe muscle pain, low back pain, and discharge of black urine. The causative agent was identified as palytoxin on the basis of delayed haemolytic activity, which was inhibited by an anti-palytoxin antibody and ouabain (Taniyama et al. 2002). Although the toxic dose of palytoxin in humans could not be determined, extrapolation of the data available in animals will give a toxic dose in a human of about 4 pg. This fact places palytoxin among the most toxic nonproteinic animal toxins known to date (Taniyama et al. 2002) however, its mechanisms of toxicity remain to be elucidated. 

As discussed earlier, high-affinity anti-drug antibodies produce effects on the pharmacokinetics and pharmacodynamics of drugs in animals and humans. For new therapeutic applications, these effects need to be fully tested in animals before administration to humans. In addition, from a basic science viewpoint, it will be necessary to develop relevant pharmacokinetic and pharmacodynamic models of... 

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