Abstract
Therapeutic immunoglobulins are used in the treatment of immunodeficiencies as well as several autoimmune and inflammatory diseases. These intravenous immunoglobulins (IVIg) represent the healthy human IgG repertoire, which can be reactive for both self and non-self antigens. A better characterization of IVIg’s repertoire is an important aspect to enable its effective utilization as an immunomodulatory treatment. In this study we have investigated the reactivity of IgG1, IgG2, IgG3 and IgG4 present in IVIg for a small selection of antigens, including actin, DNA, ferritin and thyroglobulin. We observed that two commercial preparations of therapeutic immunoglobulins contain very high reactivity for thyroglobulin, which was predominantly detected by IgG4. Since IgG4 antibodies can have immunomodulatory properties, these result suggest that these anti-thyroglobulin may have a role in the IVIg treatment of autoimmune disease characterized by high avidity for anti-thyroglobulin antibodies such as Hashimoto’s disease.
Highlights
Therapeutic immunoglobulins, namely intravenous immunoglobulins (IVIg), are currently used in the treatment of immunodeficiencies as well as several autoimmune and inflammatory diseases
Both IVIg preparations were tested simultaneously and showed similar capacity to bind dsDNA, actin, ferritin, thyroglobulin and transferrin. In this ELISA system, the total IgG anti-species cross-reactivity of IVIg for murine IgG molecules was comparable to that of transferrin, thyroglobulin and ferritin antigens Analysis done with both IVIg adjusted to 250 μg/mL resulted in O.D. varying from 1.0 to more than 3.5 in most cases indicating that these reactivity
In this study we showed that IVIg content of autoreactive antibodies varied according to their isotypes
Summary
Therapeutic immunoglobulins, namely intravenous immunoglobulins (IVIg), are currently used in the treatment of immunodeficiencies as well as several autoimmune and inflammatory diseases (reviewed in [1]). IVIg is constituted of the human healthy IgG repertoire (>98% IgG), which contains antibodies against pathogens as well as. Anti-inflammatory properties of IVIg are related to their capacities to down-modulate activation of immune cells or to reduce the negative impact of pathologic IgG [1] [3]. It is well known that all IgG subclasses are not equal in their potential to modulate immune functions such as complement activation or Fcgamma receptor stimulation [4]. IgG4 antibodies do not activate complement but have anti-inflammatory activities [6]-[9]. Following an in vivo Fab-arm exchange mechanism, the IgG4 molecule can become bispecific, a property that can be associated to anti-inflammatory functions [8] as well as to rheumatoid arthritis [10]. Several diseases are associated to very high levels of IgG4 in blood and organs leading to the recent definition of hyper-IgG4 syndrome as an emerging systemic disease [11]-[14]
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