Immunoglobulins—Basic considerations

Mix, Eilhard; Goertsches, Robert; Zett, Uwe K.

doi:10.1007/s00415-006-5002-2

Cited by 60 publications

(37 citation statements)

References 12 publications

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“…The human humoral system is constituted by five major classes of antibodies, but human placenta seems to be impermeable to all classes except IgG (Avrech et al, 1994;Mix et al, 2006). IgG in itself is a class of antibodies consisting of four subclasses: IgG1, IgG2, IgG3, and IgG4.…”

Section: Maternofetal Transfer Of Antibodies In Humans Igg Antibody (mentioning

confidence: 99%

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An interspecies comparison of placental antibody transfer: New insights into developmental toxicity testing of monoclonal antibodies

Pentšuk

Laan

2009

Birth Defects Research Pt B

251

153

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There are profound differences in maternofetal transfer of immunoglobulins between species with extensive gestational transfer of maternal immunoglobulins in primates (including humans) via the chorioallantoic placenta as well as in rabbits and guinea pigs via the inverted yolk sac splanchnopleure. In contrast, other neonatal rodents (rats and mice) receive passive immunity predominantly postnatally. This transfer is mediated principally via FcRn receptors. Therapeutic monoclonal antibodies (mAbs) are most commonly of the IgG1 subclass, which is transported most efficiently to the fetus. In all animal species used for testing developmental toxicity, fetal exposure to IgG is very low during organogenesis, but this increases during the latter half of gestation such that the neonate is born with an IgG1 concentration similar to the mother (but not rats and mice). Review of mAb developmental toxicity studies of licensed products reveals Cynomolgus monkey as the species used in the majority of the cases (10 out of 15). Pregnancy outcome data from women gestationally exposed to mAb is limited. In general, the findings are consistent with the expected low exposure during organogenesis. Guinea-pigs and rabbits are potential candidates as "alternatives" to the use of nonhuman primates as the maternofetal transfer in the last part of gestation is at a level similar in humans. Based on the pattern of placental transfer of IgG in humans, study designs that allow detection of both the indirect effects in early gestation plus the effects of direct fetal exposure in mid and late gestation are recommended for developmental toxicity of mAbs.

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Section: Maternofetal Transfer Of Antibodies In Humans Igg Antibody (mentioning

confidence: 99%

“…Recombinant antibody medicines are used in oncology, in body imaging diagnostics, for treatment of autoimmune diseases, for passive immunization in infections, to neutralize intoxications, and to prevent graft rejection in transplantation, among other uses (Mix et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

An interspecies comparison of placental antibody transfer: New insights into developmental toxicity testing of monoclonal antibodies

Pentšuk

Laan

2009

Birth Defects Research Pt B

251

153

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“…Antibody has a fundamental role in the adaptive immune response against foreign antigens (1) by forming immune complexes that neutralize and mediate the clearance of pathogen-derived toxins/substances, (2) by opsonizing pathogens to prevent further infection and facilitate their removal by professional phagocytes and (3) by activating the classical complement pathway. 50 In the event of autoimmunity, autoantibodies can also be induced against endogenous molecules, such as IgG, in patients with rheumatoid arthritis 51 and nuclear components in SLE patients. 52 Interestingly, serum IgM antibodies have been shown to have an important role in apoptotic cell removal in vitro and in vivo by facilitating C1q binding and the activation of the classical complement pathway on apoptotic cells.…”

Section: Opsoninmentioning

confidence: 99%

Molecular mechanisms of late apoptotic/necrotic cell clearance

2009

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Phagocytosis serves as one of the key processes involved in development, maintenance of tissue homeostasis, as well as in eliminating pathogens from an organism. Under normal physiological conditions, dying cells (e.g., apoptotic and necrotic cells) and pathogens (e.g., bacteria and fungi) are rapidly detected and removed by professional phagocytes such as macrophages and dendritic cells (DCs). In most cases, specific receptors and opsonins are used by phagocytes to recognize and bind their target cells, which can trigger the intracellular signalling events required for phagocytosis. Depending on the type of target cell, phagocytes may also release both immunomodulatory molecules and growth factors to orchestrate a subsequent immune response and wound healing process. In recent years, evidence is growing that opsonins and receptors involved in the removal of pathogens can also aid the disposal of dying cells at all stages of cell death, in particular plasma membrane-damaged cells such as late apoptotic and necrotic cells. This review provides an overview of the molecular mechanisms and the immunological outcomes of late apoptotic/necrotic cell removal and highlights the striking similarities between late apoptotic/necrotic cell and pathogen clearance. The immune system is constantly under pressure to accurately distinguish foreign materials or pathogens (non-self) from normal healthy tissues (self), and make an appropriate immune response to non-self molecules through a range of effector mechanisms. It is equally important for the immune system to distinguish healthy viable cells (self) from dying cells (altered-self) during the course of tissue remodelling or tissue injury to prevent the release of intracellular molecules that may damage neighbouring cells or stimulate an immunogenic response against self (i.e., an autoimmune response). Professional phagocytes of the innate immune system use a broad range of germline-encoded receptors and opsonins to discriminate viable cells from pathogens and dying cells, and aid the removal of non-self and altered-self through phagocytosis.1,2 Not surprisingly, impairment of phagocytosis due to a deficiency in key phagocytic components such as C1q, one of the first components of the classical complement cascade, has been implicated in an increased susceptibility to bacterial infection 3 as well as in the development of autoimmune diseases such as systemic lupus erythematosus (SLE).4 Therefore, understanding the molecular mechanisms of phagocytosis will provide new insights into numerous physiological and pathological processes.Under normal physiological conditions, cells of a multicellular organism predominantly die through the well-defined process known as apoptosis or programmed cell death (see Elmore 5 for an extensive review). During different stages of apoptotic cell death, a precise set of morphological and These authors contributed equally to this work.

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“…They represent a family of proteins with a range of protective bioactivities and are classified into several classes including IgM, IgA, IgG, IgE and IgD (Mix et al, 2006). IgG is the primary immunoglobulin present in ruminant milk, in contrast to IgA being the key immunoglobulin present in human milk (Stewlagen et al, 2009).…”

Section: Page189mentioning

confidence: 99%