[1-3] Material used for this study contained a small fraction of free
Fc fragment. Triple-angle light scattering data indicated that the Fab fragment of NISTmAb sample was in a monomeric state [2, 3].
In future, IVIG preparations containing a higher proportion of
Fc fragments with terminal sialic acid residues may be even more effective.
Moreover, while egg proteins can trigger allergic reactions in some people, and the egg antivenins still retain their
Fc fragments, the Wisconsin team anticipates no serious reactions to their product.
In this study, we have fused the extracellular domain of CTLA-4 to the
Fc fragment of the human IgG1 antibody.
[4] Human genes: GALC, galactosylceramidase; ACADM, acyl-CoA dehydrogenase, C-4 to C-12 straight chain; ACADVL, acyl-CoA dehydrogenase, very long chain; GALT, galactose-1-phosphate uridyl transferase; PAH, phenylalanine hydroxylase; FCGR2A,
Fc fragment of IgG, low affinity IIa, receptor (CD32); RPP30, ribonuclease P/MRP 30kDa subunit.
In intact antibodies, that amino acid portion -- called the
Fc fragment -- normally mediates two powerful immune responses: It helps killer white blood cells recognize and ingest antibody-bound foreign invaders and it triggers a process known as complement activation that destroys those invaders by chemical dissolution.
Human Del-1, ICAM-1 fused to the
Fc fragment of IgG (ICAM-1-Fc), and Fc protein control were purchased from R&D Systems, whereas Del-1-Fc was prepared in our laboratory as follows.
Because rhP/Fc is conjugated with an
Fc fragment of IgG, to evaluate the concentrations of rhP/Fc, we used a colorimetric Fc quantification assay set generally used to estimate IgG concentration in serum.
[4] Human genes: IGHG1 human IgG1 heavy chain constant region; IGHG4 human IgG4 heavy chain constant region; and IGHE, human IgE heavy chain constant region; FCERIA,
Fc fragment of IgE, high affinity I, receptor for; alpha polypepfide; FCER1G,
Fc fragment of IgE, high affinity I, receptor for; gamma polypepfide; MS4A2, membrane-spanning 4-domains, subfamily A, member 2 (
Fc fragment of IgE, high affinity I, receptor for beta polypeptide).
Thirteen samples were found to contain heterophilic antibodies binding to the [F(ab').sub.2] fragment, whereas the remaining 331 samples contained heterophilic antibodies directed against the murine
Fc fragment.
Humanization of animal antibodies (15) and modification of assay antibodies by removal of the
Fc fragment (16) are well-known methods that often dramatically reduce interference.
Initial studies showed that this interference mostly could be solved by the removal of the
Fc fragment from the capture antibody, an indication of the presence of heterophilic antibodies.