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Blocking and Binding Type Antibodies against All Major Vitamin B 12 ‐Binders in a Pernicious Anaemia Serum
Author(s) -
Marcoullis George,
Parmentier Yves,
Nicolas JeanPierre
Publication year - 1979
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1979.tb03715.x
Subject(s) - antibody , chemistry , sephadex , immunoglobulin m , immunoglobulin g , pernicious anaemia , microbiology and biotechnology , blocking antibody , biochemistry , receptor , immunology , medicine , biology , enzyme
S ummary . The simultaneous occurrence of blocking and binding antibodies to intrinsic factor (IF), transcobalamin (TC‐ II, TC I) and other R type vitamin B 12 proteins in the serum of a patient with treated pernicious anaemia (PA) is reported here for the first time. The dialysed and purified immunoglobulin‐G (IgG), but not the immunoglobulin‐M (IgM), from a PA patient neutralized the total unsaturated vitamin B 12 binding capacity (UB 12 BC) of human gastric juice, saliva and serum and also of rabbit serum, suggesting that the PA IgG contained blocking antibodies against, IF, TC II, TC I and other R‐binders. In addition, the PA IgG and IgM preparations contained binding antibodies since they could form macromolecular complexes with 57 Co‐B 12 bound to IF, TC I or TC II so that each one of the latter was totally excluded from Sephadex G‐200. The presence of the binding antibodies was further confirmed by the formation of radioactive precipitation lines on agarose with each one of the vitamin B 12 ‐binders bound to 58 Co‐B 12 . The PA serum did not exhibit any measurable UB 12 BC after dialysis against 7.5 m guanidine‐HCl followed by renaturation with phosphate buffer (pH 7.4). But it did form TC I and TC II complexes with 57 Co‐B 12 when the latter was added during the renaturation step indicating that the serum contained circulating immunoglobulin‐TC complexes. The blocking antibodies should be distinguished from the previously described binding antibodies. The blocking of the binding of vitamin B 12 to TCs resulted in relatively lower serum vitamin B 12 levels in the present case in contrast to the presence of binding antibodies where high serum vitamin B 12 levels have been reported. In addition, the binding antibodies form immunocomplexes with TCs which can easily be detected because they can bind radioactive vitamin B 12 while the corresponding immunocomplexes of blocking antibodies are hidden because they prevent the binding of the vitamin to TCs.