scholarly journals Heterogeneity of human circulating anticoagulants against antihemophilic factor (factor VIII)

Blood ◽  
1975 ◽  
Vol 46 (3) ◽  
pp. 409-416 ◽  
Author(s):  
MC Poon ◽  
AC Wine ◽  
OD Ratnoff ◽  
GM Bernier

Abstract The heterogeneity of human circulating anticoagulants against antihemophilic factor (AHF, factor VIII) observed in seven patients, both with and without classic hemophilia, was investigated by neutralization of their activity with antiserums directed to whole IgG and to lambda and kappa light chains. All seven anticoagulants were immunoglobulins. Six appeared to contain both kinds of light chains, although the dual light chain composition of two of these could be demonstrated only at high concentration of antiserum. In one circulating anticoagulant, light chain specificity could not be demonstrated with small amounts of antiserum, and with larger amounts, only lambda light chain specificity was revealed. Whether or not this circulating anticoagulant really contained a single light chain type could not be ascertained with our technique. The evidence presented suggested that circulating anticoagulant antibodies against AHF are polyclonal in nature.

Blood ◽  
1975 ◽  
Vol 46 (3) ◽  
pp. 409-416
Author(s):  
MC Poon ◽  
AC Wine ◽  
OD Ratnoff ◽  
GM Bernier

The heterogeneity of human circulating anticoagulants against antihemophilic factor (AHF, factor VIII) observed in seven patients, both with and without classic hemophilia, was investigated by neutralization of their activity with antiserums directed to whole IgG and to lambda and kappa light chains. All seven anticoagulants were immunoglobulins. Six appeared to contain both kinds of light chains, although the dual light chain composition of two of these could be demonstrated only at high concentration of antiserum. In one circulating anticoagulant, light chain specificity could not be demonstrated with small amounts of antiserum, and with larger amounts, only lambda light chain specificity was revealed. Whether or not this circulating anticoagulant really contained a single light chain type could not be ascertained with our technique. The evidence presented suggested that circulating anticoagulant antibodies against AHF are polyclonal in nature.


Blood ◽  
1977 ◽  
Vol 49 (5) ◽  
pp. 807-817 ◽  
Author(s):  
MB Hultin ◽  
FS London ◽  
SS Shapiro ◽  
WJ Yount

Abstract Previous studies using immunoneutralization techniques have shown that many factor VIII inhibitors are IgG antibodies of a single light chain type. We have investigated this apparent homogeneity by immunoneutralization assay and liquid isoelectric focusing of inhibitor fractions from five hemophiliacs and two nonhemophiliacs. By immunoneutralization assay, inhibitors from four hemophiliacs and one nonhemophiliac were exclusively k light chain type: the fifth hemophilic inhibitor was predominantly k1 and the second nonhemophilic inhibitor was a mixture of k and gamma. However, heavy chain subtyping of the six predominantly or exclusively k inhibitors showed all to be mixtures of IgG4 and IgG1. By isoelectric focusing, two inhibitors showed multiple peaks of activity between pH 5 and 9. The remaining five showed predominant peaks of activity, which were solely IgGk1 between pH 5.8 and 7, with smaller peaks between pH 7 and 9. The most acidic major peak, focusing at pH 6, was IgG4 in the three cases tested. Two of these acidic peaks neutralized factor VIII more efficiently than other peaks in the same focusing profiles, suggesting greater affinity for factor VIII. These studies demonstrate that factor VIII inhibitors are composed of heterogenous subpopulations of immunoglobulins which can be separated by isoelectric focusing.


Blood ◽  
1984 ◽  
Vol 63 (5) ◽  
pp. 1241-1244 ◽  
Author(s):  
J Jansen ◽  
HR Schuit ◽  
J Hermans ◽  
W Hijmans

Abstract Hairy cell leukemia (HCL) is a usually chronic B cell lymphoproliferative disorder. To evaluate the prognostic significance of the various heavy and light chain determinants of the surface immunoglobulins (slg), we analyzed the clinical data and immunologic phenotype of 64 patients with HCL. Sixty-two of the 64 patients showed slg, which was invariably of only one light chain type (kappa 33, lambda 29). The actuarial survival of the cases expressing kappa-light chains was significantly better than those with lambda-light chains (p less than 0.002). This difference persisted when only cases with gamma or alpha gamma heavy chains were considered. No differences between the kappa and lambda-subgroups were discovered with respect to parameters of clinical importance. The various heavy chain classes of slg did not correlate significantly with the survival time. These results suggest that the immunologic phenotype, in particular the light chain type, may be a prognostic factor in patients with HCL.


1994 ◽  
Vol 102 (1-2) ◽  
pp. 161-166 ◽  
Author(s):  
Mark F. Prummel ◽  
Stefano Portolano ◽  
Guiseppe Costante ◽  
Basil Rapoport ◽  
Sandra M. McLachlan

1983 ◽  
Vol 157 (1) ◽  
pp. 337-341 ◽  
Author(s):  
F K Stevenson ◽  
G T Stevenson ◽  
A L Tutt

An investigation has been made into the ability of human neoplastic B lymphocytes expressing surface IgM and IgD to export IgD in culture. Cells that expressed surface Ig of the lambda light chain type frequently exported IgD (10/12 patients), whereas cells expressing surface Ig of the kappa light chain type exported no IgD, although most (8/11 patients) were able to export IgM. It appears, therefore, that in most of the 23 cases studied, cells synthesizing IgD with lambda light chains can both express and export IgD, whereas those synthesizing IgD kappa can only insert it into the surface membrane. This finding and the known preponderance of lambda in plasma IgD imply that the possession of a lambda chain facilitates the IgD secretory pathway, a conclusion that implicates a control mechanism subsequent to the surface/secretory dichotomy arising from different splicings of heavy chain messenger RNA.


Blood ◽  
1981 ◽  
Vol 57 (1) ◽  
pp. 192-195 ◽  
Author(s):  
M Nicholls ◽  
PC Vincent ◽  
E Repka ◽  
J Saunders ◽  
FW Gunz

Abstract B lymphocyte surface immunoglobulins (Smlg) were studied in 24 patients with multiple myeloma by means of anti-isotypic antisera, and their heavy and light chain isotypes were compared in each patient with those of the paraprotein. In 21 patients, lymphocyte Smlg consisted of only one light chain type, and in 16 of only 1 heavy chain type. However, the Smlg and paraprotein heavy and light chain types were identical in only 5 patients while in 6 they differed in heavy and light chain types, in 7 in light chain type, and in 4 in heavy chain type. In 2 patients with light chain myeloma, Smlg light chains were isotypically the same as the paraprotein. Isotypic discordance between paraprotein and Smlg may signify the proliferation of a second malignant clone with failure to differentiate into secreting plasma cells. Alternatively, it is conceivable that the lymphocyte Smlg could have the same idiotypic specificity as the paraprotein despite the isotypic differences, but this will require further studies using anti-idiotypic antisera.


Blood ◽  
1977 ◽  
Vol 49 (5) ◽  
pp. 807-817 ◽  
Author(s):  
MB Hultin ◽  
FS London ◽  
SS Shapiro ◽  
WJ Yount

Previous studies using immunoneutralization techniques have shown that many factor VIII inhibitors are IgG antibodies of a single light chain type. We have investigated this apparent homogeneity by immunoneutralization assay and liquid isoelectric focusing of inhibitor fractions from five hemophiliacs and two nonhemophiliacs. By immunoneutralization assay, inhibitors from four hemophiliacs and one nonhemophiliac were exclusively k light chain type: the fifth hemophilic inhibitor was predominantly k1 and the second nonhemophilic inhibitor was a mixture of k and gamma. However, heavy chain subtyping of the six predominantly or exclusively k inhibitors showed all to be mixtures of IgG4 and IgG1. By isoelectric focusing, two inhibitors showed multiple peaks of activity between pH 5 and 9. The remaining five showed predominant peaks of activity, which were solely IgGk1 between pH 5.8 and 7, with smaller peaks between pH 7 and 9. The most acidic major peak, focusing at pH 6, was IgG4 in the three cases tested. Two of these acidic peaks neutralized factor VIII more efficiently than other peaks in the same focusing profiles, suggesting greater affinity for factor VIII. These studies demonstrate that factor VIII inhibitors are composed of heterogenous subpopulations of immunoglobulins which can be separated by isoelectric focusing.


Blood ◽  
1981 ◽  
Vol 57 (1) ◽  
pp. 192-195
Author(s):  
M Nicholls ◽  
PC Vincent ◽  
E Repka ◽  
J Saunders ◽  
FW Gunz

B lymphocyte surface immunoglobulins (Smlg) were studied in 24 patients with multiple myeloma by means of anti-isotypic antisera, and their heavy and light chain isotypes were compared in each patient with those of the paraprotein. In 21 patients, lymphocyte Smlg consisted of only one light chain type, and in 16 of only 1 heavy chain type. However, the Smlg and paraprotein heavy and light chain types were identical in only 5 patients while in 6 they differed in heavy and light chain types, in 7 in light chain type, and in 4 in heavy chain type. In 2 patients with light chain myeloma, Smlg light chains were isotypically the same as the paraprotein. Isotypic discordance between paraprotein and Smlg may signify the proliferation of a second malignant clone with failure to differentiate into secreting plasma cells. Alternatively, it is conceivable that the lymphocyte Smlg could have the same idiotypic specificity as the paraprotein despite the isotypic differences, but this will require further studies using anti-idiotypic antisera.


1995 ◽  
Vol 32 (14-15) ◽  
pp. 1157-1169 ◽  
Author(s):  
Stefano Portolano ◽  
Mark F. Prummel ◽  
Basil Rapoport ◽  
Sandra M. McLachlan

Blood ◽  
1984 ◽  
Vol 63 (5) ◽  
pp. 1241-1244 ◽  
Author(s):  
J Jansen ◽  
HR Schuit ◽  
J Hermans ◽  
W Hijmans

Hairy cell leukemia (HCL) is a usually chronic B cell lymphoproliferative disorder. To evaluate the prognostic significance of the various heavy and light chain determinants of the surface immunoglobulins (slg), we analyzed the clinical data and immunologic phenotype of 64 patients with HCL. Sixty-two of the 64 patients showed slg, which was invariably of only one light chain type (kappa 33, lambda 29). The actuarial survival of the cases expressing kappa-light chains was significantly better than those with lambda-light chains (p less than 0.002). This difference persisted when only cases with gamma or alpha gamma heavy chains were considered. No differences between the kappa and lambda-subgroups were discovered with respect to parameters of clinical importance. The various heavy chain classes of slg did not correlate significantly with the survival time. These results suggest that the immunologic phenotype, in particular the light chain type, may be a prognostic factor in patients with HCL.


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