Autoantibodies to c1 inhibitor in acquired cl inhibitor deficiency

significance of associated m components and affinity characteristics

Marcp Cicardi, Andrea Beretta, Monica Colombo, Daniela Gioffré, Massimo Cugno, Angelo Agostoni

Research output: Contribution to journalArticle

Abstract

Autoantibodies to Cl inhibitor (Cl-INH)and various type of B cell proliferative disorders are the conditions most frequently described in patients with acquired Cl-INH deficiency who suffer from recurrent angioedema symptoms (Acquired Angioedema, AAE). Whether those 2 conditions may coexist remains to be elucidated. We report 13 patients with AAE and the affinity characteristics of the anti-Cl-INH autoantibodies, isolated from serum of 6 of them. No associated disease was identified in 3 patients, 1 had liver idatidosis, 1 breast cancer, 1 chronic lymphocytk leukemia, 7 serum M components that in 2 fulfilled the criteria for diagnosis of Waldenstroem macroglobulinemia. Cl-INH and C4 were constantly low at repeated controls in all patients. Anti-Cl-INH immunoglobulins (Igs) were measured both as Igs binding to Cl-INH immobilized onto microtiter plates (ELISA) and as Igs blocking the capacity of Cl-INH to inhibit the esterolytic activity of its target protease Cls (functional assay). In 12 patients both assays were positive, in 1 anti-ClINH Igs were detectable only by functional assay. Immunoblotting analysis of SDS-PAGE separated plasma, showed that in the 12 patients with autoantibodies, but not in the 1 without, Cl-INH circulated in its cleaved form of 96 kD. Agarose electrophoresis of plasma of 7 patients with paraproteins was transferred onto Immobilon sheets and blotted with purified Cl-INH that was subsequently revealed by monospecific antibody: in 5 plasma the bands representing the M components were able to bind Cl-INH. To evaluate the antigen/autoantibody binding-affinity we measured the amount of purified Cl-INH, added in fluid phase to the affinity-purified autoantibody, necessary to saturate its binding to the immobilized protein. The molar ratio of Cl-INH-autoantibody interaction, measured with the autoanti bodies of 6 different patients, ranged between 28 and 770. In conclusion the majority of our AAE patients have autoanti bodies to Cl-INH. When proliferating B cell clones secrete monoclonal immunoglobulins they frequently represent the autoantibodies to Cl-INH. These autoantibodies have variable, but generally very low affinities for the soluble antigen.

Original languageEnglish
JournalFASEB Journal
Volume10
Issue number6
Publication statusPublished - 1996

Fingerprint

autoantibodies
Autoantibodies
Immunoglobulins
immunoglobulins
Myeloma Proteins
Assays
Plasmas
B-lymphocytes
Clone cells
assays
B-Lymphocytes
Immobilized Proteins
Paraproteins
Antigens
antigens
Waldenstrom Macroglobulinemia
Angioedema
Electrophoresis
Liver
Sepharose

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Autoantibodies to c1 inhibitor in acquired cl inhibitor deficiency : significance of associated m components and affinity characteristics. / Cicardi, Marcp; Beretta, Andrea; Colombo, Monica; Gioffré, Daniela; Cugno, Massimo; Agostoni, Angelo.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

Cicardi, Marcp ; Beretta, Andrea ; Colombo, Monica ; Gioffré, Daniela ; Cugno, Massimo ; Agostoni, Angelo. / Autoantibodies to c1 inhibitor in acquired cl inhibitor deficiency : significance of associated m components and affinity characteristics. In: FASEB Journal. 1996 ; Vol. 10, No. 6.
@article{3a9fa8a9bfc14054976c249edb262428,
title = "Autoantibodies to c1 inhibitor in acquired cl inhibitor deficiency: significance of associated m components and affinity characteristics",
abstract = "Autoantibodies to Cl inhibitor (Cl-INH)and various type of B cell proliferative disorders are the conditions most frequently described in patients with acquired Cl-INH deficiency who suffer from recurrent angioedema symptoms (Acquired Angioedema, AAE). Whether those 2 conditions may coexist remains to be elucidated. We report 13 patients with AAE and the affinity characteristics of the anti-Cl-INH autoantibodies, isolated from serum of 6 of them. No associated disease was identified in 3 patients, 1 had liver idatidosis, 1 breast cancer, 1 chronic lymphocytk leukemia, 7 serum M components that in 2 fulfilled the criteria for diagnosis of Waldenstroem macroglobulinemia. Cl-INH and C4 were constantly low at repeated controls in all patients. Anti-Cl-INH immunoglobulins (Igs) were measured both as Igs binding to Cl-INH immobilized onto microtiter plates (ELISA) and as Igs blocking the capacity of Cl-INH to inhibit the esterolytic activity of its target protease Cls (functional assay). In 12 patients both assays were positive, in 1 anti-ClINH Igs were detectable only by functional assay. Immunoblotting analysis of SDS-PAGE separated plasma, showed that in the 12 patients with autoantibodies, but not in the 1 without, Cl-INH circulated in its cleaved form of 96 kD. Agarose electrophoresis of plasma of 7 patients with paraproteins was transferred onto Immobilon sheets and blotted with purified Cl-INH that was subsequently revealed by monospecific antibody: in 5 plasma the bands representing the M components were able to bind Cl-INH. To evaluate the antigen/autoantibody binding-affinity we measured the amount of purified Cl-INH, added in fluid phase to the affinity-purified autoantibody, necessary to saturate its binding to the immobilized protein. The molar ratio of Cl-INH-autoantibody interaction, measured with the autoanti bodies of 6 different patients, ranged between 28 and 770. In conclusion the majority of our AAE patients have autoanti bodies to Cl-INH. When proliferating B cell clones secrete monoclonal immunoglobulins they frequently represent the autoantibodies to Cl-INH. These autoantibodies have variable, but generally very low affinities for the soluble antigen.",
author = "Marcp Cicardi and Andrea Beretta and Monica Colombo and Daniela Gioffr{\'e} and Massimo Cugno and Angelo Agostoni",
year = "1996",
language = "English",
volume = "10",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "6",

}

TY - JOUR

T1 - Autoantibodies to c1 inhibitor in acquired cl inhibitor deficiency

T2 - significance of associated m components and affinity characteristics

AU - Cicardi, Marcp

AU - Beretta, Andrea

AU - Colombo, Monica

AU - Gioffré, Daniela

AU - Cugno, Massimo

AU - Agostoni, Angelo

PY - 1996

Y1 - 1996

N2 - Autoantibodies to Cl inhibitor (Cl-INH)and various type of B cell proliferative disorders are the conditions most frequently described in patients with acquired Cl-INH deficiency who suffer from recurrent angioedema symptoms (Acquired Angioedema, AAE). Whether those 2 conditions may coexist remains to be elucidated. We report 13 patients with AAE and the affinity characteristics of the anti-Cl-INH autoantibodies, isolated from serum of 6 of them. No associated disease was identified in 3 patients, 1 had liver idatidosis, 1 breast cancer, 1 chronic lymphocytk leukemia, 7 serum M components that in 2 fulfilled the criteria for diagnosis of Waldenstroem macroglobulinemia. Cl-INH and C4 were constantly low at repeated controls in all patients. Anti-Cl-INH immunoglobulins (Igs) were measured both as Igs binding to Cl-INH immobilized onto microtiter plates (ELISA) and as Igs blocking the capacity of Cl-INH to inhibit the esterolytic activity of its target protease Cls (functional assay). In 12 patients both assays were positive, in 1 anti-ClINH Igs were detectable only by functional assay. Immunoblotting analysis of SDS-PAGE separated plasma, showed that in the 12 patients with autoantibodies, but not in the 1 without, Cl-INH circulated in its cleaved form of 96 kD. Agarose electrophoresis of plasma of 7 patients with paraproteins was transferred onto Immobilon sheets and blotted with purified Cl-INH that was subsequently revealed by monospecific antibody: in 5 plasma the bands representing the M components were able to bind Cl-INH. To evaluate the antigen/autoantibody binding-affinity we measured the amount of purified Cl-INH, added in fluid phase to the affinity-purified autoantibody, necessary to saturate its binding to the immobilized protein. The molar ratio of Cl-INH-autoantibody interaction, measured with the autoanti bodies of 6 different patients, ranged between 28 and 770. In conclusion the majority of our AAE patients have autoanti bodies to Cl-INH. When proliferating B cell clones secrete monoclonal immunoglobulins they frequently represent the autoantibodies to Cl-INH. These autoantibodies have variable, but generally very low affinities for the soluble antigen.

AB - Autoantibodies to Cl inhibitor (Cl-INH)and various type of B cell proliferative disorders are the conditions most frequently described in patients with acquired Cl-INH deficiency who suffer from recurrent angioedema symptoms (Acquired Angioedema, AAE). Whether those 2 conditions may coexist remains to be elucidated. We report 13 patients with AAE and the affinity characteristics of the anti-Cl-INH autoantibodies, isolated from serum of 6 of them. No associated disease was identified in 3 patients, 1 had liver idatidosis, 1 breast cancer, 1 chronic lymphocytk leukemia, 7 serum M components that in 2 fulfilled the criteria for diagnosis of Waldenstroem macroglobulinemia. Cl-INH and C4 were constantly low at repeated controls in all patients. Anti-Cl-INH immunoglobulins (Igs) were measured both as Igs binding to Cl-INH immobilized onto microtiter plates (ELISA) and as Igs blocking the capacity of Cl-INH to inhibit the esterolytic activity of its target protease Cls (functional assay). In 12 patients both assays were positive, in 1 anti-ClINH Igs were detectable only by functional assay. Immunoblotting analysis of SDS-PAGE separated plasma, showed that in the 12 patients with autoantibodies, but not in the 1 without, Cl-INH circulated in its cleaved form of 96 kD. Agarose electrophoresis of plasma of 7 patients with paraproteins was transferred onto Immobilon sheets and blotted with purified Cl-INH that was subsequently revealed by monospecific antibody: in 5 plasma the bands representing the M components were able to bind Cl-INH. To evaluate the antigen/autoantibody binding-affinity we measured the amount of purified Cl-INH, added in fluid phase to the affinity-purified autoantibody, necessary to saturate its binding to the immobilized protein. The molar ratio of Cl-INH-autoantibody interaction, measured with the autoanti bodies of 6 different patients, ranged between 28 and 770. In conclusion the majority of our AAE patients have autoanti bodies to Cl-INH. When proliferating B cell clones secrete monoclonal immunoglobulins they frequently represent the autoantibodies to Cl-INH. These autoantibodies have variable, but generally very low affinities for the soluble antigen.

UR - http://www.scopus.com/inward/record.url?scp=33749102192&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749102192&partnerID=8YFLogxK

M3 - Article

VL - 10

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 6

ER -