Inverse correlation between IgG-antihinge region and antierythrocyte autoantibody in chronic benign and malignant cold agglutination.
Previous reports provided evidence of an immunosuppressive role of natural anti-F(ab')2 antibodies. If suppressive anti-F(ab')2 antibodies also regulated the autoantibody production in cold agglutination, one would expect high titers of anti-F(ab')2 to be associated with low titers of cold agglutinins. Indeed, our previous studies revealed an inverse correlation between IgG-anti-F(ab')2 and cold agglutinins. Many previous experiments focused on anti-F(ab')2 of an antiidiotypic nature. Recent epitope mapping showed that anti-F(ab')2 of healthy persons is not an antiidiotype but recognizes a hinge region sequence. We attempted to answer the question whether this IgG-antihinge antibody is responsible for the previously described association between anti-F(ab')2 and cold agglutinins. IgG-antihinge and IgG-anti-F(ab')2 antibody was determined and statistically analyzed in the serum of 334 patients with cold agglutination. Our experiments revealed a strong correlation between the concentrations of antihinge and the previously described anti-F(ab')2 antibody. The anti-F(ab')2 activity was competitively inhibited by a synthetic hinge peptide. Moreover, patients with high antihinge titers had low cold agglutinin titers, and vice versa. A stratification according to cold agglutinin specificity and disease etiology showed that the inverse correlation is present only in anti-I and anti-i patients suffering from monoclonal B-lymphocyte proliferation. In conclusion, our results confirm the correlation previously described for anti-F(ab')2 antibody and antierythrocyte autoantibody and define for the first time an association between an idiotype-independent anti-IgG autoantibody and cold agglutinin.
Terness
P
P
University of Heidelberg, Department of Transplantation Immunology, Germany.
Kirschfink
M
M
Navolan
D
D
Moroder
L
L
Siedler
F
F
Drugarin
D
D
Schneider
F
F
Dufter
C
C
Kohl
I
I
Welschof
M
M
Opelz
G
G
Roelcke
D
D
D000328:Adult; D000373:Agglutinins / Q000096:biosynthesis / Q000097:blood*; D000744:Anemia, Hemolytic, Autoimmune / Q000097:blood* / Q000276:immunology; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D001323:Autoantibodies / Q000097:blood* / Q000502:physiology; D003080:Cold Temperature; D003450:Cryoglobulins; D004912:Erythrocytes / Q000276:immunology*; D006388:Hemagglutinins / Q000096:biosynthesis / Q000097:blood*; D006801:Humans; D007048:I Blood-Group System / Q000276:immunology; D007128:Immunoglobulin Fragments / Q000096:biosynthesis / Q000097:blood* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood* / Q000276:immunology; D007231:Infant, Newborn; D010446:Peptide Fragments / Q000276:immunology*
D000373:Agglutinins; D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D003450:Cryoglobulins; D006388:Hemagglutinins; D007048:I Blood-Group System; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D010446:Peptide Fragments; C029443:cold agglutinins