Etiologic aspects of cold agglutinin disease: evidence for cytogenetically
defined clones of lymphoid cells and the demonstration that an anti-Pr cold
autoantibody is derived from a chromosomally aberrant B cell clone
LE Silberstein, GA Robertson, AC Harris, L Moreau, E Besa and PC Nowell
This study investigated the clonal nature of cold agglutinin disease in a
series of nine patients, which included the benign or idiopathic form as
well as cases with an underlying lymphoma. Surface marker phenotyping and
karyotypic analysis were performed on peripheral blood lymphocytes. An
increased proportion of B cells was found in four cases and in three of
these patients a monoclonal B cell population was identified with a mu,
kappa phenotype. In the same three cases, as well as an additional patient,
an aberrant karyotype was demonstrated. The cytogenetic abnormality present
in all four cases included trisomy 3; two patients also had a trisomy 12.
One of these four patients had a well-differentiated lymphoma and underwent
a splenectomy. Splenic lymphocytes were transformed with Epstein-Barr virus
and cultured en masse. Eight clones were established producing the same
cold agglutinin with identical specificity as that present in the patient's
plasma. Five of these clones were studied cytogenetically, and all had the
same abnormal karyotype (51,XX,+3,+9,+12,+13,+18) found in peripheral blood
and splenic lymphocytes. Thus, in this case, the cold reactive autoantibody
was produced by the chromosomally abnormal, neoplastic clone of
lymphocytes. Our findings support the view that cold agglutinin disease
represents a spectrum of clonal disorders.
Volume 67,
Issue 6,
pp. 1705-1709,
06/01/1986
Copyright © 1986 by The American Society of Hematology
