Blood, Vol. 94 No. 11 (December 1), 1999:
pp. 3683-3693
Erythroblastic Synartesis: An Auto-immune Dyserythropoiesis
Elisabeth M. Cramer,
Isabel Garcia,
Jean-Marc Massé,
Jean-Marc Zini,
Patrick Lambin,
Eric Oksenhendler,
Fadila Souni,
Mark Smith,
Georges Flandrin,
Janine Breton-Gorius,
Gérard Tobelem, and
Nicole Casadevall
From Services d'Hématologie Biologique et Clinique,
Hôpital Lariboisière, Paris, France; Service
d'Immunologie-Hématologie, Hôpital Raymond Poincaré,
Paris, France; INSERM U. 474, Hôpital Henri Mondor,
Créteil, INTS, Paris, France; Haemophilia Centre, St Thomas'
Hospital, London, UK; Service d'Immuno-Hématologie Clinique,
Hôpital Saint Louis, Paris, France; and Service
d'Hématologie Biologique, Hôpital Necker-Enfants Malades,
Paris, France.
Erythroblastic synartesis is a rare form of acquired
dyserythropoiesis, first described by Breton-Gorius et al in 1973. This syndrome is characterized by the presence of septate-like membrane junctions and "glove finger" invaginations between erythroblasts, which are very tightly linked together. This phenomenon, responsible for ineffective erythropoiesis, leads to an isolated severe anemia with
reticulocytopenia. In the following report, we describe 3 new cases of
erythroblastic synartesis associated with dysimmunity and monoclonal
gammapathy. In all cases, the diagnosis was suggested by characteristic
morphological appearance of bone marrow smears, and further confirmed
by electron microscopy. Ultrastructural examination of abnormal
erythroblast clusters showed that these cells were closely approximated
with characteristic intercellular membrane junctions. The pathogenesis
of the dyserythropoiesis was modeled in vitro using crossed
erythroblast cultures and immunoelectron microscopy: when cultured in
the presence of autologous serum, the erythroblasts from the patients
displayed synartesis, whereas these disappeared when cultured in normal
serum. Moreover, synartesis of normal erythroblasts were induced by the
patient IgG fraction. Immunogold labeling showed that the monoclonal
IgG were detected in, and restricted to, the synartesis. A discrete
monoclonal plasmacytosis was also found in the patient bone marrow. The
adhesion receptor CD36 appeared to be concentrated in the junctions,
suggesting that it might be involved in the synartesis. These
experiments indicated that a monoclonal serum immunoglobulin (IgG in
the present cases) directed at erythroblast membrane antigen was
responsible for the erythroblast abnormalities. Specific therapy of the
underlying lymphoproliferation was followed by complete remission of
the anemia in these cases.
