Anti-Erythroblast Autoimmunity in Pediatric Myelodysplatic Syndromes.

Introduction: Myelodysplatic syndromes (MDS) are characterized by ineffective and dysplastic hematopoiesis and peripheral cytopenias. Moreover, autoimmune phenomena, mainly directed against RBC, are described in early MDS, i.e. refractory anemia (RA) and RA with ringed sideroblasts (RARS). We already reported an autoimmune reactivity against erythroblasts in 50% of RA and RARS adult patients, along with peripheral signs of hemolysis, increased BM erythroblasts; and efficacy of steroid therapy. It has become evident that there are significant differences between MDS in children and adults. Most importantly, the cure is the aim of therapy in all children with MDS, while therapeutic possibilities are often limited in adults. MDS and myeloproliferative disorders are rare in childhood and there is no widely accepted system for their diagnosis and classification. Aims of this study were:

1. To evaluate BM autoimmunity in 9 pediatric patients with MDS by the same method used in adults, named mitogen-stimulated-direct antiglobulin test (MS-DAT),

2. to correlate BM MS-DAT positivity with clinical parameters and therapy.

Methods: MS-DAT was performed by stimulating BM with PMA and PHA and antibodies were detected in supernatants by competitive solid phase ELISA.

Results: We demonstrated the presence of anti-erythroblast autoimmunity in roughly half of pediatric MDS patients, as already reported in adult MDS. More precisely, 4 out of 9 patients showed positive MS-DAT in BM. At variance with adult MDS, positive patients do not show increased erythroblast counts and peripheral signs of hemolysis (i.e higher reticulocytes, indirect bilirubin, and LDH, and lower haptoglobin) compared with MS-DAT negative ones. One of the four patients with anti-erithroblasts autoimmunity has RA, the other three show peripheral and medullary signs of refractory cytopenia with multilineage dysplasia (RCMD). Two out of four were successfully treated with steroid therapy (with a follow up respectively of 6 and 1 months).

Discussion: Although the short follow up and the limited number of patients does not allow definitive conclusions, we retain useful to investigate anti-erythroid autoimmunity in all pediatric MDS in order to identify selected patients with low risk MDS who display autoimmune phenomena. In these cases immunosoppressive therapy may be an effective treatment option.