Patients with Multiple Myeloma Develop SOX2-Specific Autoantibodies after Allogeneic Stem Cell Transplantation

الملخص EN

The occurrence of SOX2-specific autoantibodies seems to be associated with an improved prognosis in patients with monoclonal gammopathy of undetermined significance (MGUS).

However, it is unclear if SOX2-specific antibodies also develop in established multiple myeloma (MM).

Screening 1094 peripheral blood (PB) sera from 196 MM patients and 100 PB sera from healthy donors, we detected SOX2-specific autoantibodies in 7.7% and 2.0% of patients and donors, respectively.

We identified SOX2211–230 as an immunodominant antibody-epitope within the full protein sequence.

SOX2 antigen was expressed in most healthy tissues and its expression did not correlate with the number of BM-resident plasma cells.

Accordingly, anti-SOX2 immunity was not related to SOX2 expression levels or tumor burden in the patients’ BM.

The only clinical factor predicting the development of anti-SOX2 immunity was application of allogeneic stem cell transplantation (alloSCT).

Anti-SOX2 antibodies occurred more frequently in patients who had received alloSCT (n=74).

Moreover, most SOX2-seropositive patients had only developed antibodies after alloSCT.

This finding indicates that alloSCT is able to break tolerance towards this commonly expressed antigen.

The questions whether SOX2-specific autoantibodies merely represent an epiphenomenon, are related to graft-versus-host effects or participate in the immune control of myeloma needs to be answered in prospective studies.