Annexin A1, calreticulin and high mobility group box 1 are elevated in secondary progressive multiple sclerosis: Does immunogenic cell death occur in multiple sclerosis?

Introduction: Multiple sclerosis (MS) is a chronic neuroinflammatory diseases characterized by demyelination of the nerve fibers. Immunogenic cell death (ICD) is a process, during which damaged and stressed cells release danger-associated molecular patterns (DAMPs) activating immune responses. This study aimed to elucidate the induction of ICD in MS diseases. Methods: To achieve this goal, the level of DAMPs including Annexin A1 (ANXA1), calreticulin and HMGB1 was measured in the cerebrospinal fluid (CSF) of a secondary progressive multiple sclerosis (SPMS) patient in comparison to control group. Results: Results showed significant upregulation (more than two-fold) of ANXA1, calreticulin (CRT) and HMGB1 in the CSF of the patient. Conclusion: Although further studies are suggested in this regard, this data could imply induction of ICD in MS. The proposed ICD might trigger immune response against neural cells resulting in neuroinflammation and demyelination in CNS in MS. Our observation could suggest inclusion of ICD interfering treatments in routine MS therapy.