Contributions
Abstract: P569
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Evidence suggests LLPCs in the CNS of patients with MS contribute to the propagation and perpetuation of disease.
The plasmablasts that origínate in the secondary lymphoid nodules have the ability to migrate to the bone marrow or to inflamed tissue, where they compete for niches that provide a suitable environment for subsequent survival as long lived plasma cells (LLPCs). LLPCs are not cycling cells and they are responsible for antibody secretion. LLPCs identified in the niches of the bone marrow are CD19-CD38 highCD138+CD28+HLA-DRlowCD56+/-CD95low ↑BCL2 ↓Ki67. Non-proliferating CD 138+ (Ki67-) plasma cells have been found in the cerebral parenchyma, meninges and perivascular spaces of patients with MS, suggestive of LLPCs. Survival of LLPCs depend on the presence of APRIL, IL-6 and CXCL12 in specialized niches.
Reviewed medical literature related to the role of LLPCs in oligoclonal bands production and to the different outcomes of determination of oligoclonal bands in CSF from patients with MS after exposure to different immunotherapy.
Remarkable findings were reported in 1) a patient with RRMS with a clinical course refractory to therapy with beta interferon, subsequently found to be responsive to rituximab but ultimately developing SPMS with significant lesion load in the spinal cord. Oligoclonal bands were positive in CSF during the whole course of disease. 2) Negative oligoclonal bands in CSF among 55% of 24 MS patients who were treated with natalizumab for 24 months. 3) The persistence of CSF oligoclonal bands among 88% of SPMS patients treated with autologous stem cell transplant that included immunoablative conditioning regime with antithymocyte globulin (ATG), cyclophosphamide and total body irradiation.
LLPCs in the CNS compartment have the ability to produce antibodies for very long periods of time, resulting in perpetuation of oligoclonal bands production, and they are resistant to the any therapeutic attempt (systemic or intrathecal) with B-cell depleting therapy. Potential therapeutic strategies to ameliorate presence and effect of LLPCs in MS could include lenanidomide, a potent anti-inflammatory thalidomide analog that has been able to inhibit LLPCs in vitro. Additional therapeutic alternatives may include the use of ATG, proteasome inhibitors, targeting survival factors, targeting plasma cell homing, and targeting cell surface molecules.
Disclosure: Dr. Mora is a member of the Data & Safety Monitoring Board for the NINDS/NIH study NS003055-08/NS003056-08. He received no compensation for his participation in that study. ACL does not report any competing interests.
Abstract: P569
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Evidence suggests LLPCs in the CNS of patients with MS contribute to the propagation and perpetuation of disease.
The plasmablasts that origínate in the secondary lymphoid nodules have the ability to migrate to the bone marrow or to inflamed tissue, where they compete for niches that provide a suitable environment for subsequent survival as long lived plasma cells (LLPCs). LLPCs are not cycling cells and they are responsible for antibody secretion. LLPCs identified in the niches of the bone marrow are CD19-CD38 highCD138+CD28+HLA-DRlowCD56+/-CD95low ↑BCL2 ↓Ki67. Non-proliferating CD 138+ (Ki67-) plasma cells have been found in the cerebral parenchyma, meninges and perivascular spaces of patients with MS, suggestive of LLPCs. Survival of LLPCs depend on the presence of APRIL, IL-6 and CXCL12 in specialized niches.
Reviewed medical literature related to the role of LLPCs in oligoclonal bands production and to the different outcomes of determination of oligoclonal bands in CSF from patients with MS after exposure to different immunotherapy.
Remarkable findings were reported in 1) a patient with RRMS with a clinical course refractory to therapy with beta interferon, subsequently found to be responsive to rituximab but ultimately developing SPMS with significant lesion load in the spinal cord. Oligoclonal bands were positive in CSF during the whole course of disease. 2) Negative oligoclonal bands in CSF among 55% of 24 MS patients who were treated with natalizumab for 24 months. 3) The persistence of CSF oligoclonal bands among 88% of SPMS patients treated with autologous stem cell transplant that included immunoablative conditioning regime with antithymocyte globulin (ATG), cyclophosphamide and total body irradiation.
LLPCs in the CNS compartment have the ability to produce antibodies for very long periods of time, resulting in perpetuation of oligoclonal bands production, and they are resistant to the any therapeutic attempt (systemic or intrathecal) with B-cell depleting therapy. Potential therapeutic strategies to ameliorate presence and effect of LLPCs in MS could include lenanidomide, a potent anti-inflammatory thalidomide analog that has been able to inhibit LLPCs in vitro. Additional therapeutic alternatives may include the use of ATG, proteasome inhibitors, targeting survival factors, targeting plasma cell homing, and targeting cell surface molecules.
Disclosure: Dr. Mora is a member of the Data & Safety Monitoring Board for the NINDS/NIH study NS003055-08/NS003056-08. He received no compensation for his participation in that study. ACL does not report any competing interests.