Natalizumab and B cells

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Natalizumab hits plasmablasts…..These are short-lived antibody secreting B cells that form the long lived antibody secreting plasma cells. This study says that antibody levels can be affected, but before we run too scared from getting a COVID-19 vaccine, I would say most people on natalizumab that I have seen, make a COVID-19 B cell response (obviously wait for the data to surface). Although antibody levels dropped in the CNS with long term treatment some antibodies persistented so this is another paper suggesting that it dose not inhibit oligoclonal bands completely

Effects of Natalizumab Therapy on Intrathecal Immunoglobulin G Production Indicate Targeting of Plasmablasts. Miriam Schlüter, Eva Oswald, Stephan Winklmeier, Ingrid Meinl, Joachim Havla, Peter Eichhorn, Edgar Meinl, Tania Kümpfe lNeurol Neuroimmunol Neuroinflamm 2021, 8: e1030; DOI: 10.1212/NXI.0000000000001030

Objectives To evaluate the long-term effects of natalizumab (NTZ) on different features of intrathecal immunoglobulin (Ig) synthesis in patients with multiple sclerosis (MS) and to quantify the expression of α4-integrin in stages of B-cell maturation.

Methods We combined a cross-sectional (49 NTZ-treated MS patients, mean treatment duration 5.1 years, and 47 untreated MS patients) and a longitudinal study (33 patients with MS before and during NTZ, mean treatment duration: 4.8 years), analyzing paired serum and CSF samples for IgG, IgA, and IgM levels, reactivity against selected viruses (measles virus, rubella virus, and varicella zoster virus [MRZ] reaction), and oligoclonal bands (OCBs). Banding patterns before and after therapy were directly compared by isoelectric focusing in 1 patient. In addition, we determined the expression of α4-integrin by FACS analysis on blood-derived B-cell subsets (plasmablasts, memory B cells, and naive B cells) of healthy controls.

Results In serum, NTZ decreased IgM and IgG, but not IgA, levels. IgM hypogammaglobulinemia occurred in 28% of NTZ-treated patients. In CSF, NTZ treatment resulted in a strong reduction of intrathecally produced IgG and, to a lesser extent, IgA, whereas IgM indices [(Ig CSF/Serum)/(Albumin CSF/Serum)] remained largely unchanged. Reduction of the IgG index correlated with NTZ treatment duration, as did serum IgM and IgA levels. MRZ reaction was unchanged and OCB persisted. Direct comparison of OCB pattern before and after NTZ revealed the persistence of individual bands. α4-Integrin expression was highest on plasmablasts (CD19+CD38+CD27+).

Conclusion Our data indicate that NTZ reduces short-lived plasmablasts in the CNS compartment but has little effect on locally persisting long-lived plasma cells.

So they say that there is more protein on plasma blasts, I say I can confirm this by looking at message for the two proteins that make up the target for natalizumab

General Disclaimer: Please note that the opinions expressed here are those of the author and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice. 

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