Biomarkers //

B cell Biomarker for MG

 

The anti-AChR antibody levels fail to correlate with MG disease severity. Also around 10% of MG patients have no detectable anti-AChR or MuSK or LRP4 antibodies (seronegative). Therefore, early detection of AChR or MuSK antibody producing B cells in the circulation could serve as biomarker that will improve patient management with immunosuppressive therapy and the ability to predict relapses. Also, these biomarkers could identify previously categorized sero-negative patients with AChR or MuSK autoimmune MG.

We are developing biomarkers for MG by using fluorophore conjugated to AChR and MuSK as a probe for identifying potentially pathogenic peripheral blood AChR and MuSK-specific B cells.

When fully developed, this technology will significantly facilitate “real time” disease monitoring, even in early disease, diagnosing seronegative MG, to predict severity/crisis, response to treatment, and relapse.

Hypothetical fluorophore AChR or MuSK conjugate binding to BCR

 



Significantly increased numbers of AChR binding B cells, CD21+ and IgG+ cells have been observed in MG patients compared to healthy controls *.
 

*Yin W, Allman W, Ouyang S, Li Y, Li J, Christadoss P, Yang H. The increased expression of CD21 on AChR-specified B cells in patients with myasthenia gravis. J.Neuroimmunol, 2013; 256:49-54. PMID: 23266128.  

 

Possible use of fluorophore-AChR or MuSK conjugate kit1

in flowcytometry:

 

  1. Test the frequency of AChR- or MuSK- binding B cells in peripheral blood2. That is measuring number of B cells potentially binding to fluorochrome-AChR or MuSK on the B cell receptor (BCR-surface immunoglobulin) in patients with MG and in animals with experimental autoimmune MG (EAMG).
     

  2. Test the frequency of AChR- or MuSK- binding B cells with other cell markers in the peripheral blood and thymus of patients with MG and animals with EAMG3.
     

  3. Test the frequency of AChR- or MuSK- binding B cells in seronegative MG.
     

  4. Test the frequency of AChR- or MuSK- binding B cells with other cell markers in patients with MG before and following immunosuppressive therapy including B cell depletion therapy with rituximab.
     

  5. Purify AChR- or MuSK- binding B cells with specific cell markers to perform detailed functional studies and genetic analysis in MG and EAMG. 
     

  6. Track AChR- or MuSK binding cells in EAMG in vivo.
     

 

1For research use only

 

2Possible binding to other cells

3Allman W, Saini SS, Tuzun E., Christadoss P. Characterization of peripheral blood acetylcholine receptor binding B cells in experimental myasthenia gravis. Cellular Immunology 2011; 271:292-298.

Related references:

1.   Allman W, Saini SS, Tuzun E., Christadoss P. Characterization of peripheral blood acetylcholine receptor binding B cells in experimental myasthenia gravis. Cellular Immunology 2011; 271:292-298. PMID: 21861992  View PDF
 

2.   Yin W, Allman W, Ouyang S, Li Y, Li J, Christadoss P, Yang H. The increased expression of CD21 on AchR specified B cells in patients with myasthenia gravis. J Neuroimmunol, 2013; 256:49-54. PMID: 23266128  View PDF

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