American Academy of Neurology Update - Wednesday, April 30th

The Tisch MS research center presented several more posters at the Philadelphia AAN meeting, including:

Cerebrospinal Fluid Mononuclear Phagocytes Are Decreased In Number and Express Less IL-10 In Multiple Sclerosis Compared To Values Seen With Normal Controls

Shivani Agarwal, Irene Jarchum, Ying Liu, Saud A. Sadiq

Summary:

We analyzed the cellular composition of the CSF of 21 MS patients and when compared to healthy controls the MS patients’ CSF had a significantly lower percentage of mononuclear phagocytes (monocytes and microglia). An analysis of their gene expression also revealed that the mononuclear phagocytes expressed lower levels of IL-10 (an immune modulating cytokine). The role of mononuclear phagocytes in MS has previously been unclear, and our findings indicate that they may be an important regulatory cell type. 

Grey matter expression of fetuin-A correlates with cortical demyelination in Multiple Sclerosis

Mark A. Landy, Ying Liu, Violaine K. Harris, Saud A. Sadiq

Summary:

Fetuin-A in the cerebrospinal fluid has been previously identified as a biomarker for active disease in MS. In this study, we investigated fetuin as a possible biomarker for cortical lesions, which cannot be accurately identified by MRI. We completed the experiment by staining sections of post-mortem brain tissue to visualize the expression pattern of fetuin within grey matter lesions, and found that those affecting the surface layers of the cortex tend to express the protein more than lesions deeper within the brain. Because the role of fetuin-A as a biomarker is still relatively new to the field of MS, most of the audience was curious about the protein itself and its possible role in the disease, and they were interested and surprised to see how much work our lab has already done in that regard.

Protein Expression Profiles in Benign and Aggressive Multiple Sclerosis

Ying Liu, Marwan Alahiri, Shivani Agarwal, and Saud Sadiq

Summary:

To better understand the basis of disease severity in MS, we compared the protein profiles in CSF of patients with benign MS versus aggressive MS. Haptoglobin was significantly higher in AMS, and expressed by reactive astrocytes and macrophages in MS lesions. These findings may be indicative of aggressive disease and its association with reactive astrogliosis may drive sclerosis formation and disability.

Fetuin-A, a cerebrospinal fluid (CSF) biomarker of multiple sclerosis (MS) disease activity, promotes immune cell infiltration into the CNS 

Lena H. Bell, Violaine K. Harris, Mark A. Landy, Kristi M. Clark, Saud A. Sadiq

Summary:

Fetuin-A is a protein that we recently identified as a cerebrospinal fluid (CSF) biomarker of disease activity in MS. We sought to understand the role of Fetuin-A in MS using the experimental autoimmune encephalomyelitis (EAE) MS animal model. We analyzed differences between wild-type and Fetuin-A-deficient mice in both the classical and adoptive transfer models of EAE. We found that Fetuin-A-deficient mice were completely resistant to developing EAE after receiving spleen cells from wild-type EAE mice. These findings suggest that Fetuin-A plays a direct role in the activation and trafficking of immune cells into the CNS during EAE. The audience was very interested in our research because Fetuin-A is not a well-known protein in regard to MS.  

B Cell Subsets in the Cerebrospinal Fluid of Multiple Sclerosis Patients

Christopher Sears, Jerry Lin, and Saud A. Sadiq

Summary:

This project aimed to determine the differences in the cerebrospinal fluid profiles of mature B cells in MS clinical subtypes. Significant differences were found in the percentages of certain B cell subtypes between SPMS and PPMS patients. These findings will help direct future research on B cells in MS.

The Specificity of CSF B Cell Reactivity in HTLV-1 Associated Myelopathy

Jerry Lin, Alexandra Berman, Christopher Sears, Saud Sadiq

Summary:

This project successfully established an experimental technique that we will use in our efforts to find the cause of MS. Due to our results, we now know that we can use patient cerebrospinal fluid to create functional recombinant antibodies from B cells, and test their reactivity to potential antigens.