Abstract Details

Title Differential Loss of KIR4.1 on Oligodendrocytes and Astrocytes in Multiple Sclerosis Lesions

Topic MS and Related Diseases

Presentation(s) S21 - (-)

Poster/Presentation
Number 003

Objective

Background Antibodies against the inward rectifying potassium channel KIR4.1 are found in a subpopulation of MS patients suggesting a role of KIR4.1 as a target of the autoimmune response in MS. Little is known about the expression of KIR4.1 in normal brain tissue and MS lesions.

Design/Methods We analysed the binding of KIR4.1 specific antibodies (KIR4.1-IgG) from MS patients in normal brain tissue, and the expression of KIR4.1 in active, early inactive and late inactive MS subcortical periplaque and demyelinated white matter (DM-WM) lesions.

Results While KIR4.1 was widely expressed in oligodendrocytes and astrocytes in the normal brain, KIR4.1-IgG predominantly bound to homomeric KIR4.1 expressed by oligodendrocytes and perivascular astrocytes. In active lesions, we found a loss of KIR4.1 positive oligodendrocytes and perivascular astrocytes, but an enhanced immunoreactivity of KIR4.1 in reactive astrocytes in the periplaque white matter. Apoptotic KIR4.1 positive glial cells and phagocytes containing KIR4.1 positive degradation products were observed in active DM-WM lesions. Complement activation visualized by C9neo deposition was detected on astrocytes, oligodendrocytes and in phagocytes in active DM-WM in KIR4.1-IgG positive patients. In early inactive DM-WM, we observed a differential loss of astrocytic KIR4.1 but not of GFAP. Conversely, KIR4.1 immunoreactivity was restored on astrocytes in late inactive DM-WM lesions and characteristic of the astrocytic fibre gliosis. In remyelinating lesions, Olig2 positive premyelinating oligodendrocytes also expressed KIR4.1.

Conclusions Overall, these findings are consistent with the idea of a primary immune response against KIR4.1 at least in a subset of MS patients.

Authors/Disclosures
Lucas Schirmer, MD (Medical Faculty Mannheim, Heidelberg University) PRESENTER	No disclosure on file
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Hooman Kamel, MD (Weill Cornell Medical College)	Dr. Kamel has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Kamel has received personal compensation in the range of $50,000-$99,999 for serving as a Endpoint adjudication committee with Boehringer-Ingelheim.
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Bernhard Hemmer, MD (Technische Universität München)	No disclosure on file

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