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Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS
Luisa M. Villar, … , Alfredo Bootello, José C. Álvarez-Cermeño
Luisa M. Villar, … , Alfredo Bootello, José C. Álvarez-Cermeño
Published January 3, 2005
Citation Information: J Clin Invest. 2005;115(1):187-194. https://doi.org/10.1172/JCI22833.
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Article Immunology

Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS

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Abstract

Oligoclonal IgM bands restricted to cerebrospinal fluid are an unfavorable prognostic marker in MS, the most common demyelinating disease of the CNS. We have attempted to identify the B cell subpopulation responsible for oligoclonal IgM secretion and the specificity of these bands. In addition, we explored the relationship between specificity and disease evolution. Intrathecal B cell subpopulations present in 29 MS patients with oligoclonal IgM bands and 52 without them were analyzed. A considerable increase in CD5+ B lymphocytes was found in patients with oligoclonal IgM bands. These cells mostly secrete IgM antibodies recognizing nonproteic molecules. We also studied whether oligoclonal IgM bands present in cerebrospinal fluid of 53 MS patients were directed against myelin lipids. This was the case in most patients, with phosphatidylcholine being the most frequently recognized lipid. Disease course of 15 patients with oligoclonal IgM against myelin lipids and 33 patients lacking them was followed. Patients with anti-lipid IgM suffered a second relapse earlier, had more relapses, and showed increased disability compared with those without anti-lipid IgM. The presence of intrathecal anti–myelin lipid IgM antibodies is therefore a very accurate predictor of aggressive evolution in MS.

Authors

Luisa M. Villar, María C. Sádaba, Ernesto Roldán, Jaime Masjuan, Pedro González-Porqué, Noelia Villarrubia, Mercedes Espiño, José A. García-Trujillo, Alfredo Bootello, José C. Álvarez-Cermeño

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Figure 1

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Study of B cells in CSF of MS patients with and without OCMBs. (A) Both ...
Study of B cells in CSF of MS patients with and without OCMBs. (A) Both M+ MS and M– MS OCMBs showed a higher percentage of CD19+ cells in CSF when compared with the control group (P < 0.0001). In addition, M+ MS patients show a higher percentage of CD19+ cells when compared with M– MS patients (P = 0.0005). (B) Representative dot plots showing CD19+ cells present in CSF of an M+ MS patient (left), an M– MS patient (center), and a patient from the control group (right). CD19-PerCP-Cy5.5, CD19–peridinin-chlorophyll-protein–Cy-Chrome 5.5.
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