Immunoglobulin-mediated CNS repair

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Immunoglobulin-mediated CNS repair Arthur E. Warrington, PhD, Allan J. Bieber, PhD, Bogoljub Ciric, PhD, Virginia Van Keulen, MS, Larry R. Pease, PhD, Yoshihiro Mitsunaga, MD, M.Mateo Paz Soldan, MS, Moses Rodriguez, MD Journal of Allergy and Clinical Immunology Volume 108, Issue 4, Pages S121-S125 (October 2001) DOI: 10.1067/mai.2001.118301 Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 1 White matter pathology within the spinal cord of TMEV-infected mice. A, Light photomicrograph of a thoracic level spinal cord section from an SJL/J mouse chronically infected with TMEV. White matter at the periphery stains darker than the lighter central gray matter. Demyelinated lesions are present at the extreme periphery of the dorsal, ventral, and lateral columns. B, Higher magnification light photomicrograph of a chronic demyelinated lesion. A few infiltrating inflammatory cells (black arrow ), signs of active disease, are present along with demyelinated axons. Limited OL remyelination is present. C, An example of ongoing OL remyelination. Multiple macrophages ingesting myelin debris are present amid remyelinated axons. Remyelinated axons are distinguished by relatively thin myelin sheaths in relation to axon diameter. Normally myelinated axons are present in the upper right. Scale bar is 100 μmm in A and 20 μmm in B and C . Journal of Allergy and Clinical Immunology 2001 108, S121-S125DOI: (10.1067/mai.2001.118301) Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 2 Treatment with human antibodies promotes remyelination in spinal cord lesions. Comparison of the percent remyelination measured in chronically TMEV-infected mice following treatment with IVIG (IgG ), polyclonal human IgM, human mAbs 1, 2, 14, 22, and 46, and phosphate buffered saline (PBS ). Human mAbs 14, 22, and 46 bind to human OLs in culture; human mAbs 1 and 2 do not bind. Morphology was performed 5 weeks following intraperitoneal injection of human antibodies. Values represent the mean ± SEM the area of CNS remyelination as a percent of the total area of white matter pathology. Statistical analysis comparing mice treated with human antibodies to mice treated with PBS was performed using one way ANOVA and Student t test. Such analysis revealed: * P < .05; + P < .01; and ‡ P < .001. Comparison of mice treated with polyclonal human IgG to other treatments revealed polyclonal human IgM P = .05 and sHIgM 46 P < .05. All other comparisons were not statistically significant. There was no statistical difference between the CNS-type remyelination between polyclonal human IgM, sHIgM 22, and sHIgM 46. There was no statistical difference in the total area of white matter pathology or the area of myelin pathology in the various treatment groups. Number of mice in each treatment group was IgG (10), IgM (14), human mAb 1 (4), human mAb 2 (4), human mAb 14 (7), human mAb 22 (8), human mAb 46 (5), and PBS (7). For a detailed description of the methods for quantitation of white matter area, myelin pathology, and remyelination, see reference 15. Journal of Allergy and Clinical Immunology 2001 108, S121-S125DOI: (10.1067/mai.2001.118301) Copyright © 2001 Mosby, Inc. Terms and Conditions