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CCR5Delta32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in multiple sclerosis.
J Neuroimmunol. 2005 Dec; 169(1-2):137-43.JN

Abstract

Four distinct patterns of tissue injury have been described in multiple sclerosis (MS) lesions. Infiltrating monocytes in lesions of all patterns co-express CCR1 and CCR5. However, in pattern II lesions, the number of CCR1 cells is decreased, while the number of CCR5 expressing cells is increased in late active versus early active regions. In contrast, CCR1 and CCR5 cells were equal in all regions of pattern III lesions. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support MS pathological heterogeneity. A deletion in CCR5 (CCR5*Delta32), which encodes a truncated, non-functional protein, has been associated with late onset of MS and a favorable prognosis. We studied the association of CCR5*Delta32 with the course and severity of MS in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the MS Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the CCR5*Delta32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or disease course (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the CCR5*Delta32 mutation was not associated with patterns of immunopathology in MS. Despite similar numbers of T-lymphocytes, there were no CCR5+ T-cells nor was CCR5 expressed in the CNS of a homozygous CCR5*Delta32 MS patient, and heterozygous patients had reduced CCR5 expression compared to wild type patients. CCR5*Delta32 has a dose effect on CCR5 expression in the CNS, but is neither necessary for development of MS, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between CCR5*Delta32 mutation and disease severity and age of onset in MS.

Authors+Show Affiliations

Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16182378

Citation

Kantarci, Orhun H., et al. "CCR5Delta32 Polymorphism Effects On CCR5 Expression, Patterns of Immunopathology and Disease Course in Multiple Sclerosis." Journal of Neuroimmunology, vol. 169, no. 1-2, 2005, pp. 137-43.
Kantarci OH, Morales Y, Ziemer PA, et al. CCR5Delta32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in multiple sclerosis. J Neuroimmunol. 2005;169(1-2):137-43.
Kantarci, O. H., Morales, Y., Ziemer, P. A., Hebrink, D. D., Mahad, D. J., Atkinson, E. J., Achenbach, S. J., De Andrade, M., Mack, M., Ransohoff, R. M., Lassmann, H., Bruck, W., Weinshenker, B. G., & Lucchinetti, C. F. (2005). CCR5Delta32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in multiple sclerosis. Journal of Neuroimmunology, 169(1-2), 137-43.
Kantarci OH, et al. CCR5Delta32 Polymorphism Effects On CCR5 Expression, Patterns of Immunopathology and Disease Course in Multiple Sclerosis. J Neuroimmunol. 2005;169(1-2):137-43. PubMed PMID: 16182378.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CCR5Delta32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in multiple sclerosis. AU - Kantarci,Orhun H, AU - Morales,Yazmín, AU - Ziemer,Patricia A, AU - Hebrink,David D, AU - Mahad,Don J, AU - Atkinson,Elizabeth J, AU - Achenbach,Sara J, AU - De Andrade,Mariza, AU - Mack,Matthias, AU - Ransohoff,Richard M, AU - Lassmann,Hans, AU - Bruck,Wolfgang, AU - Weinshenker,Brian G, AU - Lucchinetti,Claudia F, Y1 - 2005/09/22/ PY - 2004/11/29/received PY - 2005/07/13/revised PY - 2005/07/19/accepted PY - 2005/9/27/pubmed PY - 2006/1/26/medline PY - 2005/9/27/entrez SP - 137 EP - 43 JF - Journal of neuroimmunology JO - J. Neuroimmunol. VL - 169 IS - 1-2 N2 - Four distinct patterns of tissue injury have been described in multiple sclerosis (MS) lesions. Infiltrating monocytes in lesions of all patterns co-express CCR1 and CCR5. However, in pattern II lesions, the number of CCR1 cells is decreased, while the number of CCR5 expressing cells is increased in late active versus early active regions. In contrast, CCR1 and CCR5 cells were equal in all regions of pattern III lesions. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support MS pathological heterogeneity. A deletion in CCR5 (CCR5*Delta32), which encodes a truncated, non-functional protein, has been associated with late onset of MS and a favorable prognosis. We studied the association of CCR5*Delta32 with the course and severity of MS in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the MS Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the CCR5*Delta32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or disease course (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the CCR5*Delta32 mutation was not associated with patterns of immunopathology in MS. Despite similar numbers of T-lymphocytes, there were no CCR5+ T-cells nor was CCR5 expressed in the CNS of a homozygous CCR5*Delta32 MS patient, and heterozygous patients had reduced CCR5 expression compared to wild type patients. CCR5*Delta32 has a dose effect on CCR5 expression in the CNS, but is neither necessary for development of MS, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between CCR5*Delta32 mutation and disease severity and age of onset in MS. SN - 0165-5728 UR - https://www.unboundmedicine.com/medline/citation/16182378/CCR5Delta32_polymorphism_effects_on_CCR5_expression_patterns_of_immunopathology_and_disease_course_in_multiple_sclerosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165-5728(05)00318-8 DB - PRIME DP - Unbound Medicine ER -