Expression of the inhibitor of apoptosis protein family in multiple sclerosis reveals a potential immunomodulatory role during autoimmune mediated demyelination

A failure of autoreactive T cells to undergo apoptosis may contribute to the pathogenesis of multiple sclerosis (MS). The role of the inhibitor of apoptosis (IAP) family of anti-apoptotic proteins such as X-linked IAP (XIAP), human inhibitor of apoptosis-1 (HIAP-1), human inhibitor of apoptosis-2 (H...

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Veröffentlicht in:Multiple sclerosis 2008-06, Vol.14 (5), p.577-594
Hauptverfasser: Hebb, ALO, Moore, CS, Bhan, V, Campbell, T, Fisk, JD, Robertson, HA, Thorne, M, Lacasse, E, Holcik, M, Gillard, J, Crocker, SJ, Robertson, GS
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container_end_page 594
container_issue 5
container_start_page 577
container_title Multiple sclerosis
container_volume 14
creator Hebb, ALO
Moore, CS
Bhan, V
Campbell, T
Fisk, JD
Robertson, HA
Thorne, M
Lacasse, E
Holcik, M
Gillard, J
Crocker, SJ
Robertson, GS
description A failure of autoreactive T cells to undergo apoptosis may contribute to the pathogenesis of multiple sclerosis (MS). The role of the inhibitor of apoptosis (IAP) family of anti-apoptotic proteins such as X-linked IAP (XIAP), human inhibitor of apoptosis-1 (HIAP-1), human inhibitor of apoptosis-2 (HIAP-2), neuronal apoptosis inhibitory protein (NAIP) and Survivin in relapsing–remitting, secondary-progressive, primary-progressive or benign forms of MS is unclear. We report here that expression of the IAP family of genes in peripheral blood samples and brain tissues from MS cases support a role for differential regulation of these potent anti-apoptotic proteins in the pathology of MS. XIAP mRNA and protein levels were elevated in peripheral blood mononuclear cells from patients with active disease relative to normal subjects. In patients with active MS, HIAP-1 and HIAP-2 mRNA levels were elevated in resting T cells while NAIP mRNA was increased in whole blood. In post-mortem MS brain tissue, XIAP and HIAP-1 in myelin lesions were co-localized with microglia and T cells, respectively. Only in primary-progressive patients was Survivin expression elevated suggestive of a distinct pathological basis for this subtype of MS. Taken together, these results suggest that patterns of inhibitor of apoptosis expression in immune cells may have value in distinguishing between MS subtypes and offer insight into the mechanisms responsible for their distinct clinical courses.
doi_str_mv 10.1177/1352458507087468
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Prion diseases</subject><subject>Demyelinating Diseases - genetics</subject><subject>Demyelinating Diseases - immunology</subject><subject>Demyelinating Diseases - pathology</subject><subject>Female</subject><subject>Gene Expression - immunology</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>Immunologic Factors - genetics</subject><subject>Immunologic Factors - immunology</subject><subject>Inhibitor of Apoptosis Proteins - genetics</subject><subject>Inhibitor of Apoptosis Proteins - immunology</subject><subject>Inhibitor of Apoptosis Proteins - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microglia - immunology</subject><subject>Microtubule-Associated Proteins - genetics</subject><subject>Microtubule-Associated Proteins - immunology</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Middle Aged</subject><subject>Multiple Sclerosis - genetics</subject><subject>Multiple Sclerosis - immunology</subject><subject>Multiple Sclerosis - pathology</subject><subject>Multiple sclerosis and variants. 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subjects Adult
Aged
Autoimmunity - genetics
Autoimmunity - immunology
Baculoviral IAP Repeat-Containing 3 Protein
Biological and medical sciences
Blotting, Western
Brain - pathology
Brain - physiology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Demyelinating Diseases - genetics
Demyelinating Diseases - immunology
Demyelinating Diseases - pathology
Female
Gene Expression - immunology
Gene Expression Profiling
Humans
Immunologic Factors - genetics
Immunologic Factors - immunology
Inhibitor of Apoptosis Proteins - genetics
Inhibitor of Apoptosis Proteins - immunology
Inhibitor of Apoptosis Proteins - metabolism
Male
Medical sciences
Microglia - immunology
Microtubule-Associated Proteins - genetics
Microtubule-Associated Proteins - immunology
Microtubule-Associated Proteins - metabolism
Middle Aged
Multiple Sclerosis - genetics
Multiple Sclerosis - immunology
Multiple Sclerosis - pathology
Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis
Neoplasm Proteins - genetics
Neoplasm Proteins - immunology
Neoplasm Proteins - metabolism
Neurology
Neuronal Apoptosis-Inhibitory Protein - genetics
Neuronal Apoptosis-Inhibitory Protein - immunology
Neuronal Apoptosis-Inhibitory Protein - metabolism
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Ubiquitin-Protein Ligases
X-Linked Inhibitor of Apoptosis Protein - genetics
X-Linked Inhibitor of Apoptosis Protein - immunology
X-Linked Inhibitor of Apoptosis Protein - metabolism
title Expression of the inhibitor of apoptosis protein family in multiple sclerosis reveals a potential immunomodulatory role during autoimmune mediated demyelination
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