Contributions
Abstract: EP1554
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: The pathogenesis of multiple sclerosis (MS) is thought to involve autoreactive T lymphocytes that have the capacity to invade the central nervous system and promote tissue damage. Programmed cell death (apoptosis) of activated autoreactive T lymphocytes is one of the mechanisms involved in the maintenance of the immunological tolerance. A failure in the deletion of potentially pathogenic cells might lead to a major persistence of these cells in peripheral blood. In the present study, we aimed to explore the role of a large panel of pro- and anti-apoptotic factors by measuring the expression levels in peripheral blood mononuclear cells (PBMC) from MS patients with different clinical forms of the disease.
Methods: The mRNA expression levels of BID, BAK, BAX, BAD, BIM, SMAC, BNIP3, NOXA, PUMA (pro-apoptotic molecules), and BCL-2, BCL-XL, BCL-W, MCL-1, FAIM1, FAIM2, LFG, FLIP, FLIP-L, clAP-1, clAP-2 (anti-apoptotic molecules) were measured by real time PCR in PBMC from 12 healthy controls and 29 untreated MS patients [17 patients with relapsing-remitting MS (RRMS), 12 with primary-progressive MS (PPMS), and 6 RRMS patients during the relapses].
Results: The most differentially expressed gene between healthy controls and RRMS patients corresponded to PUMA (p53 unregulated modulator of apoptosis), and the expression levels for this gene were significantly down-regulated in RRMS compared to controls (p= 0.019). BID (BH3 Interacting Domain Death Agonist) and BAD (BCL2 Associated Agonist of Cell Death) expression levels were significantly down-regulated in PPMS patients as compared to healthy controls (p=0.047 and p=0.024 respectively). BID expression levels were also significantly decreased in PPMS patients compared to RRMS patients (p=0.0094).
Conclusions: These findings support a role for the pro-apoptotic factors PUMA, BID and BAD in the pathogenesis of MS. Western blot studies are currently in progress to investigate whether differences in mRNA expression levels for these genes are also present at the protein level.
Disclosure: S Malhotra, C Matute-Blanch, M Moreno, L Negrotto and E Sarró report no disclosures.
M Tintoré has received compensation for consulting services and speaking from Bayer-Schering, Merk-Serono, Biogen-Idec, Teva, Sanofi-Aventis, and Novartis.
L Negrotto has received travel stipends from Biogen Idec Argentina and TEVA Argentina.
J. Rio has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, Genzyme, and Novartis.
X Montalban has received speaking honoraria and travel expenses for scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer Schering Pharma, Biogen Idec, EMD Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva Phramaceuticals, Almirall and Roche.
M Comabella has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, Genzyme, and Novartis.
Abstract: EP1554
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: The pathogenesis of multiple sclerosis (MS) is thought to involve autoreactive T lymphocytes that have the capacity to invade the central nervous system and promote tissue damage. Programmed cell death (apoptosis) of activated autoreactive T lymphocytes is one of the mechanisms involved in the maintenance of the immunological tolerance. A failure in the deletion of potentially pathogenic cells might lead to a major persistence of these cells in peripheral blood. In the present study, we aimed to explore the role of a large panel of pro- and anti-apoptotic factors by measuring the expression levels in peripheral blood mononuclear cells (PBMC) from MS patients with different clinical forms of the disease.
Methods: The mRNA expression levels of BID, BAK, BAX, BAD, BIM, SMAC, BNIP3, NOXA, PUMA (pro-apoptotic molecules), and BCL-2, BCL-XL, BCL-W, MCL-1, FAIM1, FAIM2, LFG, FLIP, FLIP-L, clAP-1, clAP-2 (anti-apoptotic molecules) were measured by real time PCR in PBMC from 12 healthy controls and 29 untreated MS patients [17 patients with relapsing-remitting MS (RRMS), 12 with primary-progressive MS (PPMS), and 6 RRMS patients during the relapses].
Results: The most differentially expressed gene between healthy controls and RRMS patients corresponded to PUMA (p53 unregulated modulator of apoptosis), and the expression levels for this gene were significantly down-regulated in RRMS compared to controls (p= 0.019). BID (BH3 Interacting Domain Death Agonist) and BAD (BCL2 Associated Agonist of Cell Death) expression levels were significantly down-regulated in PPMS patients as compared to healthy controls (p=0.047 and p=0.024 respectively). BID expression levels were also significantly decreased in PPMS patients compared to RRMS patients (p=0.0094).
Conclusions: These findings support a role for the pro-apoptotic factors PUMA, BID and BAD in the pathogenesis of MS. Western blot studies are currently in progress to investigate whether differences in mRNA expression levels for these genes are also present at the protein level.
Disclosure: S Malhotra, C Matute-Blanch, M Moreno, L Negrotto and E Sarró report no disclosures.
M Tintoré has received compensation for consulting services and speaking from Bayer-Schering, Merk-Serono, Biogen-Idec, Teva, Sanofi-Aventis, and Novartis.
L Negrotto has received travel stipends from Biogen Idec Argentina and TEVA Argentina.
J. Rio has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, Genzyme, and Novartis.
X Montalban has received speaking honoraria and travel expenses for scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer Schering Pharma, Biogen Idec, EMD Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva Phramaceuticals, Almirall and Roche.
M Comabella has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, Genzyme, and Novartis.