RANTES: a genetic risk marker for multiple sclerosis

2004 ◽  
Vol 10 (5) ◽  
pp. 536-539 ◽  
Author(s):  
Radhika Gade-Andavolu ◽  
David E Comings ◽  
James MacMurray ◽  
Ravi K Vuthoori ◽  
Wallace W Tourtellotte ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Risk ◽  
Promoter Region ◽  
Potential Role ◽  
Primary Diagnosis ◽  
Brain Lesions ◽  
Postmortem Brain ◽  
Proximal Promoter ◽  
Promoter Polymorphisms ◽  
Functional Polymorphisms

Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a beta-chemokine and has been detected in brain lesions of multiple sclerosis (MS) patients. Considering its potential role in MS, we screened two functional polymorphisms in the proximal promoter region of the RANTES in MS patients versus controls. Methods: We examined 140 postmortem brain samples from subjects with a primary diagnosis of MS, and peripheral blood samples from 216 control subjects. The RANTES-28C/G and -403G/A promoter polymorphisms were examined. All subjects were non-Hispanic Caucasians. Results: MS cases differed from controls showing a significant association with the 403G/A polymorphism (odds ratio, 2.359, [1.465-3.799]; P-0.0001), but not the -28C/G (P-NS) polymorphism. There was a significant association of the -28G allele with both early onset (P-0.031) and longer survival (P-0.006). Conclusion: There is a significant but complex association of the RANTES gene with MS.

Unbiased examination of genome-wide human endogenous retrovirus transcripts in MS brain lesions

2021 ◽  
pp. 135245852098726
Author(s):  
Maria L Elkjaer ◽  
Tobias Frisch ◽  
Arianna Tonazzolli ◽  
Richard Röttger ◽  
Richard Reynolds ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Potential Role ◽  
Brain Lesion ◽  
Endogenous Retrovirus ◽  
Brain Lesions ◽  
Human Endogenous Retrovirus ◽  
High Quality ◽  
Genome Wide ◽  
And Control ◽  
Herv Expression

Background: Human endogenous retrovirus (HERV) expression in multiple sclerosis (MS) brain lesions may contribute to chronic inflammation, but expression of genome-wide HERVs in different MS lesions is unknown. Objective: We examined the HERV expression landscape in different MS lesions compared to control brains. Methods: Transcripts from 71 MS brain samples and 25 control WM were obtained by next-generation RNA sequencing and mapped against HERV transcripts across the human genome. Differential expression of mapped HERV-W and HERV-H reads between MS lesion types and controls was analysed. Results: Out of 6.38 billion high-quality paired end reads, 174 million reads (2.73%) mapped to HERV transcripts. There was no difference in HERVs expression level between MS and control brains, but HERV-W transcripts were significantly reduced in chronic active lesions. Of the four HERV-W transcripts exclusively present in MS, ERV3633503 located on chromosome 7q21.13 close to the MS genetic risk locus had the highest number of reads. In the HERV-H family, 75% of transcripts located to nearby 7q21-22 were overrepresented in MS, and ERV3643914 was expressed more than 16 times in MS compared to control brains. Conclusion: Novel HERV-W and HERV-H transcripts located at chromosome 7 regions were uniquely expressed in MS lesions, indicating their potential role in brain lesion evolution.

scholarly journals Is Chlamydia pneumoniae Present in Brain Lesions of Patients with Multiple Sclerosis?

2000 ◽  
Vol 38 (11) ◽  
pp. 4274-4276 ◽  
Author(s):  
Margaret R. Hammerschlag ◽  
Zheng Ke ◽  
Fengmin Lu ◽  
Patricia Roblin ◽  
Jens Boman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Chlamydia Pneumoniae ◽  
Pcr Amplification ◽  
Initial Study ◽  
Brain Lesions ◽  
Postmortem Brain ◽  
Brain Tissues

We investigated the presence of Chlamydia pneumoniae in 81 normal and pathological specimens obtained from postmortem brain tissues of patients with multiple sclerosis and with other neurological or nonneurological diseases. The assays used included PCR amplification of all DNA samples in the initial study. Culture and a second PCR amplification of the organism in a subset of 19 brain specimens were also performed in two separate laboratories. All results were negative. Thus, this study on a large number of brain tissues suggests thatC. pneumoniae is not involved in inflammatory demyelination.

scholarly journals CSF proteome in multiple sclerosis subtypes related to brain lesion transcriptomes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria L. Elkjaer ◽  
Arkadiusz Nawrocki ◽  
Tim Kacprowski ◽  
Pernille Lassen ◽  
Anja Hviid Simonsen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Protein Phosphatase ◽  
Brain Lesion ◽  
Brain Lesions ◽  
Cns Diseases ◽  
Secondary Progressive ◽  
Apolipoprotein A ◽  
Proteomic Approach ◽  
Apolipoprotein C ◽  
Altered Proteins

AbstractTo identify markers in the CSF of multiple sclerosis (MS) subtypes, we used a two-step proteomic approach: (i) Discovery proteomics compared 169 pooled CSF from MS subtypes and inflammatory/degenerative CNS diseases (NMO spectrum and Alzheimer disease) and healthy controls. (ii) Next, 299 proteins selected by comprehensive statistics were quantified in 170 individual CSF samples. (iii) Genes of the identified proteins were also screened among transcripts in 73 MS brain lesions compared to 25 control brains. F-test based feature selection resulted in 8 proteins differentiating the MS subtypes, and secondary progressive (SP)MS was the most different also from controls. Genes of 7 out these 8 proteins were present in MS brain lesions: GOLM was significantly differentially expressed in active, chronic active, inactive and remyelinating lesions, FRZB in active and chronic active lesions, and SELENBP1 in inactive lesions. Volcano maps of normalized proteins in the different disease groups also indicated the highest amount of altered proteins in SPMS. Apolipoprotein C-I, apolipoprotein A-II, augurin, receptor-type tyrosine-protein phosphatase gamma, and trypsin-1 were upregulated in the CSF of MS subtypes compared to controls. This CSF profile and associated brain lesion spectrum highlight non-inflammatory mechanisms in differentiating CNS diseases and MS subtypes and the uniqueness of SPMS.

scholarly journals Elucidating distinct clinico-radiologic signatures in the borderland between neuromyelitis optica and multiple sclerosis

2021 ◽  
Author(s):  
Maciej Juryńczyk ◽  
Elżbieta Klimiec-Moskal ◽  
Yazhuo Kong ◽  
Samuel Hurley ◽  
Silvia Messina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Unmet Need ◽  
Transverse Myelitis ◽  
Overlap Syndrome ◽  
Brain Lesions ◽  
Central Vein ◽  
Normal Brain ◽  
Group 4 ◽  
Group 2

Abstract Background Separating antibody-negative neuromyelitis optica spectrum disorders (NMOSD) from multiple sclerosis (MS) in borderline cases is extremely challenging due to lack of biomarkers. Elucidating different pathologies within the likely heterogenous antibody-negative NMOSD/MS overlap syndrome is, therefore, a major unmet need which would help avoid disability from inappropriate treatment. Objective In this study we aimed to identify distinct subgroups within the antibody-negative NMOSD/MS overlap syndrome. Methods Twenty-five relapsing antibody-negative patients with NMOSD features underwent a prospective brain and spinal cord MRI. Subgroups were identified by an unsupervised algorithm based on pre-selected NMOSD/MS discriminators. Results Four subgroups were identified. Patients from Group 1 termed “MS-like” (n = 6) often had central vein sign and cortical lesions (83% and 67%, respectively). All patients from Group 2 (“spinal MS-like”, 8) had short-segment myelitis and no MS-like brain lesions. Group 3 (“classic NMO-like”, 6) had high percentage of bilateral optic neuritis and longitudinally extensive transverse myelitis (LETM, 80% and 60%, respectively) and normal brain appearance (100%). Group 4 (“NMO-like with brain involvement”, 5) typically had a history of NMOSD-like brain lesions and LETM. When compared with other groups, Group 4 had significantly decreased fractional anisotropy in non-lesioned tracts (0.46 vs. 0.49, p = 0.003) and decreased thalamus volume (0.84 vs. 0.98, p = 0.04). Conclusions NMOSD/MS cohort contains distinct subgroups likely corresponding to different pathologies and requiring tailored treatment. We propose that non-conventional MRI might help optimise diagnosis in these challenging patients.

scholarly journals Analysis of proteins binding to the proximal promoter region of two rat serine protease inhibitor genes

1992 ◽  
Vol 20 (5) ◽  
pp. 1061-1068 ◽  
Author(s):  
Valerie Rossi ◽  
Jean Francois Rouayrenc ◽  
Laurent Paquereau ◽  
Marie Joseé Vilarem ◽  
Alphonse Le Cam
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Promoter Region ◽  
Serine Protease Inhibitor ◽  
Proximal Promoter ◽  
Proximal Promoter Region ◽  
Inhibitor Genes

scholarly journals NRAMP1 Polymorphism and Viral Factors in Sardinian Multiple Sclerosis Patients

2008 ◽  
Vol 35 (4) ◽  
pp. 491-494 ◽  
Author(s):  
Maria Gazouli ◽  
Leonardo Sechi ◽  
Daniela Paccagnini ◽  
Stefano Sotgiu ◽  
Giannina Arru ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Disease ◽  
Promoter Region ◽  
Viral Infections ◽  
Jc Virus ◽  
Allelic Variation ◽  
Sardinian Population ◽  
Multiple Sclerosis Patients ◽  
Viral Sequences

Background:Multiple sclerosis (MS) is believed to be an autoimmune disease occurring in genetically predisposed individuals after an appropriate environmental exposure such as viral infections. Recent studies suggest a significant association between MS and the functional 5’-(GT)n polymorphism in the promoter region of the NRAMP1 gene. In the present study we aimed to evaluate the contribution of the allelic variation in the NRAMP1 promoter to MS susceptibility and to study the role of viral infection in relation to specific NRAMP1 genotypes, in a Sardinian cohort.Methods:Sixty MS patients and 66 healthy individuals were genotyped, and screened for the presence of Epstein-bar virus (EBV) and JC virus (JCV) sequences.Results:Consistent with previous autoimmune disease studies, allele 3 at the functional 5’(GT)n promoter region repeat polymorphism, was significantly overrepresented among MS patients when compared to controls (p=0.02). The EBV and JCV sequences were detected in 8/60 (13.33%) and in 4/60 (6.66%) of MS patients respectively and in 5/66 (7.57%) and in 0/66 of controls.Conclusion:The allelic variation in the NRAMP1 promoter may contribute to MS susceptibility in the Sardinian population. The viral sequences were not confined to a specific NRAMP1 genotype.

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