In vivo gene expression revealed by cDNA arrays: the pattern in relapsing-remitting multiple sclerosis patients compared with normal subjects.
OBJECTIVE
To use DNA arrays to identify differences in gene expression associated with relapsing-remitting (RR) MS.


METHODS
Total RNA was isolated from monocyte depleted peripheral blood mononuclear cells of 15 RR MS patients and 15 age- and sex-matched controls. The RNA was reverse transcribed to radiolabeled cDNA and the resultant cDNA was used to probe a DNA array containing over 4000 named human genes. The binding of radiolabeled cDNA to the probes on the array was measured by phosphorimager.


RESULTS
Of more than 4000 genes tested, only 34 were significantly different in RR-MS patients from controls. Of these, 25 were significantly increased and 9 significantly decreased in the RR MS patients. Twelve of these genes have inflammatory and/or immunological functions that could be relevant to the MS disease process. The potentially relevant genes that were elevated (15% to 28%) were P protein, LCK, cAMP responsive element modulator, IL-7 receptor, matrix metalloproteinase-19, M130 antigen, and peptidyl-prolyl isomerase. Those that were significantly decreased (15% to 35%) were SAS transmembrane 4 superfamily protein, STRL22 (C-C chemokine receptor 6), AFX protein, DNA fragmentation factor-45 and immunoglobulin gamma 3 (Gm marker).


CONCLUSIONS
The RR-MS disease effect was relatively restricted and most of the mRNAs tested were not different from the normal controls. However, there were significant differences identified in the expression of a subset of mRNAs, including 13 with inflammatory/immune functions that could be relevant to MS. The systematic use of DNA arrays can provide insight into the dynamic cellular pathways involved in MS pathogenesis and its phenotypic heterogeneity.
Ramanathan
M
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Department of Pharmaceutics, 543 Cooke Hall, State University of New York at Buffalo, 14260-1200, Buffalo, NY, USA. murali@acsu.buffalo.edu
Weinstock-Guttman
B
B
Nguyen
L T
LT
Badgett
D
D
Miller
C
C
Patrick
K
K
Brownscheidle
C
C
Jacobs
L
L
D000328:Adult; D000373:Agglutinins / Q000235:genetics; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins; D051786:Cyclic AMP Response Element Modulator; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors; D015870:Gene Expression / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D008297:Male; D053505:Matrix Metalloproteinases, Secreted; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D008666:Metalloendopeptidases / Q000235:genetics; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D019696:Peptidylprolyl Isomerase / Q000235:genetics; D011506:Proteins / Q000235:genetics; D054399:Receptors, CCR6; D011956:Receptors, Cell Surface / Q000235:genetics; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000235:genetics; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics; D000098902:CD163 Antigen
D000373:Agglutinins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051017:Apoptosis Regulatory Proteins; C106311:CCR6 protein, human; D000098902:CD163 Antigen; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C108803:FOXO4 protein, human; D051858:Forkhead Transcription Factors; D006023:Glycoproteins; D007074:Immunoglobulin G; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; D011506:Proteins; D054399:Receptors, CCR6; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D020395:Receptors, Interleukin-7; D012097:Repressor Proteins; D014157:Transcription Factors; C109664:caspase-activated DNase inhibitor; C057612:sialic acid specific agglutinin protein, rat; D051786:Cyclic AMP Response Element Modulator; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C108362:matrix metalloproteinase 19; D019696:Peptidylprolyl Isomerase