ABSTRACT
OBJECTIVE: We previously showed that serum IgG repertoires distinguished multiple sclerosis (MS) patients from healthy subjects and from patients with other inflammatory neurological diseases (OIND). We questioned whether the serum IgG repertoire of patients presenting a clinically isolated syndrome (CIS) could predict MS. METHODS: The global IgG immune responses against brain antigens in sera from 50 CIS patients were evaluated by immunoblotting. The IgG reactivities were compared with those from MS sera (n = 82), healthy sera (n = 27), and sera from OIND (n = 42). A linear discriminant analysis (LDA) defined a score for each individual. RESULTS: About 78% of scores obtained from CIS patients were located in the "MS area." During the follow-up (3.5 +/- 1.3 years), 28 patients fulfilled the McDonald criteria for MS, 15 patients remained CIS, and 7 patients developed OIND. Among the patients with an LDA score in the "MS area," 61.5% converted to MS. DISCUSSION: Our results suggest that a pathological distortion of the self-reactive IgG repertoire occurs early so that immunomodulating treatment should be started as early as possible; they also highlight the early involvement of B cells in the physiopathological process in MS.
Subject(s)
B-Lymphocytes/immunology , Biomarkers/blood , Immunoglobulin G/blood , Multiple Sclerosis/epidemiology , Multiple Sclerosis/immunology , Antibody Specificity , Brain/immunology , Female , Humans , Male , Nerve Tissue Proteins/immunology , Predictive Value of Tests , Risk Factors , Seroepidemiologic StudiesABSTRACT
Glutamine synthetase (GS)-encoding genes in Lupinus luteus constitute a small family of genes showing different expression patterns [Boron et al., Acta Biochim. Polon. 36 (1989) 295-301]. One member of this family, the LlNGS1 gene, is strongly induced in root nodules close to the onset of nitrogen fixation and is referred to as a nodule-enhanced GS gene. We present here the structure of the nodule-enhanced LlNGS1 gene, the first gene of this class which has been sequenced. LlNGS1 is composed of twelve exons and shows structural similarity to the GS gene from Medicago sativa, indicating structure conservation of GS genes in legumes. Comparison of protein coding regions, as well as 5'-untranslated regions derived from LlNGS1 and a Lupinus angustifolius pGS5 GS cDNA clone [Grant et al., Plant Mol. Biol. 13 (1989) 481-490], revealed a high degree of shared identity between both genes, indicating that they are orthologous. The sequence of the LlNGS1 5'-flanking region (2.3 kb) contains several elements implicated in regulation of nodulin genes, as well as other characteristic DNA motifs. RNA blot hybridization analysis carried out using a probe corresponding to the LlNGS1 3'-untranslated region revealed that this gene is also transcribed in leaves, but at a barely detectable level.
Subject(s)
Fabaceae/enzymology , Glutamate-Ammonia Ligase/genetics , Membrane Proteins , Plants, Medicinal , Amino Acid Sequence , Base Sequence , Cloning, Molecular , DNA, Complementary , Fabaceae/genetics , Gene Expression , Genes, Plant , Molecular Sequence Data , Nitrogen Fixation/genetics , Plant Proteins/genetics , Sequence Homology, Nucleic Acid , Transcription, GeneticABSTRACT
Two glutamine synthetase (GS) cDNA clones from L. luteus were identified and characterized. The nucleotide sequence analysis proved that they represent highly homologous but distinct mRNA species. Northern blot hybridization revealed that pc LINGS encodes the nodule-specific subunit of the GS while pcLIGS1 represents the nonspecific one present in nodule tissue as well as in uninfected roots.
