title: Polymorphic markers in MHC class II/III region: a study on Italian patients with myasthenia gravis.
abstract: With an Italian case series of 81 Italian patients and 130 controls, we analysed associations between myasthenia gravis (MG) and genetic polymorphisms in the MHC class II/III region. Increases in the frequency of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype, which is likely part of the 8.1 ancestral haplotype, were maximal in females with early onset (EO) MG vs. controls [p<0.05, relative risk (RR)=9.9]. These patients showed neither a significantly high frequency of thymic hyperplasia, nor high levels of serum anti-acethylcholine receptor antibodies. The DRB1*03 allele was absent in patients with thymoma; however, in comparison with controls, occurrence of this marker was frequent in MG patients (p<0.005; RR=6.2), more frequent in females (p<0.005; RR=7.8) and most frequent in EOMG female patients (p<0.005; RR=15.1). Analysis of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype and its recombinants showed that the MHC region between C4 and TNF might contain genes that influence susceptibility to MG in females. Polymorphic markers within the supratype, e.g. TNF-B*1 and C4A*Q0, might contribute to pathogenetically significant abnormalities in immune responses in a subset of female MG patients. The combined effect of other intervening genes cannot be excluded.
authors.affiliation: Laboratory of Neuroimmunology, IRCCS, Foundation Neurological Institute C. Mondino, University of Pavia, via Palestro 3, 27100, Pavia, Italy. diego.franciotta@mondino.it
authors.forename: D
authors.initials: D
authors.lastname: Franciotta
authors.forename: M
authors.initials: M
authors.lastname: Cuccia
authors.forename: E
authors.initials: E
authors.lastname: Dondi
authors.forename: G
authors.initials: G
authors.lastname: Piccolo
authors.forename: V
authors.initials: V
authors.lastname: Cosi
mesh_terms: D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D015934:Complement C4a / Q000235:genetics; D015935:Complement C4b / Q000235:genetics; D011415:Complement Factor B / Q000235:genetics; D004252:DNA Mutational Analysis; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005802:Genes, MHC Class II / Q000276:immunology*; D005819:Genetic Markers / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007558:Italy; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D005819:Genetic Markers; D008233:Lymphotoxin-alpha; D015934:Complement C4a; D015935:Complement C4b; C052380:endodeoxyribonuclease NcoI; D015252:Deoxyribonucleases, Type II Site-Specific; D011415:Complement Factor B