11 research outputs found
Characteristics of the cohort.
a<p>IFNβ preparation could be assigned to 358 of the 364 NAb positive patients, while the type of preparation used was unspecified for 6 NAb positive patients.</p><p>Abbreviations: IQRâ=âinterquartile range, i.m.â=âintramuscular, s.c.â=âsubcutaneous, TRU/mlâ=âtenfold reduction units per milliliter, IFNβâ=âinterferon beta, NAbâ=âneutralizing antibodies</p
HLA association to development of NAbs and biologically relevant titers.
a<p>Major HLA alleles (>5% allele frequency) nominally associated or previously reported to be associated with development of NAbs and biologically relevant titers are presented. All HLA alleles can be found in <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090479#pone.0090479.s002" target="_blank">Table S2</a></b> and <b>S3</b>.</p>b<p>nominal <i>P</i>-values assessed by Chi square test,</p>c<p>Bonferroni corrected <i>P</i>-values (76 allele groups tested).</p><p>Abbreviations: BRTâ=âbiologically relevant titers, C.I.â=âconfidence interval, NAbâ=âneutralizing antibodies, ORâ=âodds ratio.</p
Carrier frequency and absolute risk for HLA allele groups associated to NAb development and biologically relevant titers<sup>a</sup>.
a<p>All HLA allele groups can be found in <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090479#pone.0090479.s005" target="_blank">Table S5</a></b>.</p>b<p>Treatment only is the frequency of NAb development and biologically relevant titers for each treatment regardless of genotype.</p>c<p>The absolute risk for each HLA allele group is calculated with Bayes' theorem and assessed based on frequency and impact on NAb development.</p>d<p>Nominal <i>P</i>-values from Fishers exact test.</p>e<p>Bonferroni corrected <i>P</i>-values (allele groups tested: 12 tests for i.m. IFNβ-1a, 19 tests for IFNβ-1b, 38 for s.c. IFNβ-1a).</p><p>Abbreviations: ARâ=âabsolute risk, C.I.â=âconfidence interval, ORâ=âodds ratio, IFNβâ=âinterferon beta, n/aâ=ânot applicable, NAbâ=âneutralizing antibodies.</p
Independence of the protective class I haplotype from <i>DRB1</i><i>*</i><i>15</i> demonstrated in two ways.
<p>Counts are made in number of chromosomes carrying the haplotypes estimated in UNPHASED within the cohort. âHaplotype +â was all chromosomes with both <i>A*02</i>, <i>C*05</i> and <i>B*12</i> disregarding the <i>DRB1</i> locus, âHaplotype ââwere all chromosomes that did not have all three allele groups (<i>A*02</i>, <i>C*05</i> and <i>B*12</i>) at once, still disregarding DRB1. â<i>DRB1*15</i>+â was all chromosomes carrying <i>DRB1*15</i> disregarding class I allele groups and vice versa for the â<i>DRB1*15</i> ââ.</p>*<p>) Odds ratio for the class I haplotype within <i>DRB1*15</i> positive and negative haplotypes respectively.</p>**<p>) Odds ratio for <i>DRB1*15</i> within the class I haplotype and class I haplotype negative respectively. Note: Class I haplotype negative chromosomes can carry parts of the protective haplotype (i.e. <i>A*02</i> but in that case not <i>C*05</i> and/or <i>B*12</i>).</p
Risk carried by each of the nominally significant allele groups in the logistic regression model for carriage coded <i>DRB1*15</i> negative and positive strata.
<p>Country of origin and gender were included in the models as covariates. <i>DRB1*15</i> was coded as dose (0,1,2), all other allele groups were coded for carriage (0,1).</p
Interaction analysis showing evidence of interaction between <i>DRB1</i><i>*</i><i>15</i> and other allele groups influencing the risk of MS.
*<p>â=ârisk is coded as absence of this allele group since it is nominally protective.</p>#<p>â=âModel has significantly better fit than one with only the two variables by themselves (no interaction term).</p
Odds ratios for haplotypes carrying any combination of <i>A*02</i>, <i>C*05</i> and <i>B*12</i>.
<p>Odds ratios for haplotypes containing one or two of the allele groups of the protective class I haplotype compared to the full protective class I haplotype disregarding the <i>DRB1</i> locus. Chromosomes carrying both <i>A*02</i> and <i>B*12</i> was the only combination within this setting that had the same risk as the protective haplotype, the risk of MS was significantly higher for all other combinations.â+ââ=âChromosomes carrying the allele group specified to the left, âHâââ=âchromosomes carrying other allele group than the one specified to the left (i.e. not the complete protective haplotype). ORâ=âodds ratio with 95% confidence interval, nominal p-value and Bonferroni corrected p-values derived from chi square test with full protective haplotype as reference.</p
Odds ratios for chromosomes carrying only the protective haplotype or <i>DRB1*15</i> or both.
<p>Chromosomes carrying both <i>DRB1*15</i> and the protective class I haplotype do not differ in risk of MS from chromosomes not carrying either of them (reference). <i>DRB1*15</i> carriage increase risk of MS significantly and carriage of the class I haplotype significantly decrease risk of MS. Counts are measured in chromosomes and only individuals with estimated haplotypes with a probability of more than 80% were included. â+ââ=âChromosomes positive for the protective haplotype or <i>DRB1*15</i>, âââ and âHâââ=âchromosomes negative for <i>DRB1*15</i> or the protective haplotype. ORâ=âodds ratio with 95% confidence interval, nominal p-value and Bonferroni corrected p-values derived from chi square test with doubly negative chromosomes as reference.</p
Major allele groups and their frequencies in the Scandinavian sample set.
<p>Some individuals were not genotyped deeply enough to distinguish allele groups. Therefore, major allele groups containing several allele groups were created when needed.</p>â <p>Figure in parenthesis is the percentage of this allele group in this major allele group.</p
Risks carried by each of the nominally significant allele groups from the final logistic regression analyses.
<p>FDRâ=âFalse discovery rate, performed in R, based on the paper <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036779#pone.0036779-Rothman1" target="_blank">[37]</a>.</p