Figures index

From

Relationship Between Genotype and Disease Phenotype for Gluten-Related Disorders

Michael F. Roberts, Nadine Grzeskowiak, Stephen E. Bricher

International Journal of Celiac Disease. 2024, 12(1), 33-40 doi:10.12691/ijcd-12-1-7
  • Figure 1. Haplotype-phenotype relation for T Cell activation. Three peoples’ HLA diploid haplotypes are shown. At the left of each is the DQ haplotype of maternal and paternal chromosome 6, showing alleles for A1 and B1 genes (as shown, these genes are adjacent to each other on the chromosome). A dendritic cell (square outline), expresses the  protein pairs possible for each person (black and open rectangles match black and open portions of chromosome 6 at left). At the right of each is the predicted number of T cell activation units likely for each person, based on the idea that A1*05 B1*02 presents epitope strongly and activates T cells. Panel A: A1*05 B1*02 homozygote: all four  heterodimers bind and present epitope and have score of 1. Panel B: A1*02 B1*02 presents with half the strength of A1*05 B1*02; the A1*05 B1*03 does not present epitope but allows the trans formation of  protein pair. Panel C: A1*01*B1*05 or A1*01 B1*06 do not present epitope at all and have score of 0. Thus, the DQ2.5/DQ2.5 homozygote (A) is predicted to be the strongest CD genotype, the DQ5/DQ6 genotype (C) is not predicted to be a CD genotype, and the DQ2.2/DQ7.5 (B) is predicted to be intermediate
  • Figure 2. Distribution of the age at biopsy diagnosis for all subjects. Panel A: Percentage of subjects diagnosed in each 10-year age period. The curve is a best-fit quadratic function suggesting peak age of diagnosis is about 40 years of age. Panel B: cumulative proportions over all ages, suggesting that disease prevalence cannot be accurately estimated until people of almost all ages have been included
  • Figure 3. Relation between antibody titers (times reference) on the vertical axis and DQ haplotype binding scores () on the horizontal axis. The circles represent median ± SE of tTGA/EMA for each haplotype binding score. Thus, subjects with haplotype binding score of 4 are DQ2.5/2.5 homozygotes while subjects with score of 0 are DQX.x homozygotes lacking any CD-associated haplotypes. The slope of the linear regression is significantly different from zero (p<0.05) and suggests that antibody production is proportional to allele dose of the HLA DQ A1 and B1 genes
  • Figure 4. Relation of symptoms per subject (intestinal+skin+neural) to their haplotype binding score. The circles represent means ± SE for the number of reported symptoms. The slope of the linear regression is not significantly different from zero, indicating that symptom frequency is not associated with haplotype binding score. Note in particular that those with zero haplotype score also have the same number of symptoms as those with high binding scores