Figure 3.
Investigation of other mTOR effectors. (A) Simplified diagram of 3 key effectors of mTORC1. (B) Stained p4EBP1 area proportion in different lymph node regions for the first cohort of iMCD-TAFRO patients compared with 2 control groups: reactive and sentinel lymph nodes. The stained area proportion at the interfollicular space was significantly higher than the reactive and sentinel lymph nodes (P = .0034 and .0013, respectively). (C) Comparison of p70S6K stained area proportions for iMCD (n = 6) vs reactive lymph nodes. There was a nonsignificant elevation for iMCD across the follicle, germinal center, and the interfollicular spaces (P = .17 for all 3 comparisons). (D) Effect size comparison among the 3 mTORC1 effectors. Hedges’ g, an effect size utilizing the mean difference standardized by the deviation, was calculated for the iMCD-TAFRO to reactive lymph node comparison for the 3 stains in the interfollicular space. The 3 results were combined by random effects (RE) model, as we are testing effects related to mTOR activation. Synthesis by RE model yielded a combined significant effect size of 1.68 [95% CI, 0.52-2.84, Q(df=2) = 4.7, I2 = 56%]. For comparison, the Hedges’ g for ALPS in the individual pS6 experiment was 1.64 [0.18, 3.09]. (E-F) Representative images are shown of p4EBP1 staining (brown) for reactive lymph node (E) and iMCD-TAFRO (F). (G-H) Representative images are provided for p70S6K staining (brown) for reactive lymph nodes (G) and iMCD-TAFRO (H). All representative images have hematoxylin counterstain (blue) as a nuclear stain. Bar = 200 µm. *P < .05, **P < .01.