Absolute counts and correlation between CD4, CD8, and CD19 lymphocytes in sarcoidosis.

<p>A) Peripheral blood lymphocyte measurements show that 16 patients (57%) had lower than normal CD4 counts, 15 patients (54%) had lower than normal CD8 counts, and 15 patients (54%) had lower than normal CD19 counts. The box indicates the normal range for cell counts (95% of normal control subjects fell within this normal range) (p<4×10⁻¹⁰). B) Correlation between lymphocyte counts in sarcoidosis patients. CD4∶CD8 correlation shown in purple, and CD4∶CD19 shown in blue, with Spearman's rho and p-value indicated for each correlation.</p

Demographic and Clinical Information for the Cohort.

<p>Demographic and Clinical Information for the Cohort.</p

Lymphocyte counts in patients with severe organ system involvement vs. those without severe organ system involvement.

<p>Severe organ system involvement is defined as outlined in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009088#s2" target="_blank">methods</a>.</p

Relationship between peripheral blood markers and number of episodes.

<p>Expression of five immune transcripts overexpressed in patients with history of relapse correlates with number of past TTP episodes. Serum ADAMTS13 activity does not correlate with number of past episodes (upper left panel). Y-axis is percent of full activity for ADAMTS13 as measured by FRET assay (upper left panel). Y-axis is gene expression in normalized units for the five immune genes (all other panels). Spearman R values are shown.</p

Type I IFN and ribosomal gene expression signature associations.

<p>(A) Association of the type I IFN gene signature with antibodies to RNA binding proteins (RBP) but not relapse history. (B) Association of the ribosomal gene signature (RGS) with relapse history but not antibodies to RBP. Proportions were compared using Fisher’s exact test. Odds ratios (OR) were calculated as described in Materials and Methods.</p

Characteristics of TTP remission cohort^a.

<p>^a Individuals with a history of clinically diagnosed TTP (<10% ADAMTS13 activity during a prior acute episode), in remission for at least 2 months, who fail to meet criteria for any known rheumatic disease;</p><p>^b t-test;</p><p>^c Fisher’s exact test;</p><p>^d Kolmogorov-Smirnov test.</p><p>Characteristics of TTP remission cohort<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0117614#t001fn001" target="_blank">^a</a>.</p

Relationship of relapse-over-expressed immune genes to the ribosomal gene signature.

<p>(A) Association of increased <i>HLA-DRB1</i> and <i>HLA-DRB5</i> expression with history of relapse. Proportions were compared using Fisher’s exact test. Y-axes are in normalized units. Expression levels >400 normalized units were considered high. (B) Positive correlation of the patient ribosomal gene signature with expression of seven of eight immune genes over-expressed in relapse patients. Spearman r values are shown. Y-axes are in normalized units.</p

Direct comparison of gene expression of peripheral blood samples between patients with or without a history of relapse.

<p>(A) Average normalized ribosomal gene signature expression values in patients with or without a history of relapse. Error bars depict standard error of the mean. Expression values were compared using Student’s t-test. (B) Relative expression levels of genes differentially expressed between relapse and non-relapse patients presented following clustering. Colors indicate relative increased (red) or decreased (green) expression.</p

Association of RGS, HLA DR gene expression or combination thereof with relapse in ADAMTS13-deficient TTP.

<p>^a Odds ratios (OR) estimated by modified median unbiased estimation (MMUE) due to zero cells;</p><p>^b Confidence intervals (CI) estimated by exact, bootstrapped MMUE;</p><p>^c Fisher’s exact test, 2-tailed.</p><p>Association of RGS, HLA DR gene expression or combination thereof with relapse in ADAMTS13-deficient TTP.</p

Expression of CD52, CD244 and CD161 protein on the cell surface of CD3^-CD56^dim NK and CD3⁺ T cells isolated from relapsed ADAMTS13-deficient TTP patients in remission.

<p>Mean fluorescence intensity (MFI) of CD52, CD244 and CD161 on CD3^-CD56^dim and CD3^-CD56^bright NK cells (A) and on CD3⁺ T cells (B) derived from relapsed (R) or non-relapsed (NR) TTP patients. Representative histograms of fluorescence intensity of markers exhibiting significant differences between relapse (thick, dashed lines) and non-relapsed (thin, solid lines) patients are shown in C. (relapse n = 9, non-relapse n = 13, <i>Mann-Whitney test</i>; **p<0.01).</p