Patient characteristics.

<p>Patient characteristics.</p

Interassay variance.

<p>Figure shows standard curves (A1, B1) of single ELISA plates (grey) and mean standard curves (black) of nAbs-tau-ELISA (A1) and nAbs-αS-ELISA (B1). Furthermore, single (grey crosses) and mean ODs of the pooled serum standard (A2, B2) are displayed for nAbs-tau-ELISA (A2) and nAbs-αS-ELISA (B). Data are shown as the mean ± SD.</p

Distribution of the urea-mediated avidity reduction.

<p>For each non-demented (PDND) and demented Parkinson's disease (PDD) patient, nAbs-tau and nAbs-αS avidity reduction was calculated. Box plots show the median, 25% and 75% quartile. 50% of the generated data are located in the box and whiskers represent the minimum and maximum value. Significant differences were found within (PDND: ***<i>p</i> < 0.001; PDD: <i>p</i> = 0.057) but not between (PDND and PDD: <i>p</i> > 0.05) the patient groups.</p

Naturally Occurring Autoantibodies against Tau Protein Are Reduced in Parkinson's Disease Dementia - Fig 2

<p><b>Distribution of relative serum sample ODs of nAbs-tau- (A) and nAbs-αS-ELISA (B).</b> The relative serum sample OD (related to serum standard OD) of each non-demented (PDND) and demented Parkinson's disease (PDD) patient was determined without (nAbs) and with urea treatment (nAbs + urea). For an overview of their distribution, box plots show the median, 25% and 75% quartile. 50% of the generated data are located in the box and whiskers represent the minimum and maximum value. NAbs-tau OD showed significant differences between PDND and PDD patients (A; **<i>p</i> = 0.007). Treatment with 8 M urea caused significant reduction of ODs of nAbs-tau (A; PDND: ***<i>p</i> = 0.002; PDD: ***<i>p</i> < 0.001) and nAbs-αS (B; PDND: *<i>p</i> = 0.001; PDD: **<i>p</i> < 0.001).</p

Effects of short-term depletion treatments on plasma cell numbers in bone marrow and spleen.

<p><b>(A)</b> Representative FACS histogram of bone marrow and splenic CD138⁺ intracellular κ⁺ BrdU⁺ short-lived plasma cells (SLPCs), and CD138⁺ intracellular κ⁺ BrdU^- long-lived plasma cells (LLPCs) from each treatment group. Percentage of remaining cell numbers relative to the control mean of (<b>B)</b> bone marrow and (<b>C)</b> splenic CD138⁺ intracellular κ⁺ total plasma cells (PCs), SLPCs, and LLPCs in mice treated with PBS, anti-CD20, anti-CD20 plus integrin-blocking antibodies (Int; anti-LFA1 and anti-VLA4 antibodies), anti-CD20 plus bortezomib (Bz) and anti-CD20 plus Int and Bz. Total PCs, SLPCs and LLPCs were enumerated by flow cytometry 7 days after the start of treatment (<i>n</i> = 5–6 mice per each group). Values are mean±SEM; ns, non-significant; P>0.05, *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001, post-hoc test. Abbreviations: Bz, bortezomib; CD20, anti-mouse CD20 antibody; FMO, Fluorescence-minus-one; Int, Integrin blocking antibodies; anti-LFA1 and anti-VLA4 antibodies.</p

Effects of short-term depletion treatments on bone marrow and splenic T cells.

<p>Percentage of remaining CD3⁺ T cells, CD4⁺ T-helper cells, and CD8⁺ T-cytotoxic cells after one week of treatment in ratio to the mean of control in (<b>A)</b> the bone marrow, and (<b>B)</b> spleen. Values are mean±SEM; ns, non-significant, P>0.05, *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001, post-hoc test (<i>n</i> = 5–6 mice per group). Abbreviations: Bz, bortezomib; CD20, anti-mouse CD20 antibody; Int, Integrin blocking antibodies, anti-LFA1 and anti-VLA4 antibodies.</p

B cell depletion (BCD) maintenance therapy after short-term depletion (STD) of B and plasma cells with ant-CD20 and bortezomib improves the disease in NZB/W F1 mice.

<p>Mice (n = 4) were treated with anti-CD20 and bortezomib (STD) alone or continuous B cell depletion without bortezomib (BCD, n = 5) or treated as STD followed by BCD maintenance therapy with anti-CD20 (STD+BCD, n = 4). (<b>A)</b> Serum IgM and IgG anti-dsDNA antibody levels in treated and untreated mice (n = 9), as measured by ELISA. (<b>B)</b> Proteinuria in treated and untreated mice. Statistical differences between treated and untreated mice were analyzed using the post-hoc test (ns, non-significant, P>0.05, *<i>P</i><0.05; **<i>P</i><0.01, ***<i>P</i><0.001). (<b>C)</b> Survival curves for treated and untreated NZB/W F1 mice (Kaplan—Meier log-rank test). Abbreviations: STD, Short-term depletion (anti-CD20 and bortezomib); BCD; B cell depletion (anti-CD20).</p

Effects of short-term depletion treatments on the numbers of different B-cell subsets in bone marrow and spleen.

<p>Percentage of remaining B cell subsets in the bone marrow and spleen in ratio to the mean of control. (<b>A)</b> Bone marrow B-cell subsets identified by flow cytometry: total B cells (BCs) (CD19⁺), bone marrow pro-B cells (CD93⁺CD117⁺), pre-B cells (CD24⁺IgM^-IgD^-), immature B cells (CD24⁺IgM⁺IgD^-), and mature B cells (CD24^-IgM⁺IgD⁺). (<b>B)</b> Splenic B-cell subsets identified by flow cytometry: follicular (FO) B cells (CD23⁺CD21⁺IgM⁺), marginal zone (MZ) B cells (CD23^- CD21⁺IgM⁺), germinal center (GC) B cells (IgD^-GL7⁺), and B1 B cells (CD23^-CD21^-IgM⁺). Values are mean±SEM; ns, non-significant, P>0.05, *<i>P</i><0.05; **<i>P</i><0.01, ***<i>P</i><0.001, post-hoc test (<i>n</i> = 5–6 mice per group). Abbreviations: Bz, bortezomib; CD20, anti-mouse CD20 antibody; Int, Integrin blocking antibodies; anti-LFA1 and anti-VLA4 antibodies.</p

Additional file 1: Figure S1. of Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry

Proportions of patients with a JIA-ACR 30/50/70/90 response from month 3 until month 24 as compared to baseline (week 0). The number of patient scontributing to the calculation is given below the figure. (PPT 1206 kb

Prevalence rates of hypertension by age, sex and type of diagnosis.

<p>N = 55,518, † N = 53,337 patients with valid blood pressure assessment; %w = weighted percentages HTNdoc: doctor’s diagnosis; HTNdoc/pat: doctor’s or patient’s diagnosis; HTNdoc/pat/bp: doctor’s or patient’s diagnosis or blood pressure 140/90 mmHg; HTNHANES: blood pressure >140/90 mmHg or receiving antihypertensive therapy.</p