Summary of the results of lumbar puncture (LP) in patients with primary progressive multiple sclerosis (PPMS).

<p>Summary of the results of lumbar puncture (LP) in patients with primary progressive multiple sclerosis (PPMS).</p

Spearman correlation (ρ) between CSF-lactate and EDSS at the lumbar puncture (EDSSLP) and the yearly progression rate in the entire cohort, treatment-naïve PPMS patients (PPMSTN) and at the LP at the year of diagnosis (LPD).

<p>Spearman correlation (ρ) between CSF-lactate and EDSS at the lumbar puncture (EDSSLP) and the yearly progression rate in the entire cohort, treatment-naïve PPMS patients (PPMSTN) and at the LP at the year of diagnosis (LPD).</p

Correlation between CSF-lactate and EDSSLP and yearly progression rate in the entire cohort, EDSSLP and LPD.

<p>Spearman correlation between the CSF-lactate and expanded disability score scale at the LP (EDSS_LP) and yearly progression rate showed consistently statistically significant positive correlation in the entire cohort, treatment-näive patients PPMS_TN and in the results of the diagnostic LP (LP_D). On the other side, a significant correlation between CSF-lactate and EDSS_LP was found only in the LP_D.</p

Prevalence of single positive AI against measles (M), Rubella (R) and varicella-zoster virus (Z) and different combinations in our PPMS cohort.

<p>Prevalence of single positive AI against measles (M), Rubella (R) and varicella-zoster virus (Z) and different combinations in our PPMS cohort.</p

Clinical features of primary progressive multiple sclerosis (PPMS) patients.

<p>Clinical features of primary progressive multiple sclerosis (PPMS) patients.</p

(A) Hematoxylin and eosin staining of liver sections obtained from CYP2D6 and FVB/N mice infected with either Ad-2D6 or Ad-GFP at weeks 1, 4, and 8 after infection

Note that persistent hepatic damage (massive cellular infiltrations and significant necrosis) is present in Ad-2D6–infected mice only. Infection of FVB/N mice with Ad-GFP results in a similar histology as Ad-GFP infection of CYP2D6 mice (not depicted). Bars, 50 μm. (B) The following scoring system was used to assess liver infiltration: 0, no visible infiltration; 1, few focal infiltrates; 2, numerous scattered focal infiltrates; 3, few large clusters of infiltrating cells (perivascular or subcapsular); 4, numerous large clusters of infiltrating cells occupying >50% of portal tracts or central veins; and 5, confluent periportal infiltrates. The presented data are mean infiltration scores ± SEM. Statistical analysis (Mann-Whitney test) revealed significant differences between mice infected with Ad-2D6 or Ad-GFP at the indicated times after infection. *, P < 0.05. The number of individual mouse livers analyzed per experimental group is indicated at the bottom of each data column. (C) Immunohistochemistry of liver sections of wild-type FVB/N and humanized CYP2D6 mice at week 2 after infection with Ad-2D6. Cellular infiltrations consisted predominantly of B cells (B220), CD4 T cells, and macrophages (F4/80). Bars, 50 μm.<p><b>Copyright information:</b></p><p>Taken from "Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection"</p><p></p><p>The Journal of Experimental Medicine 2008;205(6):1409-1422.</p><p>Published online 9 Jun 2008</p><p>PMCID:PMC2413037.</p><p></p

(A) Pictures of representative end results of total IgG or CYP2D6-specific spot-forming assays

Colored spots indicate the reaction of enzyme-labeled secondary antibodies against secreted IgG and represent one antibody-secreting cell. (B) Quantification of total IgG (top) and CYP2D6-specific IgG (bottom)–secreting cells per 10 splenocytes in FVB/N and CYP2D6 mice at the time points indicated. Note that B cells secreting CYP2D6 antibody–specific antibodies were only detectable after Ad-2D6 infection. ND, not detectable. (C) IgM and IgG type anti-CYP2D6 antibody generation in FVB/N and CYP2D6 mice infected with either Ad-2D6 or Ad-GFP over time. Data are mean ± SEM. (D) Representative pictures of rat liver sections stained with sera from Ad-2D6–infected CYP2D6 mice, Ad-2D6–infected FVB/N mice, AIH-1 patients (ANA), AIH-2 patients (LKM-1), and PBC patients (antimitochondrial antibodies), followed by Alexa Fluor 488–conjugated anti–mouse IgG or FITC-conjugated anti–human IgG secondary antibody. Bars, 50 μm.<p><b>Copyright information:</b></p><p>Taken from "Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection"</p><p></p><p>The Journal of Experimental Medicine 2008;205(6):1409-1422.</p><p>Published online 9 Jun 2008</p><p>PMCID:PMC2413037.</p><p></p

(A) Paraformaldehyde-fixed livers of CYP2D6 mice infected with either Ad-2D6 or Ad-GFP at week 8 after infection

Bars, 0.5 cm. (B) LDS for evaluation of the morphological appearance of mouse liver after adenovirus infection. Pictures of representative livers of LDS 0 (Ad-GFP infected) and LDS 5 (Ad-2D6 infected) are shown in A. (C) Livers of CYP2D6 and FVB/N mice infected with either Ad-2D6 or Ad-GFP were harvested at several times after infection, and LDS was determined by morphological examination. The mean LDS for each group is indicated by horizontal lines. Note that Ad-2D6–infected mice only develop persistent liver damage. Statistical analysis (Mann-Whitney test) revealed significant differences between Ad-2D6 and Ad-GFP mice at the indicated times. *, P < 0.01; **, P < 0.05.<p><b>Copyright information:</b></p><p>Taken from "Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection"</p><p></p><p>The Journal of Experimental Medicine 2008;205(6):1409-1422.</p><p>Published online 9 Jun 2008</p><p>PMCID:PMC2413037.</p><p></p

(A) SPOTs membrane containing staggered peptides of 12 aa in length covering the entire 497 aa of the human CYP2D6 molecule

The membrane was developed with serum of an Ad-2D6–infected CYP2D6 mouse. Numbers indicate the position within the CYP2D6 sequence of the first aa of the first peptide spot in each horizontal lane. (B) Quantification of the serum reactivity profile to SPOTs peptides. Representative serum samples of an Ad-2D6–infected CYP2D6 mouse, an Ad-2D6–infected FVB/N mouse, an AIH-2 patient, and an AIH-1 patient. Numbers indicate the aa position within the human CYP2D6 sequence. (C) For an overview of the epitope profile, the human CYP2D6 sequence was divided into 20 25-aa-long sections, as indicated at the top of each column. Signal intensities of sera from Ad-2D6–infected CYP2D6 and FVB/N mice, patients with AIH-2, and patients with other autoimmune liver diseases, such as AIH-1, AIH-3, or PBC, are indicated in red (strong), orange (medium), gray (low), and white (no reactivity). Note that the region containing the immunodominant WDPAQPPRD epitope (region 251–275) is recognized by all sera of Ad-2D6–infected CYP2D6 and FVB/N mice, as well as by all tested sera of AIH-2 patients, but not by sera from patients with other autoimmune liver diseases.<p><b>Copyright information:</b></p><p>Taken from "Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection"</p><p></p><p>The Journal of Experimental Medicine 2008;205(6):1409-1422.</p><p>Published online 9 Jun 2008</p><p>PMCID:PMC2413037.</p><p></p

(A) Expression of GFP in liver sections at several times after infection of CYP2D6 mice with Ad-GFP

Bars, 50 μm. (B) Serum levels of ALT and AST in humanized CYP2D6 and wild-type FVB/N mice infected with Ad-2D6 or Ad-GFP at several times after infection. Note that elevations in serum ALT and AST were transient and not persistent. Statistical evaluation ( test) revealed no significant differences in AST and ALT augmentation curves over time between Ad-2D6– and Ad-GFP–infected mice (FVB, P = 0.7 [ALT] and 0.79 [AST]; CYP2D6, P = 0.5 [ALT] and 0.13 [AST]) and between FVB/N and CYP2D6 mice (Ad-2D6, P = 0.64 [ALT] and 0.59 [AST]; Ad-GFP, P = 0.31 [ALT] and 0.82 [AST]). (C) Serum levels of AP in humanized CYP2D6 and wild-type FVB/N mice infected with Ad-2D6 or Ad-GFP at several times after infection ( = 5 per group). Transient AP elevation was detected in CYP2D6 and FVB/N mice at weeks 1 and 2 after infection with Ad-2D6 but not Ad-GFP. Statistical evaluation ( test) revealed significant differences in serum AP compared with preinfection levels (week 1, P = 0.035 [FVB/N Ad-2D6]; week 2, P = 0.044 [FVB/N Ad-2D6] 0.029 [CYP2D6 Ad-2D6]) and between Ad-2D6– and Ad-GFP–infected mice (week 1, P = 0.03 [FVB] and 0.063 [CYP2D6]; week 2, P = 0.055 [FVB] and 0.029 [CYP2D6]). Data are mean ± SD.<p><b>Copyright information:</b></p><p>Taken from "Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection"</p><p></p><p>The Journal of Experimental Medicine 2008;205(6):1409-1422.</p><p>Published online 9 Jun 2008</p><p>PMCID:PMC2413037.</p><p></p