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e.ebi.ac.uk/pride/data/archive/2019/04/PXD008344/F242323.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/04/PXD008344/F242348.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/04/PXD008344/F242382.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/04/PXD008344/F242298.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/04/PXD008344/F242293.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/04/PXD008344/F242321.datftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/04/PXD008344/F242372.datprimaryOK200Wolfgang FaigleNot availableBrainWhite MatterGray MatterSample processing protocol: Barocycler instrument (Barocycler 2320EXT) from Bioscience (Pressure BioSciences, Inc, South Easton, MA) was used to extract proteins from frozen tissue. Samples of 2-3mg were put into barocycler 150l micro tubes. The tubes were filled with 30l of lysis buffer (8M urea and 0.1M bicarbonate) and complete protease inhibitor cocktail (Roche, Switzerland) and closed with 150 l microcaps. The barocycler instrument was pre-heated for 30 min. at 33°C. Run cycles were performed at 45 kpsi for 60 cycles and 1 min each. Each cycle lasted 50 sec. at high pressure and 10 sec. at ambient pressure at 33°C. Reduction and alkylation were carried out as follows: Mixing of TCEP 2.5mg and IAA 3.7mg in 50 l of lysis buffer. A volume of 4.88 l of this buffer was added to each l pestle tube, incubated at 25°C in a thermomixer while shaking at 1000rpm and protected from light. By adding lysis buffer, the urea concentration was diluted from 8M to 6M. Lys-C enzyme digestion was applied to an enzyme to substrate ratio of 1:40. Lys-C (mass spectrometry grade, Wako, Richmond, VA, USA 20g/l) was dissolved in “Milli-Q-water” to a final concentration 4g/l. Digestion was performed in barocycler with 20kpsi for 45 min. and cycles of 50 sec. duration at high pressure and 10 sec. ambient pressure. A further dilution of urea from 6M to 1.6M with 0.1 M ammonium-bicarbonate buffer was necessary to achieve trypsin digestion conditions. Trypsin (sequencing grade modified, Promega, Madison, WI, USA) was added to an enzyme to substrate ratio 1:20. The digestion took place for 90 min. at 37°C in a barocycler at 20kpsi and cycle periods of 50 sec. at high pressure and 10 sec. at ambient pressure. Finally, the solution was transferred to a 1ml Eppendorf tube. The volume was adjusted to 1ml by adding a 0.1%TFA/ 3%ACN solution. The reaction was stopped by adding 10%TFA and pH adjusted to a value between pH 2 and 3. The peptides need to be “cleaned” on solid phase extraction columns (C18/17% Finisterre, Wicom Germany). Columns were pre-wet with methanol followed by 1ml of 60%ACN/ 0.1%TFA. Equilibration step of the columns with 1 ml of 3%ACN/ 0.1%TFA. This step was repeated twice. The columns were washed 6 times with 1 ml of 3%ACN 0.1%TFA and the peptides eluted with 1 ml of 60%TFA 0.1%TFA and subsequently with 400l of 100% ACN. The samples were vacuum dried in a “SpeedVac" at 45°C and the peptides re-dissolved in 3% ACN/0.1% formic acid in a volume of 20-50l to obtain a concentration of 1g/l. Peptide concentration was measured with Nanodrop instrument (Nanodrop 1000, spectrophotometer (Thermo Scientific, Wilmington, DE, USA) and a solution of a concentration of 0.5g/l prepared. Hydrophilic Interaction Chromatography (HILIC) Pools of peptide samples of the healthy tissue (HD), as well as the MS tissues, were prepared (300g each) and separated on a hydrophilic interaction liquid chromatography (HILIC) (Agilent LC1200 equipped with a column Polyamin II 250 x 3.0 mm 120 Å, 5m). The gradient applied was made of the two solvents: A: 75 ACN%, 8mM KH2PO4 and B: 5%ACN, 100mM KH2PO4 (pH4.0) for 60 min. Fractions of 1 ml were collected in 27 tubes. To reduce the number of the samples to analyze on mass spectrometer the fractions were pooled from two tubes. Before injection, samples were purified on “Finisterre SPE” columns (Wicom international). For “cleaning-up” peptides after digest, the same protocol as mentioned above was applied. Samples of 1ml were vacuum dried and dissolved in an appropriate buffer, 3%ACN /0.1 %TFA. In total 11 fractions for each sample (HD and MS) were prepared. After another vacuum drying, peptides were dissolved in 3%ACN/ 0.1%FA buffer. Concentrations were measured with Nanodrop instrument and adjusted to 0.25g/l. Reference peptides (IRT) were added (iRT, Biognosys, Switzerland) to each sample. Data dependent analysis (DDA) of the HILIC fractionated samples The HILIC fractionated samples, 44 in total, were run on Easy-nLC 1000 linked to an Orbitrap Fusion instrument (Thermo Fisher) on a gradient of 80min. Column material was ReproSil-Pur, C18, 120 Å, AQ, 1.9 µm (Dr. Maisch GmbH) and column dimensions ID 0.075mm/ length 150mm. Solvent A 0.1% formic acid in water and Solvent B 0.15 formic acid in acetonitrile. 4l of the sample at a concentration of 0.25l/l was injected.PrideProf. Dr. Roland MartinQ ExactivePARTIALNeuroimmunology and MS Research University Hospital Zurich Frauenklinikstrasse 26 8091 Zurich Switzerland31024521 Faigle W, Cruciani C, Wolski W, Roschitzki B, Puthenparampil M, Tomas-Ojer P, Sellés-Moreno C, Zeis T, Jelcic I, Schaeren-Wiemers N, Sospedra M, Martin R. Brain Citrullination Patterns and T Cell Reactivity of Cerebrospinal Fluid-Derived CD4+ T Cells in Multiple Sclerosis. Front Immunol. 2019 10:540 10.3389/fimmu.2019.00540University Hospital Zurichroland.martin@usz.chMass SpectrometryTop-down proteomicsMultiple SclerosisPost-translational modification(mbp)CitrullinationPressure cycle technology (pct)Human post mortem brain tissueHydrophilic interaction liquid chromatography hilicNeurodegenerationMultiple sclerosis (ms)Mass spectrometryMyelin basic proteinhttp://www.ebi.ac.uk/pride/archive/projects/PXD008344Spectrum countingiodoacetamide derivatized residuedeamidated residueacetylated residue“Raw” files were converted into “mgf” files and analyzed on MASCOT software with a human UniProtKB/Swiss-Prot protein database (date: March 22, 2016 with 40912 entries): Search parameters were 0.05Da fragment mass tolerance and 10ppm precursor mass, minimal number of peptides 2, and FDR (false discovery rate) of 0.1%, allowing 2 mis-cleavages on trypsin fragments. Carbamidomethyl at cysteine was set as a static modification, and oxidation of methionine, deamidation on R (with or wihout neutral loss), Q and N was set as variable modification. To estimate FDR’s separately for deamidated and all the other proteins the mascot dat files were converted to the bibliospec file format. For each unique peptide sequence the best peptide spectrum match (the one with the highest mascot score) was selected. Then the modified peptide FDR was commuted. Protein identifications (ID) were assigned to peptide sequences using the R-package “prozor”. The resulting tables were exported so they could be further analyzed in excel. Peptide identification with Ursgal The universal python module combining bottom-up proteomics tools for large-scale analysis (ursgal) was used to perform a search with multiple search engines (xtandem vengeance, msgfplus_v9979 and myrimatch 2 2 140) (Kremer et al. 2016). Evaluation and post processing of the search results was performed using percolator_2_08. The workflow was based on a modified version of the do_it_all_folder_wide.py ursgal example script and the modified file is available as supplement (see Supplement X). The variable and fixed modifications were set in the same way as the mascot settings. For instrument settings, the Q-Exactive+ ursgal profile is used. The “unified_percolator_validated.u_merged_accepted.u_merged.csv” tables (see Supplement X), generated by ursgal, where than loaded into R. For each peptide the best PSM is then selected according the lowest PEP and q.value score. The FDR on peptide level was re-estimated for the deamidated and all the other peptides separately, based on target-decoy information and the percolator PEP score. The results were exported to tsv files in long and wide format so that FDR filtering and further analysis can be performed in excel.ProteomicsHomo Sapiens (human)wolfgang.faigle@usz.chBiomedicalSwitzerlandImmune responses to citrullinated peptides have been described in autoimmune diseases like rheumatoid arthritis (RA) and multiple sclerosis (MS). We investigated the post-translational modification (PTM), arginine to citrulline, in brain tissue of MS patients and controls (C) by proteomics and subsequently the cellular immune response of cerebrospinal fluid (CSF)-infiltrating T cells to citrullinated and unmodified peptides of myelin basic protein (MBP). Using specifically adapted tissue extraction- and combined data interpretation protocols we could establish a map of citrullinated proteins by identifying more than 80 proteins with two or more citrullinated peptides in human brain tissue. We report many of them for the first time. For the already described citrullinated proteins MBP, GFAP, and vimentin, we could identify additional citrullinated sites. The number of modified proteins in MS white matter was higher than control tissue. Citrullinated peptides are considered neoepitopes that may trigger autoreactivity. We used newly identified epitopes and previously reported immunodominant myelin peptides in their citrullinated and non-citrullinated form to address the recognition of CSF-infiltrating CD4<sup>+</sup> T cells from 22 MS patients by measuring proliferation and IFN-γ secretion. We did not detect marked responses to citrullinated peptides, but slightly more strongly to the non-modified version. Based on these data, we conclude that citrullination does not appear to be an important activating factor of a T cell response, but could be the consequence of an immune- or inflammatory response. Our approach allowed us to perform a deep proteome analysis and opens new technical possibilities to analyze complex PTM patterns on minute quantities of rare tissue samples.Brain Citrullination Patterns and T Cell Reactivity of Cerebrospinal Fluid-Derived CD4<sup>+</sup> T Cells in Multiple Sclerosis.Faigle Wolfgang W, Cruciani Carolina C, Wolski Witold W, Roschitzki Bernd B, Puthenparampil Marco M, Tomas-Ojer Paula P, Sellés-Moreno Carla C, Zeis Thomas T, Jelcic Ivan I, Schaeren-Wiemers Nicole N, Sospedra Mireia M, Martin Roland Rsodium salt, CPD photolyase activity, concentration., ammonium formate, 13C-labeled, cadmium salt, MeCN, PhrB photolyase activity, NCMe, determination, fond, instrument configuration, zinc formate, lead salt, Visible Light, protein, Basodexan, 2-(indol-3-yl)ethanoic acid, magnesium formate, CycEI, lysis, pigmented epithelium, extracted material, zinc salt, Solvent, Alkylations, peptide, Polypeptides, protein polypeptide chains, ammonium tetraformate, Ccne, IAA, peptido, ClvPrd, BANF, cobalt(II) formate dihydrate, azanium, GRP1, CH3-C#N, hnu, Grp1, B1, SEC, Urea, 3, Min, NUP96, Analysis, outer pigmented layer of retina, protein aggregate, epithelium, Injectables, foton, DmelCG42273, wood alcohol, Mass Spectrum Analysis, portion of tissue, Divorced, C79325, peptides, Analyses, E927b, 2610036I19Rik, PTPSTEP, sec, Tissue, 2610510L13Rik, pigmented retina, min, mAPC, proteins, Divorces, number of, copper, DNA cyclobutane dipyrimidine photolyase activity, SUPPRESSOR OF AUXIN RESISTANCE 3, AI047805, reaction, fSAP152, pigment epithelium of retina, lithium salt, column, anatomical tube, ACN, l(2)k08110, sample, Acn, Solid Phase Extractions, D1, high pressure, pigmented retina epithelium, autolysin activity, necrosis, Sodium Methoxide, ammonium (2:1) salt, Ammonium(1+), gamma, GPH, nickel salt, ratio, PRE, Tube, Radiation, Alcohol, cobalt (+2) salt, Trypsin/K, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, Liquid Chromatography, Dmel_CG7826, Light, extra or missing physical or functional parts, pigmented retinal epithelium, Cyc E, br37, Spectrum Analysis, Thermo Scientific, ur, Spectroscopy, TUBE, carbamide, NH4(+), (Indol-3-yl)acetate, sodium (4:1:1) salt, LIGHT, BG:DS07108.3, retinal pigment, Dm1, magnesium salt, 3.1.3.48, tissue portion, dipyrimidine photolyase (photosensitive), bacteriocin activity, simple tissue, IES, l(2)05206, nickel (+2) salt, Carbinol, retinal pigment layer, Dmel_CG7835, Hydrogen Oxide, carbinol, Mnb, MNB, Visible Radiations, ammonium salt, Visible Radiation, HVEML, instrument, Step, CG11628, retinal pigmented epithelium, proportionality, formate, Spectrometry, cobaltous formate, pooled, rate, cromium (+3), Striatum-enriched protein-tyrosine phosphatase, AW124434, study protocol, beta Trypsin, Solid Phase, METHANOL, H2NC(O)NH2, phr A photolyase activity, Indole-3-acetic acid, Wood, lysin activity, light quantum, DNA-photoreactivating enzyme, l35Dd, heteroauxin, STEP, spirit of wood, duct, copper salt, bacteriolytic toxin activity, ammonium (4:1) salt, Polypeptide, methyl cyanide, lead (+2) salt, 1728, time, Methyl Alcohol, Ammonium, cycline, GRP1/cytohesin 1, nickel formate dihydrate, lead formate, DmcyclinE, aluminum salt, cesium salt, number, Gene, Methyl, Carbamide, cycE, CH3OH, Spectrum Analyses, ACINUS, photoreactivating enzyme activity, protein-containing complex, Methylalkohol, l(2)br37, [NH4](+), deoxyribodipyrimidine photolyase activity, CG7826, stratum pigmentosum retinae, CYCLE, Buffer, Ly113, formic acid, cdi7, CG11633, Karbamid, period, cytohesin/GRP1, ammonium cation, method, potassium salt, cyclinE, polypeptide chain, Injection, 14C-labeled, method used in an experiment, Harnstoff, Gene Products, CG7835, Cdi7, CDI7, Mass, CG42273, Wood Alcohol, stratum pigmentosa retinae, light, Carmol, Separated, Mass Spectroscopy, Pro-Mega, T6K12_14, proportion, MOS3, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, CYCE, PRECOCIOUS, 2310061K05Rik, Acinus, thallium (+1) salt, DmelCG3938, Lichtquant, CyclE, ammonium ion, Selb, beta-Trypsin, rubidium salt, F23A5.3, 3938, l(2)SH2 0323, blocked, Extractions, Indoleacetic acid, Visible, methanol, DmcycE, calcium formate, methanoic acid, Solution, acinusL, l(2)k05007, Injectable, dm-cycE, Neural-specific protein-tyrosine phosphatase, 10^[-6], (indol-3-yl)acetic acid, acinusS, wood naphtha, has or lacks parts of type, photon, peptidos, cromium (+3) salt, TR2, Chromatographies, F23A5_3, sodium formate, TCEP, PTHB1, 1H-indol-3-ylacetic acid, DYRK1, data, nickel formate, 1-(14)C-labeled, 3H-labeled, protein complex, Proteins, strontium formate, NH4+, Methyl alcohol, stepk, potassium formate, copper (+2) salt, Extraction, strontium salt, acetonitrile, buffer, CD258, mKIAA0670, Peptide, Methanol, mereological quality, polypeptide, stratum pigmentosum (retina), MODIFIER OF SNC1, secret agent, l(2)k02514, native protein, DmCycE, natural protein, carbonyldiamide, C18, cupric formate, Protein, chemical analysis, deoxyribonucleic photolyase activity, AI551343, Sodium, Dyrk1, MeOH, CyeE, Vacuums, aluminum formate, l(2)SH0323, dJ142L7.2, ACETONITRILE, Mass Spectrum Analyses, cyanomethane, T6K12.14, Radiations, CYH1, AU020952, Mass Spectrum, Separation, RPE, lithium formate, holin, l(2)k02602, ammonium, uree, photolyase activity, HVEM-L, urea, Separations, CC1, l(2)35Dd, Photoradiation, 3-Indolylessigsaeure, Tripcellim, ethanenitrile, retinal pigment epithelium, sample population, chromic formate, UREA, LTg, DmelCG11628, p. pigmentosa retinae, ME-IV, plan specification, Protein Gene Products, Gene Proteins, D-CycE, Trypure, Photoradiations, Pressures, concentration, wood spirit, cardinality, quotient, calcium salt, Peptid, deoxyribonucleate pyrimidine dimer lyase (photosensitive), assay, SCH, CG3938, Methoxidethe brain, "multiple sclerosis" EXACT [NCI2004_11_17:C3243], Cerebro Spinal Fluid, Disseminated Sclerosis, suprasegmental structures, insular sclerosis, T-cell surface antigen T4/Leu-3, T-cell surface antigen T4|Leu-3, FON1, Sclerosis, Deimination, Multiple Sclerosis, Fluids, Cerebrospinal Fluids, SUPERMAN, spinal fluid, Synaptosomal-associated 25 kDa protein, MS (Multiple Sclerosis), FLORAL ORGAN NUMBER 1, encephalon, Protein-Arginine Deimination, Spinal Fluid, Cerebrospinal, Cerebro Spinal Fluids, Spinal Fluids, L3T4, MS, "Multiple sclerosis" EXACT [SNOMEDCT_2005_07_31:155023009], Fluid, cerebral spinal fluid, T-cell differentiation antigen L3T4, responsivity, Protein, SUP, Ly-4, Cerebro Spinal, liquor cerebrospinalis, GENA70, "Generalized multiple sclerosis (disorder)" EXACT [SNOMEDCT_2005_07_31:192928003], synganglion, Peptidylarginine Deimination, immature T cell, T lymphocyte, "Multiple sclerosis (disorder)" EXACT [SNOMEDCT_2005_07_31:24700007], reactivity, "Multiple sclerosis NOS (disorder)" EXACT [SNOMEDCT_2005_07_31:192930001], T-cell, T-cell surface glycoprotein CD4, Encephalon, Protein Arginine Deimination, Bdr, Protein Deimination, CD4mut, "insular sclerosis" EXACT [CSP2005:2042-2324], FLO10, CSF, suprasegmental levels of nervous system, T-lymphocyte, Super protein, Cerebro, HERP, Disseminated, sp, SNAP-25, Acute Fulminating, Mif1, Multiple, T cell, generalised multiple sclerosis, mature T cell, CD4, response, generalized multiple sclerosis, "Multiple sclerosis" EXACT [ICD9CM_2006:340]., FLORAL DEFECTIVE 10SH2-Bb, 70zpep, IPP2A2, scale tissue, dmBest1, PEP/X4, PP14, PKDYS, determination, DmelCG30170, LYP2, b(2)gcn, LYP1, instrument configuration, Mbp1, Irip, protein, NAALAdase, DmelCG6264, DmelCG6143, 5730420M11Rik, peptide, Polypeptides, NAALADase I, protein polypeptide chains, L-Isomer Methionine, FOLH, Drug Tolerance, Methionine, peptido, ClvPrd, MIF, Pop, ARB, C530001K22Rik, Software Engineering, 3.4.17.21, MIS, DA transporter, protein aggregate, Work Flow, myd, Computer Program, WMS, C79691, SH2-B, somitogenic mesoderm, LyP, SET, F, peptides, Dlp1, Membrane glutamate carboxypeptidase, TAF-I, M, plant peltate hair, long, Open, phosphatase 2A inhibitor I2PP2A, Computer Programs and Programming, chemical analysis., Mbp-1, X4/PEP, proteins, PEPPER, number of, NAALAD1, Estimated, Folylpoly-gamma-glutamate carboxypeptidase, Lccp, DmelCG4299, LYP, set, IGAAD, Lymphoid phosphatase, DmelCG10574, Solute carrier family 6 member 3, PrEP, Half Cystine, PAEG, F12B17_170, GPHYSD2, Racemethionine, fs(2)eo-C, drug tolerance, SGS, ratio, phapii, CG6264, wide/broad, CG6143, PLATEST, Zinc Cysteinate, gyltl1b-b, unsegmented mesenchyme, immune system tolerance, T5E21.12, 2-Amino-4-(methylthio)butyric acid, StF-IT-1, ben(2)gcn, extra or missing physical or functional parts, Search, PEPINO, SH2-B PH domain-containing signaling mediator 1, Source Softwares, results, Software Tools, Programs, ACMICD, Program, Computer Applications, Workflows, PSM, Psm, MDDGA6, mKIAA0609, Computer Applications Software, 3.1.3.48, Computer Applications Softwares, Immunologic Tolerance, Methionin, methionine, Softwares, Hmet, presumptive somite mesoderm, Prostate-specific membrane antigen, TU15B, fixed, T5E21_12, dBest1, parent ion, fg, Pteroylpoly-gamma-glutamate carboxypeptidase, PEST-domain phosphatase, Software Applications, bcgn, gyltl1b, HLA-DR-associated protein II, F20B18.110, DI-2, instrument, Source Software, I-2Dm, FGCP, Drp1, dbest1, proportionality, mdc1d, expanded, F20B18_110, rate, MASCOT, L-Cysteine, AI047692, MASS, CG4299, inhibitor of granzyme A-activated DNase, beta Trypsin, human, GD, I-2PP1, Pro-rich, MDC1D, Applications, wide, GdA, Self Tolerance, TAF-IBETA, Tolerance, precursor ion, enr, GdF, enlarged, PNBP, PSMA, TAF-Ibeta, Polypeptide, GdS, i2pp2a, Liquimeth, PEP, cg10331, Work Flows, Platelets, Computer Software Applications, AI450666, Dnmlp1, big, SH2 domain-containing protein 1B, human being, Cysteine Hydrochloride, 2-amino-4-(methylsulfanyl)butanoic acid, AW549739, False, Peptidomics, peltate hair, number, unsegmented paraxial mesoderm, L Isomer, tables, FBN, gcn, Gene, Computer, precursor, broad, protein-containing complex, anon-WO0118547.380, pep, somitomeric mesoderm, GCPII, PHAPII, froggy, Gyltl1a, fs(2)eo6, python, large, CG30170, polypeptide chain, template-activating factor I, ECTOL1, Gene Products, Anti-Muellerian hormone, L-Methionine, N-acetylated-alpha-linked acidic dipeptidase I, mKIAA1299, Half-Cystine, Pedameth, Application, Open Source Softwares, Search Engines, SH2B, proportion, Software Application, L Cysteine, VMD2, MDDGB6, ipp2a2, beta-Trypsin, Open Source Software, 2pp2a, mGCP, BMD, man, CG10331, CG10574, Computer Software Application, CG10330, OCTD, mKIAA0989, BPFD#36, Table, 2PP2A, 2-amino-4-(methylthio)butanoic acid, Tools, taf-ibeta, PASTICCINO 2, great, has or lacks parts of type, BGCN, dSET, dSet, scale (sensu Metazoa), peptidos, DAT, metionina, Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP, RP50, Applications Software, Open Source, DAT1, Computer Software, DL-Methionine, protein complex, Bgcn, Proteins, igaad, D10Wsu136e, b(2)cgn, Muellerian-inhibiting substance, L-Isomer, AMH, Peptide, Engine, Tool, GCP2, mereological quality, Glutamate carboxypeptidase II, polypeptide, Software Tool, Cell growth-inhibiting gene 27 protein, native protein, Immune Tolerance, natural protein, I-2PP2A, Protein, Dm I-2, chemical analysis, I2PP2A, sequence, p100, MFS1, segmental plate, scales, Sh2bpsm1, Software, Dat1, Data Base, WMS2, Met, F12B17.170, Dbest, PH and SH2 domain-containing signaling mediator, scale, best, Ptpn8, Engineering, Tripcellim, fs(2)eoQS2, 6330417M19Rik, primary structure of sequence macromolecule, Folate hydrolase 1, Protein Gene Products, Computer Programs, Trypure, Gene Proteins, dSET/TAF-Ibeta, 2610030F17Rik, Applications Softwares, SSKS, cardinality, AI425885, quotient, alpha-amino-gamma-methylmercaptobutyric acid, Peptid, assay, PE, AI450383, variable, PTPN8, AA407739, BEST, Immunological TolerancePresenile Alzheimer Dementia, Parkinson's disease, posttranslational modification, ALZHEIMERS DIS, Unspecified disorder of immune mechanism, Early Onset, Parkinson's disease NOS, MBP-C, MBP1, Neurologic Diseases, protein, Neurologic Degenerative Condition, Rheumatoid arthritis NOS, Alzheimer's disease, Other specified disorders of the immune mechanism (disorder), Rheumatoid disease, Neurodegenerative Diseases, RhA - Rheumatoid arthritis, AD, protein polypeptide chains, unspecified, Other specified disorders involving the immune mechanism, Neurologic Disorders, RA, synganglion, Arthritis or polyarthritis, protein aggregate, Autoimmune, Nervous System Degenerative Diseases, Eosinophil granule major basic protein, HSMBPC, portion of tissue, DEFIC CELL IMMUNITY NOS, oligodendrocyte myelin sheath, LATE ONSET ALZHEIMER DIS, posttranslational amino acid modification, Degenerative Condition, Deficiency of cell-mediated immunity, Parkinson disease, Autoimmune disease, rheumatic, Arthritis, DAT - Dementia Alzheimer's type, Parkinson's disease (disorder), [X]Disorder involving the immune mechanism, rheumatoid, Tissue, Immune System and Related Disorders, glial fibrillary acidic protein., proteins, Alzheimer's dementia, Myelin membrane encephalitogenic protein, suprasegmental levels of nervous system, Neurodegenerative Disorder, RA - Rheumatoid arthritis, atrophic arthritis, Degenerative Neurologic Disease, AD - Alzheimer's disease, Alzheimer Type Dementia, MBPD, Neurologic Degenerative Disease, Pregnancy-associated major basic protein, ALZHEIMER DIS EARLY ONSET, Parkinson syndrome, Presenile, Myelin Sheaths, Alzheimers disease, Rheumatoid, Parkinson's syndrome, Scleroses, Senile, Parkinsons, Alzheimer disease, suprasegmental structures, vimentin, Acute Confusional Senile Dementia, type III intermediate filament associated protein, familial, Alzheimer's Dementia, Alzheimer Type, mld, Immunodeficiency and Immunosuppression Disorders, peripherin, C76307, Diseases, AI836096, tissue portion, NOS, simple tissue, shi, Hmbpr, Peptidylarginine Deimination, astrocyte sheath, Dementia, immune system disorder, Alzheimers, PTM, Degenerative Diseases, Alzheimer, susceptibility to, Encephalon, Protein Deimination, Sheaths, Dementias, EMBP, Neurologic Disease, immune dysfunction, Senile Dementia, Patient, Degenerative, paralysis agitans, post-translational modification, Rheumatoid arthritis (disorder), Alzheimer's Disease, Myelin A1 protein, IMMUNE MECHANISM DIS NEC, Disorder of the immune mechanism NOS, Dementia of the Alzheimer's type, the brain, R75289, AUTOIMMUNE DISEASE NEC, Autoimmune Disease, Degenerative Neurologic Disorders, Gene, protein-containing complex, Focal Onset, Protein-Arginine Deimination, Rheumatic gout, unspecified (disorder), ALZHEIMER DIS, COLEC1, polypeptide chain, [X]Dementia in Alzheimer's disease, rheumatoid arthritis, Gene Products, IMMUNE MECHANISM DIS NOS, atrophic Arthritis, arthritis or polyarthritis, Nervous System, presenile and senile dementia, Other deficiency of cell-mediated immunity, FOCUS, Chronic rheumatic arthritis, Disorders involving the immune mechanism, Rheumatoid arthritis NOS (disorder), Protein Arginine Deimination, Proteoglycan 2, MBL, posttranslational protein modification, MBP, immune disorder, Neurodegenerative Disorders, Idiopathic PD, FOCAL ONSET ALZHEIMERS DIS, Neurologic, Neurologic Degenerative Diseases, desmin, Clients, Alzheimer Disease, Degenerative Neurologic Diseases, GFAP, progression of, Spinal Cord, Alzheimer's disease (disorder), Alzheimers Dementia, Alzheimers dementia, medullary sheath, Alzheimer Senile Dementia, Disease, Neurologic Disorder, protein complex, not elsewhere classified, Sheath, Deimination, Proteins, encephalon, Client, Alzheimer dementia, BMPG, disease or disorder of immune system, Primary Senile Degenerative Dementia, Degenerative Neurologic Disorder, [X]Dementia in Alzheimer's disease (disorder), native protein, natural protein, autoimmune arthritis, Protein, arthritis, MBL2D, Disorder of the immune mechanism NOS (disorder), Proliferative arthritis, immune system disease or disorder, Degenerative Conditions, IMMUNDEF T-CELL DEF NOS, Dementia in Alzheimer's disease, Alzheimer's Disease Pathway, Neurologic Degenerative Conditions, disease of immune system, golli-mbp, Alzheimer Dementia, disorder of immune system, post-translational amino acid modification, autoimmune diseases, Protein Gene Products, Parkinsonian disorder, immune disease, Gene Proteins, Rheumatoid Arthritis, Schwann cell myelin sheath, Myelin, Late Onset, Parkinson's disease NOS (disorder), Dementia in Alzheimer's disease (disorder), Other specified disorders of the immune mechanism, Neurodegenerative Disease, Central Nervous System, Immunodeficiency with predominant T-cell defectForms, Antigenic Determinants, type 2, posttranslational modification, Unspecified disorder of immune mechanism, insular sclerosis, MBP-C, FON1, Addresses, Rheumatoid arthritis NOS, FLORAL ORGAN NUMBER 1, Long Term, Other specified disorders of the immune mechanism (disorder), Rheumatoid disease, CNS tracts and commissures, Polypeptides, RhA - Rheumatoid arthritis, protein polypeptide chains, unspecified, M(3L)i, Other specified disorders involving the immune mechanism, "Multiple sclerosis" EXACT [SNOMEDCT_2005_07_31:155023009], cerebral spinal fluid, Citrulline, responsivity, Ly-4, 2, adenomas, Eosinophil granule major basic protein, posttranslational amino acid modification, (S)-2-amino-5-guanidinopentanoic acid, L-methionine aminopeptidase activity, Autoimmune disease, Arthritis, M, rheumatoid, citrulina, Tissue, Bdr, R, Arginine, Bodily, Monohydrate DL-Arginine Acetate, proteins, Myelin membrane encephalitogenic protein, number of, suprasegmental levels of nervous system, SNAP-25, Secretion, scientific observation, white substance, Secretions, D9, M(3)RpS17, Disseminated Sclerosis, Epitope, suprasegmental structures, vimentin, L-Ornithine, MYH-associated polyposis, Longterm Effect, arginine, Myelin Basic Protein, 20.2 kDa Isoform, exocrine gland fluid/secretion, Bodily Secretion, Immunodeficiency and Immunosuppression Disorders, M(3)i(55), Golli MBP1 Protein, Cit, leucocyte mediated immunity, GENA70, secretion, simple tissue, shi, glial fibrillary acidic protein, Antigenic Determinant, MUTYH-associated polyposis, rpS17, MUTYH-related AFAP, deep, RUTBC3, immune system disorder, LAMB2T, HOG7 Protein, Sheaths, "insular sclerosis" EXACT [CSP2005:2042-2324], CD4mut, T lymphocyte mediated immunity, T-lymphocyte, Cerebro, human, substantia alba, Multiple, T cell, Matters, Rheumatoid arthritis (disorder), multiple colorectal, N(5)-carbamoyl-DL-ornithine, MUTYH-related attenuated familial polyposis coli, White, exocrine gland secretion, Disorder of the immune mechanism NOS, FLORAL DEFECTIVE 10, "multiple sclerosis" EXACT [NCI2004_11_17:C3243], CSF2, Peptidomics, Effects, Sclerosis, R75289, Multiple Sclerosis, number, GM-CSF, SUPERMAN, Antigenic Specificity, protein-containing complex, Rheumatic gout, Protein-Arginine Deimination, unspecified (disorder), period, IFNA13, Determinant, M(3)i, Gene Products, Cerebro Spinal, "Multiple sclerosis" EXACT [ICD9CM_2006:340], arthritis or polyarthritis, MAP, "Multiple sclerosis (disorder)" EXACT [SNOMEDCT_2005_07_31:24700007], "Multiple sclerosis NOS (disorder)" EXACT [SNOMEDCT_2005_07_31:192930001], Chronic rheumatic arthritis, Longterm, MBP4 Protein, Disorders involving the immune mechanism, Rheumatoid arthritis NOS (disorder), familial adenomatous polyposis 2, immune cell mediated immunity, Protein Arginine Deimination, Proteoglycan 2, inflammation, MBL, Long-Term, l(3)dtOA4, MBP, man, study assay, Isoform 7, sargramostim, N5-(aminocarbonyl)-, desmin, bodily secretion, CNS white matter, mature T cell, GFAP, M(3)i[55], L-Arg, peptidos, progression of, immune cell effector process, Golli-MBP1 Protein, cellular immune response, measuring, Proteins, Fluids, MBP3 Protein, spinal fluid, Synaptosomal-associated 25 kDa protein, MS (Multiple Sclerosis), L-Isomer, encephalon, Spinal Fluid, disease or disorder of immune system, Isoform 5, Isoform 6, polypeptide, Isoform 3, Spinal Fluids, Isoform 4, Isoform 1, Isoform 2, MS, Fluid, native protein, L-Isomer Arginine, Cerebellar White, T-cell differentiation antigen L3T4, autoimmune arthritis, MUTYH-related attenuated FAP, Long Term Effects, chemical analysis, 2-Amino-5-uredovaleric acid, BcDNA:RE44119, MBL2D, Disorder of the immune mechanism NOS (disorder), CNS tract/commissure, IMMUNDEF T-CELL DEF NOS, (2S)-2-amino-5-guanidinopentanoic acid, M(3)q, Specificity, CSF, disease of immune system, Disseminated, anon-EST:Posey48, disorder of immune system, post-translational amino acid modification, Longterm Effects, immune disease, Gene Proteins, Myelin, LAMNB2, M(3L)i[55], MAP syndrome, Immunodeficiency with predominant T-cell defect, Rps17, Golli-MBP2 Protein, neuronal white matter, T-cell surface antigen T4/Leu-3, 17.2 kDa Isoform, methionine aminopeptidase activity, determination, L-arginine, DL-Arginine Acetate, MBP1, RPS17, Matter, Monohydrate, protein, 2-amino-5-(carbamoylamino)pentanoic acid, peptide, White Matter, M(3)67, B2T, L3T4, peptido, RA, SUP, white matter of neuraxis, liquor cerebrospinalis, synganglion, leucocyte immune effector process, Arthritis or polyarthritis, Arg, protein aggregate, Autoimmune, Effect, immature T cell, peptidase M activity, HSMBPC, portion of tissue, DEFIC CELL IMMUNITY NOS, rabGAPLP, Immune Processes, Immune Responses, simple tissue., Deficiency of cell-mediated immunity, inflammatory response, peptides, rheumatic, reference sample, [X]Disorder involving the immune mechanism, l(3)67BDo, (S)-2-Amino-5-guanidinovaleric acid, Immune System and Related Disorders, molgramostin, min, RabGAP-5, Super protein, sp, HOG5 Protein, Cerebellar White Matter, RA - Rheumatoid arthritis, Golli MBP2 Protein, Immune, atrophic arthritis, RUSC3, MBPD, Pregnancy-associated major basic protein, Myelin Sheaths, Long-Term Effects, L-Arginin, Rheumatoid, Cerebro Spinal Fluid, Process, MOD_RES Citrulline, T-cell surface antigen T4|Leu-3, white mater, type III intermediate filament associated protein, external secretion, Arginine Hydrochloride, autosomal recessive familial adenomatous polyposis, M(3)67C, Maps, IFNA@, extra or missing physical or functional parts, Cerebro Spinal Fluids, any method, mld, leukocyte immune effector process, 18.5 kDa Isoform, peripherin, C76307, Diseases, AI836096, tissue portion, "Generalized multiple sclerosis (disorder)" EXACT [SNOMEDCT_2005_07_31:192928003], Hmbpr, DL-2-amino-5-ureidovaleric acid, Peptidylarginine Deimination, Cerebellar, autosomal recessive, L-Arginine, T-cell, PTM, T-cell surface glycoprotein CD4, IFL, susceptibility to, Encephalon, White Matters, IFN, Rp S17, MBP2 Protein, Protein Deimination, EMBP, Colony-stimulating factor, Csfgm, RABGAP5, immune dysfunction, Cerebellar White Matters, Patient, post-translational modification, dl-citrulline, Polypeptide, Myelin A1 protein, IMMUNE MECHANISM DIS NEC, time, Proteomes, cell-mediated immunity, IFN-ALPHA, the brain, human being, exocrine gland fluid, exocrine gland fluid or secretion, AUTOIMMUNE DISEASE NEC, infiltrating, Autoimmune Disease, L Isomer, Gene, T-cell mediated immunity, MBP1 Protein, L-(+)-arginine, Cerebrospinal, COLEC1, M(3)S33, (2S)-2-amino-5-(carbamimidamido)pentanoic acid, polypeptide chain, rheumatoid arthritis, colony-stimulating factor, IMMUNE MECHANISM DIS NOS, atrophic Arthritis, GMCSF, familial adenomatous polyposis, reactivity, Other deficiency of cell-mediated immunity, IFN-alphaD, T-lymphocyte mediated immunity, BM600, cell-mediated immune response, N(5)-carbamoylornithine, white matter, Antigenic, Minute, Citrullin, posttranslational protein modification, immune disorder, EBR2, autosomal recessive multiple colorectal adenomas, Mif1, secreted substance, Molgramostin, Immune Response, generalised multiple sclerosis, DmelCG3922, Clients, has or lacks parts of type, N(5)-(aminocarbonyl)-DL-ornithine, Long-Term Effect, generalized multiple sclerosis, Immune Process, Controlled, MUTYH-related attenuated familial adenomatous polyposis, Disease, data, Controlling, MUTYH-Associated Polyposis, protein complex, not elsewhere classified, Sheath, EBR2A, Deimination, total expressed protein, Cerebrospinal Fluids, DL Arginine Acetate, Client, Peptide, BMPG, mereological quality, natural protein, Sargramostim, Protein, Hydrochloride, arthritis, L Arginine, rare (European definition), Determinants, T lymphocyte, Proliferative arthritis, citrulline, immune system disease or disorder, FLO10, MYH-Associated Polyposis, golli-mbp, HERP, Acute Fulminating, CG3922, autoimmune diseases, Protein Gene Products, Rheumatoid Arthritis, N(5)-(aminocarbonyl)ornithine, cardinality, Response, Other specified disorders of the immune mechanism, CD4, Peptid, assay, response, FAP2, 21.5 kDa Isoform, colorectal adenomatous polyposisthe brain, liquid chromatography tandem mass spectroscopy, LC-MS2, "multiple sclerosis" EXACT [NCI2004_11_17:C3243], Cerebro Spinal Fluid, Disseminated Sclerosis, suprasegmental structures, human being, insular sclerosis, T-cell surface antigen T4/Leu-3, T-cell surface antigen T4|Leu-3, Sclerosis, Deimination, Multiple Sclerosis, LC-MS/MS, Fluids, Cerebrospinal Fluids, spinal fluid, MS (Multiple Sclerosis), encephalon, Protein-Arginine Deimination, Cell, Spinal Fluid, LC-MS-MS, Cerebrospinal, Cerebro Spinal Fluids, Spinal Fluids, L3T4, LC/MS/MS, MS, "Multiple sclerosis" EXACT [SNOMEDCT_2005_07_31:155023009], Fluid, cerebral spinal fluid, T-cell differentiation antigen L3T4, responsivity, LC-MSMS, Protein, Ly-4, Cerebro Spinal, liquor cerebrospinalis, "Generalized multiple sclerosis (disorder)" EXACT [SNOMEDCT_2005_07_31:192928003], synganglion, Peptidylarginine Deimination, immature T cell, T lymphocyte, "Multiple sclerosis (disorder)" EXACT [SNOMEDCT_2005_07_31:24700007], reactivity, "Multiple sclerosis NOS (disorder)" EXACT [SNOMEDCT_2005_07_31:192930001], T-cell, LCMSMS, T-cell surface glycoprotein CD4, Encephalon, Protein Arginine Deimination, Protein Deimination, CD4mut, "insular sclerosis" EXACT [CSP2005:2042-2324], CSF, suprasegmental levels of nervous system, T-lymphocyte, Cerebro, man, Disseminated, human, Acute Fulminating, Multiple, T cell, generalised multiple sclerosis, liquid chromatography-tandem mass spectroscopy, mature T cell, liquid chromatography tandem mass spectrometry, CD4, response, generalized multiple sclerosis, "Multiple sclerosis" EXACT [ICD9CM_2006:340].falseHuman brain LC-MS/MS - Brain Citrullination Patterns and T Cell Reactivity of Cerebrospinal Fluid-Derived CD4+ T Cells in Multiple SclerosisCitrullination as a post-translational modification has been described in a couple of autoimmune diseases like rheumatoid arthritis (RA) and multiples sclerosis (MS). We investigated citrullination brain tissue from MS patients and healthy individuals (HD). The myelin sheath proteins have been the focus of citrullination and neurodegenerative diseases like Alzheimers Disease (AD), Parkinsons and MS. We analysed whole brain tissue of MS patients and HD and established a catalogue of citrullinated proteins. Besides new citrullinated proteins we found additional citrullinated sites on the already described proteins: MBP, GFAP and Vimentin.2019-04-102017-12-01PXD0083442806551646099180498295358511145284218809058113633363515242602758385NCBITaxon:128068888561896111430118726355557114526236493461327467073853883641135461582158236889547627211232944222911809923233654583334607925193659143205971293865581914932637371250232NCBITaxon:12721119577481866584345135867221755437408169180454266834453058612668351498225058149636745855452811320810039237514636942049433208964208963445974137979128384400667935293671521659940483216597216595455013152826930421659156271616968332183217292042779447623764543172030949801975255569781439843948840479NCBITaxon:215752533855153105106743989903712285775951520596876234555588845587077918178081736309431794571698936160488409859NCBITaxon:3716210478267940150590714836432042106132049138169363035554320466326334565453511025411103217459216129410026420369456941016763410210761277351131658239254727933428146135843017463345774449167547604893267568403019172651813019411192943936711041131023932025559863258278839659104759347495165299835525663175854310243260866310245980875741755518320196447145268045796190832331156114155421932555217634123598755529NCBITaxon:47518502547611361574146547718006655648433767729976798251021699823897641373511557444474153NCBITaxon:505578996984410003646534933414754801946751299114359741276473137086326547876569835322159983819201198524794640986099586766859919157295137221171101107687834974198601488406334249235985988655974649987039202111072943311711397215987419085037117082841823502414511391902197822474636046147123743759392532566489050794526591972211915853101774208588596NCBITaxon:61575052102830798951105198997237505957613172000263419610264940772275689964975157244NCBITaxon:22023717NCBITaxon:1703612857050617476792745062724915961538400524643213686150596866629417347515363291018194301086731018557303963558633149286287132161865368595105135260710185687294296110091416333NCBITaxon:619184023210007348824187878645159812863577553470951451225786260704260705260707658457405416561007133705654195NCBITaxon:3055504457913998781681928752829126806315327341478281055524NCBITaxon:9606469008150251930283672859300852NCBITaxon:56938268830640179469915101515482428381113704759272370828167728503515819901195195326738637024924053608862248881756261583558371533376057267119350199808611935021678793711371272407371457125627457903113335503728142433747924910078711082NCBITaxon:961559463318586260799141262200298492670NCBITaxon:12637192812492125283038568385695911100658123756127504542666255151978837503600941293497905435247214012576499085151514389923745374744544641524323592887051580595536157932716029385114978633892894535936479437NCBITaxon:6854412754225117159010901341673871589552101296610306129671585158451584937659393432715910022637673388942345128768914647929365761642803421641331599280382803536909108917689462181214108034817939228788929502711311749346819227321890382107601247190400727114311402064119810871355477436581424507229533796982042321291632180334708714537209164573315754699287770202060328114319338293550833291292211487252649997283035727550717629970767892683704152140532941281607839563924227377596207325516936053307972551811354915974953502611595561432138406072587814144733491949634016143347316461046603815184547448500356709747751240174841833572042746076994688103762014887289093164358500713894649408941442423277422140921157781154756929793244704749906604162103591905158749907312989913112273170187103589915NCBITaxon:372961036098334113079813367953164072994671034015786303337330638301130641399253064236365059547883431710337299404458620734011535711195296526111147161338654131316634305521323120179935129938505731631764261979401151345844577267872862321933486211607913922279835168119612552281167617573121080772134879999488618140843410335199632184961392488209633043937586266447NCBITaxon:2697049339862436941103121958832050920290610997586448643249952529724634389427863789426256737863912334355141998349317998686554055343529148654514712454661042986357124679151641358884019373345087718238039129529719748693102868899951337310548771251632138985076255470119380625631886571303443516558658862238NCBITaxon:44664946454636493NCBITaxon:110711428006288356491845881087439145943854331116781077854314408043933495346939773821899318226900351281459533996686959541869420030895448697244366206656395453005586233551804264308692200302284812426428150475149910510299414452386262903512089557117008930621864419306157558413101653823525577223994636010636010439947544404237610212790568813377518236116229629817677187093128110502382451855796694654318632051824097441739412450128853183889198853191113782559103716473516601261557NCBITaxon:101142845031631198573859523343237956026087121346395984275295952664373343232235443142752422430814336195931334565943274169963112223360520121697952528386972864368012187073347472790104081882976038181249885340188439733127441416395888587252029554648038343691224326408172124193559552128161405592042546551945822886091838271274423408170193329829721274420127442694328413996166018762548296471876247480119915095648188229725431480154120455138473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