{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:57:56Z","timestamp":1787003876138,"version":"build-2736575974"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,1,5]],"date-time":"2017-01-05T00:00:00Z","timestamp":1483574400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,1,5]],"date-time":"2017-01-05T00:00:00Z","timestamp":1483574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Common variable immunodeficiency (CVID) is a heterogeneous group of diseases. Our aim was to define sub-groups of CVID patients with similar phenotypes and clinical characteristics. Using eight-color flow cytometry, we analyzed both B- and T-cell phenotypes in a cohort of 88 CVID patients and 48 healthy donors. A hierarchical clustering of probability binning \u201cbins\u201d yielded a separate cluster of 22 CVID patients with an abnormal phenotype. We showed coordinated proportional changes in na\u00efve CD4+ T-cells (decreased), intermediate CD27\u2212\u2009CD28+ CD4+ T-cells (increased) and CD21low B-cells (increased) that were stable for over three years. Moreover, the lymphocytes\u2019 immunophenotype in this patient cluster exhibited features of profound immunosenescence and chronic activation. Thrombocytopenia was only found in this cluster (36% of cases, manifested as Immune Thrombocytopenia (ITP) or Evans syndrome). Clinical complications more frequently found in these patients include lung fibrosis (in 59% of cases) and bronchiectasis (55%). The degree of severity of these symptoms corresponded to more deviation from normal levels with respect to CD21low B-cells, na\u00efve CD4+ and CD27\u2212\u2009CD28+ CD4+ T-cells. Next-generation sequencing did not reveal any common genetic background. We delineate a subgroup of CVID patients with activated and immunosenescent immunophenotype of lymphocytes and distinct set of clinical complications without common genetic background.<\/jats:p>","DOI":"10.1038\/srep39710","type":"journal-article","created":{"date-parts":[[2017,1,5]],"date-time":"2017-01-05T05:35:34Z","timestamp":1483594534000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Common Variable Immunodeficiency patients with a phenotypic profile of immunosenescence present with thrombocytopenia"],"prefix":"10.1038","volume":"7","author":[{"given":"Jan","family":"Stuchl\u00fd","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Kanderov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Vlkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"He\u0159manov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Sl\u00e1mov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ond\u0159ej","family":"Pel\u00e1k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Taraldsrud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalibor","family":"J\u00edlek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavl\u00edna","family":"Kr\u00e1l\u00ed\u010dkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00f8rre","family":"Fevang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Trkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ond\u0159ej","family":"Hru\u0161\u00e1k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Fro\u0148kov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"\u0160ediv\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u0159\u00ed","family":"Litzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"Kalina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,5]]},"reference":[{"key":"BFsrep39710_CR1","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1182\/blood-2011-09-377945","volume":"119","author":"ES Resnick","year":"2012","unstructured":"Resnick, E. S., Moshier, E. L., Godbold, J. H. & Cunningham-Rundles, C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood 119, 1650\u20131657 (2012).","journal-title":"Blood"},{"issue":"1","key":"BFsrep39710_CR2","first-page":"116-126.e11","volume":"134","author":"Benjamin Gathmann","year":"2014","unstructured":"Gathmann, B. et al. Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J. Allergy Clin. Immunol. 134, 116\u2013126.e11 (2014).","journal-title":"Journal of Allergy and Clinical Immunology"},{"key":"BFsrep39710_CR3","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1023\/A:1025373601374","volume":"23","author":"B Piqueras","year":"2003","unstructured":"Piqueras, B. et al. Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J. Clin. Immunol. 23, 385\u2013400 (2003).","journal-title":"J. Clin. Immunol"},{"key":"BFsrep39710_CR4","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1182\/blood.V99.5.1544","volume":"99","author":"K Warnatz","year":"2002","unstructured":"Warnatz, K. et al. Severe deficiency of switched memory B cells (CD27+IgM-IgD-) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood 99, 1544\u20131551 (2002).","journal-title":"Blood"},{"key":"BFsrep39710_CR5","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1182\/blood-2007-06-091744","volume":"111","author":"C Wehr","year":"2008","unstructured":"Wehr, C. et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood 111, 77\u201385 (2008).","journal-title":"Blood"},{"key":"BFsrep39710_CR6","doi-asserted-by":"crossref","first-page":"6814","DOI":"10.1182\/blood-2011-06-361881","volume":"118","author":"GJ Driessen","year":"2011","unstructured":"Driessen, G. J. et al. B-cell replication history and somatic hypermutation status identify distinct pathophysiologic backgrounds in common variable immunodeficiency. Blood 118, 6814\u201323 (2011).","journal-title":"Blood"},{"key":"BFsrep39710_CR7","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1182\/blood.V87.2.674.bloodjournal872674","volume":"87","author":"P Aukrust","year":"1996","unstructured":"Aukrust, P. et al. Persistent activation of the tumor necrosis factor system in a subgroup of patients with common variable immunodeficiency\u2013possible immunologic and clinical consequences. Blood 87, 674\u201381 (1996).","journal-title":"Blood"},{"key":"BFsrep39710_CR8","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.4049\/jimmunol.178.6.3932","volume":"178","author":"A Giovannetti","year":"2007","unstructured":"Giovannetti, A. et al. Unravelling the complexity of T cell abnormalities in common variable immunodeficiency. J. Immunol. 178, 3932\u201343 (2007).","journal-title":"J. Immunol."},{"key":"BFsrep39710_CR9","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/j.1365-2249.2006.02999.x","volume":"143","author":"M Vlkov\u00e1","year":"2006","unstructured":"Vlkov\u00e1, M. et al. Age dependency and mutual relations in T and B lymphocyte abnormalities in common variable immunodeficiency patients. Clin. Exp. Immunol. 143, 373\u20139 (2006).","journal-title":"Clin. Exp. Immunol."},{"key":"BFsrep39710_CR10","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1007\/s10875-010-9424-3","volume":"30","author":"G Mouillot","year":"2010","unstructured":"Mouillot, G. et al. B-cell and T-cell phenotypes in CVID patients correlate with the clinical phenotype of the disease. J. Clin. Immunol. 30, 746\u201355 (2010).","journal-title":"J. Clin. Immunol."},{"key":"BFsrep39710_CR11","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/cyto.b.20432","volume":"74","author":"K Warnatz","year":"2008","unstructured":"Warnatz, K. & Schlesier, M. Flowcytometric phenotyping of common variable immunodeficiency. Cytometry B. Clin. Cytom. 74, 261\u201371 (2008).","journal-title":"Cytometry B. Clin. Cytom"},{"key":"BFsrep39710_CR12","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.clim.2015.06.013","volume":"160","author":"M Vlkova","year":"2015","unstructured":"Vlkova, M. et al. Regulatory B cells in CVID patients fail to suppress multifunctional IFN-\u03b3+ TNF-\u03b1+CD4+ T cells differentiation. Clin. Immunol. 160, 292\u2013300 (2015).","journal-title":"Clin. Immunol."},{"key":"BFsrep39710_CR13","doi-asserted-by":"crossref","first-page":"13451","DOI":"10.1073\/pnas.0901984106","volume":"106","author":"M Rakhmanov","year":"2009","unstructured":"Rakhmanov, M. et al. Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells. Proc. Natl. Acad. Sci. USA 106, 13451\u20136 (2009).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"11","key":"BFsrep39710_CR14","doi-asserted-by":"crossref","first-page":"6431","DOI":"10.4049\/jimmunol.0903876","volume":"185","author":"Marcela Vlkov\u00e1","year":"2010","unstructured":"Vlkov\u00e1, M. et al. Characterization of lymphocyte subsets in patients with common variable immunodeficiency reveals subsets of naive human B cells marked by CD24 expression. J. Immunol. 185, 6431\u20138 (2010).","journal-title":"The Journal of Immunology"},{"key":"BFsrep39710_CR15","doi-asserted-by":"crossref","first-page":"5026","DOI":"10.1182\/blood-2009-09-243071","volume":"115","author":"I Isnardi","year":"2010","unstructured":"Isnardi, I. et al. Complement receptor 2\/CD21- human naive B cells contain mostly autoreactive unresponsive clones. Blood 115, 5026\u201336 (2010).","journal-title":"Blood"},{"key":"BFsrep39710_CR16","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1002\/art.37828","volume":"65","author":"D Saadoun","year":"2013","unstructured":"Saadoun, D. et al. Expansion of autoreactive unresponsive CD21-\/low B cells in sj\u00f6gren\u2019s syndrome-associated lymphoproliferation. Arthritis Rheum. 65, 1085\u20131096 (2013).","journal-title":"Arthritis Rheum."},{"key":"BFsrep39710_CR17","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1078\/0171-2985-00198","volume":"206","author":"K Warnatz","year":"2002","unstructured":"Warnatz, K. et al. Expansion of CD19(hi)CD21(lo\/neg) B cells in common variable immunodeficiency (CVID) patients with autoimmune cytopenia. Immunobiology 206, 502\u201313 (2002).","journal-title":"Immunobiology"},{"key":"BFsrep39710_CR18","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1002\/cyto.a.20801","volume":"75","author":"T Kalina","year":"2009","unstructured":"Kalina, T. et al. Profiling of polychromatic flow cytometry data on B-cells reveals patients\u2019 clusters in common variable immunodeficiency. Cytometry 75, 902\u20139 (2009).","journal-title":"Cytometry"},{"key":"BFsrep39710_CR19","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/j.1365-2249.2006.03314.x","volume":"147","author":"B Fevang","year":"2007","unstructured":"Fevang, B. et al. Low numbers of regulatory T cells in common variable immunodeficiency: Association with chronic inflammation in vivo . Clin. Exp. Immunol. 147, 521\u2013525 (2007).","journal-title":"Clin. Exp. Immunol"},{"key":"BFsrep39710_CR20","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1006\/clim.1999.4799","volume":"93","author":"ME Conley","year":"1999","unstructured":"Conley, M. E., Notarangelo, L. D. & Etzioni, A. Diagnostic Criteria for Primary Immunodeficiencies. Clin. Immunol. 93, 190\u2013197 (1999).","journal-title":"Clin. Immunol."},{"key":"BFsrep39710_CR21","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","volume":"43","author":"MA DePristo","year":"2011","unstructured":"DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491\u2013498 (2011).","journal-title":"Nat. Genet."},{"key":"BFsrep39710_CR22","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754\u20131760 (2009).","journal-title":"Bioinformatics"},{"key":"BFsrep39710_CR23","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/nprot.2009.86","volume":"4","author":"P Kumar","year":"2009","unstructured":"Kumar, P., Henikoff, S. & Ng, P. C. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat. Protoc. 4, 1073\u201381 (2009).","journal-title":"Nat. Protoc."},{"key":"BFsrep39710_CR24","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","volume":"7","author":"IA Adzhubei","year":"2010","unstructured":"Adzhubei, I. A. et al. A method and server for predicting damaging missense mutations. Nat. Methods 7, 248\u20139 (2010).","journal-title":"Nat. Methods"},{"key":"BFsrep39710_CR25","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/bib\/bbs017","volume":"14","author":"H Thorvaldsd\u00f3ttir","year":"2013","unstructured":"Thorvaldsd\u00f3ttir, H., Robinson, J. T. & Mesirov, J. P. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief. Bioinform. 14, 178\u201392 (2013).","journal-title":"Brief. Bioinform."},{"key":"BFsrep39710_CR26","doi-asserted-by":"crossref","first-page":"e1003806","DOI":"10.1371\/journal.pcbi.1003806","volume":"10","author":"G Finak","year":"2014","unstructured":"Finak, G. et al. OpenCyto: an open source infrastructure for scalable, robust, reproducible, and automated, end-to-end flow cytometry data analysis. PLoS Comput. Biol. 10, e1003806 (2014).","journal-title":"PLoS Comput. Biol."},{"key":"BFsrep39710_CR27","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/cyto.a.22431","volume":"85","author":"J Stuchl\u00fd","year":"2014","unstructured":"Stuchl\u00fd, J. & Kalina, T. Analyses of large flow cytometry datasets. Cytom. Part A 85, 203\u20135 (2014).","journal-title":"Cytom. Part A"},{"key":"BFsrep39710_CR28","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/1097-0320(20010901)45:1<47::AID-CYTO1143>3.0.CO;2-A","volume":"45","author":"M Roederer","year":"2001","unstructured":"Roederer, M., Moore, W., Treister, A., Hardy, R. R. & Herzenberg, L. A. Probability binning comparison: a metric for quantitating multivariate distribution differences. Cytometry 45, 47\u201355 (2001).","journal-title":"Cytometry"},{"key":"BFsrep39710_CR29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2009\/193947","volume":"2009","author":"WT Rogers","year":"2009","unstructured":"Rogers, W. T. & Holyst, H. A. FlowFP: A Bioconductor Package for Fingerprinting Flow Cytometric Data. Adv. Bioinformatics 2009, 1\u201311 (2009).","journal-title":"Adv. Bioinformatics"},{"key":"BFsrep39710_CR30","unstructured":"Pollard, K. S., Dudoit, S. & van der Laan, M. J. In Bioinforma. Comput. Biol. Solut. Using R Bioconductor ( Gentleman, R., Carey, V., Huber, W., Irizarry, R. & D., S. ) 251\u2013272 (Springer, 2005)."},{"key":"BFsrep39710_CR31","first-page":"104","volume":"111","author":"JA Sosman","year":"2000","unstructured":"Sosman, J. A. et al. Interleukin 10-induced thrombocytopenia in normal healthy adult volunteers: Evidence for decreased platelet production. Br. J. Haematol. 111, 104\u2013111 (2000).","journal-title":"Br. J. Haematol"},{"key":"BFsrep39710_CR32","doi-asserted-by":"crossref","unstructured":"Pel\u00e1k, O. et al. Appearance of CMV specific T-cells predicts fast resolution of viremia post hematopoietic Stem cell transplantation. Cytometry B. Clin. Cytom. doi: 10.1002\/cyto.b.21348 (2015).","DOI":"10.1002\/cyto.b.21348"},{"key":"BFsrep39710_CR33","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/bmt.2010.261","volume":"46","author":"L Kr\u00f3l","year":"2011","unstructured":"Kr\u00f3l, L. et al. Signature profiles of CMV-specific T-cells in patients with CMV reactivation after hematopoietic SCT. Bone Marrow Transplant. 46, 1089\u201398 (2011).","journal-title":"Bone Marrow Transplant"},{"key":"BFsrep39710_CR34","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.humimm.2012.07.342","volume":"73","author":"T Freiberger","year":"2012","unstructured":"Freiberger, T. et al. Sequence variants of the TNFRSF13B gene in Czech CVID and IgAD patients in the context of other populations. Hum. Immunol. 73, 1147\u201354 (2012).","journal-title":"Hum. Immunol."},{"key":"BFsrep39710_CR35","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1365-2249.2008.03863.x","volume":"156","author":"AEJ Poodt","year":"2009","unstructured":"Poodt, A. E. J. et al. TACI mutations and disease susceptibility in patients with common variable immunodeficiency. Clin. Exp. Immunol. 156, 35\u201339 (2009).","journal-title":"Clin. Exp. Immunol."},{"key":"BFsrep39710_CR36","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.jaci.2012.11.054","volume":"131","author":"G Uzel","year":"2013","unstructured":"Uzel, G. et al. Dominant gain-of-function STAT1 mutations in FOXP3 wild-type immune dysregulation-polyendocrinopathy-enteropathy-X-linked-like syndrome. J. Allergy Clin. Immunol. 131, 1611\u201323 (2013).","journal-title":"J. Allergy Clin. Immunol."},{"key":"BFsrep39710_CR37","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.clim.2004.05.010","volume":"113","author":"C Wehr","year":"2004","unstructured":"Wehr, C. et al. A new CD21 low B cell population in the peripheral blood of patients with SLE. Clin. Immunol. 113, 161\u2013171 (2004).","journal-title":"Clin. Immunol."},{"key":"BFsrep39710_CR38","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1093\/intimm\/dxn075","volume":"20","author":"R Okada","year":"2008","unstructured":"Okada, R., Kondo, T., Matsuki, F., Takata, H. & Takiguchi, M. Phenotypic classification of human CD4+ T cell subsets and their differentiation. Int. Immunol. 20, 1189\u201399 (2008).","journal-title":"Int. Immunol."},{"key":"BFsrep39710_CR39","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.smim.2004.02.007","volume":"16","author":"V Appay","year":"2004","unstructured":"Appay, V. & Rowland-Jones, S. L. Lessons from the study of T-cell differentiation in persistent human virus infection. Semin. Immunol. 16, 205\u201312 (2004).","journal-title":"Semin. Immunol."},{"key":"BFsrep39710_CR40","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.4049\/jimmunol.179.4.2609","volume":"179","author":"W Lee","year":"2007","unstructured":"Lee, W., Yang, Z., Li, G., Weyand, C. M. & Goronzy, J. J. Unchecked CD70 expression on T cells lowers threshold for T cell activation in rheumatoid arthritis. J. Immunol. 179, 2609\u201315 (2007).","journal-title":"J. Immunol."},{"key":"BFsrep39710_CR41","doi-asserted-by":"crossref","first-page":"6442","DOI":"10.4049\/jimmunol.0901565","volume":"183","author":"CRL Beishuizen","year":"2009","unstructured":"Beishuizen, C. R. L. et al. Chronic CD70-driven costimulation impairs IgG responses by instructing T cells to inhibit germinal center B cell formation through FasL-Fas interactions. J. Immunol. 183, 6442\u201351 (2009).","journal-title":"J. Immunol."},{"key":"BFsrep39710_CR42","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/ni869","volume":"4","author":"K Tesselaar","year":"2003","unstructured":"Tesselaar, K. et al. Lethal T cell immunodeficiency induced by chronic costimulation via CD27\u2013CD70 interactions. Nat. Immunol. 4, 49\u201354 (2003).","journal-title":"Nat. Immunol."},{"key":"BFsrep39710_CR43","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.cell.2012.02.045","volume":"148","author":"E Pujadas","year":"2012","unstructured":"Pujadas, E. & Feinberg, A. P. Regulated noise in the epigenetic landscape of development and disease. Cell 148, 1123\u20131131 (2012).","journal-title":"Cell"},{"key":"BFsrep39710_CR44","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1111\/j.1532-5415.2010.02965.x","volume":"58","author":"TM Lindstrom","year":"2010","unstructured":"Lindstrom, T. M. & Robinson, W. H. Rheumatoid Arthritis: A Role for Immunosenescence? J. Am. Geriatr. Soc. 58, 1565\u20131575 (2010).","journal-title":"J. Am. Geriatr. Soc"},{"key":"BFsrep39710_CR45","doi-asserted-by":"crossref","first-page":"4190","DOI":"10.1182\/blood-2010-08-302984","volume":"117","author":"C Neunert","year":"2011","unstructured":"Neunert, C. et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 117, 4190\u2013207 (2011).","journal-title":"Blood"},{"key":"BFsrep39710_CR46","doi-asserted-by":"crossref","unstructured":"Rodeghiero, F. et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children : report from an international working group Standardization of terminology, definitions and outcome criteria in immune thrombocyt. 113, 2386\u20132393 (2014).","DOI":"10.1182\/blood-2008-07-162503"},{"key":"BFsrep39710_CR47","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.autrev.2014.01.026","volume":"13","author":"E Lo","year":"2014","unstructured":"Lo, E. & Deane, S. Diagnosis and classification of immune-mediated thrombocytopenia. Autoimmun. Rev. 13, 577\u2013583 (2014).","journal-title":"Autoimmun. Rev."},{"key":"BFsrep39710_CR48","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1007\/s10875-014-0099-z","volume":"34","author":"Z Hel","year":"2014","unstructured":"Hel, Z. et al. Altered serum cytokine signature in common variable immunodeficiency. J. Clin. Immunol. 34, 971\u20138 (2014).","journal-title":"J. Clin. Immunol."},{"key":"BFsrep39710_CR49","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s12026-014-8620-2","volume":"61","author":"F Li","year":"2015","unstructured":"Li, F. et al. Insufficient secretion of IL-10 by Tregs compromised its control on over-activated CD4+ T effector cells in newly diagnosed adult immune thrombocytopenia patients. Immunol. Res. 61, 269\u2013280 (2015).","journal-title":"Immunol. Res."},{"issue":"5","key":"BFsrep39710_CR50","first-page":"1349-1356.e3","volume":"129","author":"Sayed Mahdi Marashi","year":"2012","unstructured":"Marashi, S. M. et al. Influence of cytomegalovirus infection on immune cell phenotypes in patients with common variable immunodeficiency. J. Allergy Clin. Immunol. 129, 1349\u20131356.e3 (2012).","journal-title":"Journal of Allergy and Clinical Immunology"},{"issue":"6","key":"BFsrep39710_CR51","first-page":"1385-1393.e4","volume":"127","author":"Sayed Mahdi Marashi","year":"2011","unstructured":"Marashi, S. M. et al. Inflammation in common variable immunodeficiency is associated with a distinct CD8(+) response to cytomegalovirus. J. Allergy Clin. Immunol. 127, 1385\u201393.e4 (2011).","journal-title":"Journal of Allergy and Clinical Immunology"},{"key":"BFsrep39710_CR52","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.clim.2015.05.020","volume":"160","author":"PA van Schouwenburg","year":"2015","unstructured":"van Schouwenburg, P. A. et al. Application of Whole Genome and Rna Sequencing to Investigate the Genomic Landscape of Common Variable Immunodeficiency. Clin. Immunol. 160, 301\u2013314 (2015).","journal-title":"Clin. Immunol."}],"updated-by":[{"DOI":"10.1038\/srep42569","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T00:00:00Z","timestamp":1488153600000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep39710.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39710","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39710.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T20:04:33Z","timestamp":1671825873000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep39710"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,5]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,5,2]]}},"alternative-id":["BFsrep39710"],"URL":"https:\/\/doi.org\/10.1038\/srep39710","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,5]]},"assertion":[{"value":"8 July 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 January 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2017","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has been fixed in the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"39710"}}