{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:53:44Z","timestamp":1791831224239,"version":"4.3.4"},"reference-count":67,"publisher":"Portland Press Ltd.","issue":"9","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,5,1]]},"abstract":"<jats:p>IgAN (IgA nephropathy) is the most common form of primary glomerulonephritis worldwide and has a strong genetic component. In this setting, DNA methylation could also be an important factor influencing this disease. We performed a genome-wide screening for DNA methylation in CD4+ T-cells from IgAN patients and found three regions aberrantly methylated influencing genes involved in the response and proliferation of CD4+ T-cells. Two hypomethylated regions codified genes involved in TCR (T-cell receptor) signalling, TRIM27 (tripartite motif-containing 27) and DUSP3 (dual-specificity phosphatase 3), and an hypermethylated region included the VTRNA2-1 (vault RNA 2-1) non-coding RNA, also known as miR-886 precursor. We showed that the aberrant methylation influences the expression of these genes in IgAN patients. Moreover, we demonstrated that the hypermethylation of the miR-886 precursor led to a decreased CD4+ T-cell proliferation following TCR stimulation and to the overexpression of TGF\u03b2 (transforming growth factor \u03b2). Finally, we found a Th1\/Th2 imbalance in IgAN patients. The IL (interleukin)-2\/IL-5 ratio was notably higher in IgAN patients and clearly indicated a Th1 shift. In conclusion, we identified for the first time some specific DNA regions abnormally methylated in IgAN patients that led to the reduced TCR signal strength of the CD4+ T-cells and to their anomalous response and activation that could explain the T-helper cell imbalance. The present study reveals new molecular mechanisms underlying the abnormal CD4+ T-cell response in IgAN patients.<\/jats:p>","DOI":"10.1042\/cs20150711","type":"journal-article","created":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T21:13:50Z","timestamp":1454620430000},"page":"733-746","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Aberrantly methylated DNA regions lead to low activation of CD4+ T-cells in IgA nephropathy"],"prefix":"10.1042","volume":"130","author":[{"given":"Fabio","family":"Sallustio","sequence":"first","affiliation":[{"name":"University of Bari, DETO, Bari, Italy"},{"name":"Universit\u00e0 del Salento, DiSTeBA, Lecce, Italy"},{"name":"C.A.R.S.O. Consortium, Valenzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Serino","sequence":"additional","affiliation":[{"name":"University of Bari, DETO, Bari, Italy"},{"name":"IRCCS \u201cde Bellis\u201d, Laboratory of Experimental Immunopathology, 70013 Castellana Grotte, BA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon\u00a0N.","family":"Cox","sequence":"additional","affiliation":[{"name":"University of Bari, DETO, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra\u00a0Dalla","family":"Gassa","sequence":"additional","affiliation":[{"name":"University of Verona, Department of Medicine, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Curci","sequence":"additional","affiliation":[{"name":"C.A.R.S.O. Consortium, Valenzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"De Palma","sequence":"additional","affiliation":[{"name":"C.A.R.S.O. Consortium, Valenzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Banelli","sequence":"additional","affiliation":[{"name":"IRCCS AOU San Martino-IST, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Zaza","sequence":"additional","affiliation":[{"name":"IRCCS \u201cde Bellis\u201d, Laboratory of Experimental Immunopathology, 70013 Castellana Grotte, BA, Italy"},{"name":"University of Verona, Department of Medicine, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Romani","sequence":"additional","affiliation":[{"name":"IRCCS AOU San Martino-IST, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco\u00a0P.","family":"Schena","sequence":"additional","affiliation":[{"name":"University of Bari, DETO, Bari, Italy"},{"name":"C.A.R.S.O. Consortium, Valenzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2016,3,18]]},"reference":[{"key":"2021113010472810400_B1","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/nature05913","article-title":"Perceptions of epigenetics","volume":"447","author":"Bird","year":"2007","journal-title":"Nature"},{"key":"2021113010472810400_B2","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1001\/archneurol.2010.275","article-title":"Emerging role of epigenetics in stroke. Part 1: DNA methylation and chromatin modifications","volume":"67","author":"Qureshi","year":"2010","journal-title":"Arch. Neurol."},{"key":"2021113010472810400_B3","first-page":"81","article-title":"Epigenetics of complex diseases: from general theory to laboratory experiments","volume":"310","author":"Schumacher","year":"2006","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"2021113010472810400_B4","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/nm.2135","article-title":"Methylation determines fibroblast activation and fibrogenesis in the kidney","volume":"16","author":"Bechtel","year":"2010","journal-title":"Nat. Med."},{"key":"2021113010472810400_B5","doi-asserted-by":"publisher","first-page":"R108","DOI":"10.1186\/gb-2013-14-10-r108","article-title":"Cytosine methylation changes in enhancer regions of core pro-fibrotic genes characterize kidney fibrosis development","volume":"14","author":"Ko","year":"2013","journal-title":"Genome Biol."},{"key":"2021113010472810400_B6","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1086\/510135","article-title":"Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci","volume":"79","author":"Bisceglia","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"2021113010472810400_B7","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/ng.787","article-title":"Genome-wide association study identifies susceptibility loci for IgA nephropathy","volume":"43","author":"Gharavi","year":"2011","journal-title":"Nat. Genet."},{"key":"2021113010472810400_B8","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1038\/ejhg.2014.208","article-title":"Genome-wide scan identifies a copy number variable region at 3p21.1 that influences the TLR9 expression levels in IgA nephropathy patients","volume":"23","author":"Sallustio","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"2021113010472810400_B9","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1038\/ng.1047","article-title":"A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy","volume":"44","author":"Yu","year":"2012","journal-title":"Nat. Genet."},{"key":"2021113010472810400_B10","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/81677","article-title":"IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22\u20136q23","volume":"26","author":"Gharavi","year":"2000","journal-title":"Nat. Genet."},{"key":"2021113010472810400_B11","first-page":"1668","article-title":"Aberrantly glycosylated IgA1\u00a0in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity","volume":"119","author":"Suzuki","year":"2009","journal-title":"J. Clin. Invest."},{"key":"2021113010472810400_B12","doi-asserted-by":"publisher","first-page":"2325","DOI":"10.1172\/JCI74475","article-title":"The genetics and immunobiology of IgA nephropathy","volume":"124","author":"Kiryluk","year":"2014","journal-title":"J. Clin. Invest."},{"key":"2021113010472810400_B13","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1681\/ASN.2011050464","article-title":"The pathophysiology of IgA nephropathy","volume":"22","author":"Suzuki","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"2021113010472810400_B14","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.trre.2013.07.004","article-title":"Recurrence of glomerulonephritis after renal transplantation","volume":"27","author":"Sprangers","year":"2013","journal-title":"Transplant. Rev. (Orlando)"},{"key":"2021113010472810400_B15","first-page":"419","article-title":"Detection of polymeric IgA in glomeruli from patients with IgA nephropathy","volume":"49","author":"Tomino","year":"1982","journal-title":"Clin. Exp. Immunol."},{"key":"2021113010472810400_B16","doi-asserted-by":"publisher","first-page":"2540","DOI":"10.1093\/ndt\/gfm228","article-title":"T-cell homing receptor expression in IgA nephropathy","volume":"22","author":"Batra","year":"2007","journal-title":"Nephrol. Dial. Transplant."},{"key":"2021113010472810400_B17","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1002\/path.1711740104","article-title":"CD4-positive cells from patients with IgA nephropathy demonstrate increased mRNA of cytokines that induce the IgA switch and differentiation","volume":"174","author":"Lai","year":"1994","journal-title":"J. Pathol."},{"key":"2021113010472810400_B18","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1038\/ki.1994.343","article-title":"Increased mRNA encoding for transforming factor-\u03b2; in CD4+ cells from patients with IgA nephropathy","volume":"46","author":"Lai","journal-title":"Kidney Int."},{"key":"2021113010472810400_B19","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1038\/nmeth.3115","article-title":"Comprehensive analysis of DNA methylation data with RnBeads","volume":"11","author":"Assenov","year":"2014","journal-title":"Nat. Methods"},{"key":"2021113010472810400_B20","doi-asserted-by":"publisher","first-page":"48","DOI":"10.2144\/000112312","article-title":"Optimizing annealing temperature overcomes bias in bisulfite PCR methylation analysis","volume":"42","author":"Shen","year":"2007","journal-title":"BioTechniques"},{"key":"2021113010472810400_B21","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1038\/labinvest.2011.169","article-title":"A pyrosequencing assay for the quantitative methylation analysis of the PCDHB gene cluster, the major factor in neuroblastoma methylator phenotype","volume":"92","author":"Banelli","year":"2012","journal-title":"Lab. Invest."},{"key":"2021113010472810400_B22","first-page":"3410","article-title":"Epigenetic patterns in the progression of esophageal adenocarcinoma","volume":"61","author":"Eads","year":"2001","journal-title":"Cancer Res."},{"key":"2021113010472810400_B23","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1261\/rna.2701111","article-title":"Precursor miR-886, a novel noncoding RNA repressed in cancer, associates with PKR and modulates its activity","volume":"17","author":"Lee","year":"2011","journal-title":"RNA."},{"key":"2021113010472810400_B24","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1093\/ndt\/16.2.269","article-title":"Th1\/Th2 predominance and proinflammatory cytokines determine the clinicopathological severity of IgA nephropathy","volume":"16","author":"Lim","year":"2001","journal-title":"Nephrol. Dial. Transplant."},{"key":"2021113010472810400_B25","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1093\/ndt\/gfp620","article-title":"Worldwide distribution of glomerular diseases: the role of renal biopsy registries","volume":"25","author":"Pesce","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"2021113010472810400_B26","first-page":"626","article-title":"Innate immunity and IgA nephropathy","volume":"23","author":"Coppo","year":"2010","journal-title":"J. Nephrol."},{"key":"2021113010472810400_B27","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/ki.1997.361","article-title":"Galactose-deficient IgA1\u00a0in sera of IgA nephropathy patients is present in complexes with IgG","volume":"52","author":"Tomana","year":"1997","journal-title":"Kidney Int."},{"key":"2021113010472810400_B28","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1172\/JCI5535","article-title":"Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies","volume":"104","author":"Tomana","year":"1999","journal-title":"J. Clin. Invest."},{"key":"2021113010472810400_B29","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/ki.2010.138","article-title":"Altered modulation of WNT\u2013\u03b2-catenin and PI3K\/Akt pathways in IgA nephropathy","volume":"78","author":"Cox","year":"2010","journal-title":"Kidney Int."},{"key":"2021113010472810400_B30","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1093\/ndt\/gfv017","article-title":"Altered monocyte expression and expansion of non-classical monocyte subset in IgA nephropathy patients","volume":"30","author":"Cox","year":"2015","journal-title":"Nephrol. Dial. Transplant."},{"key":"2021113010472810400_B31","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/j.jaci.2010.09.026","article-title":"Innate signals in mucosal immunoglobulin class switching","volume":"126","author":"Puga","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"2021113010472810400_B32","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1146\/annurev.immunol.22.012703.104533","article-title":"CD40\/CD154 interactions at the interface of tolerance and immunity","volume":"22","author":"Quezada","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"2021113010472810400_B33","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1146\/annurev.immunol.021908.132706","article-title":"T cell activation","volume":"27","author":"Smith-Garvin","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"2021113010472810400_B34","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/mi.2014.121","article-title":"Lactoferrin causes IgA and IgG2b isotype switching through betaglycan binding and activation of canonical TGF-\u03b2 signaling","volume":"8","author":"Jang","year":"2015","journal-title":"Mucosal Immunol."},{"key":"2021113010472810400_B35","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1189\/jlb.0313128","article-title":"Retinoic acid, acting as a highly specific IgA isotype switch factor, cooperates with TGF-\u03b21 to enhance the overall IgA response","volume":"94","author":"Seo","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"2021113010472810400_B36","doi-asserted-by":"publisher","first-page":"4766","DOI":"10.1074\/jbc.M006497200","article-title":"Inhibitory role for dual specificity phosphatase VHR in T cell antigen receptor and CD28-induced Erk and Jnk activation","volume":"276","author":"Alonso","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2021113010472810400_B37","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1038\/ncb1447","article-title":"Negative regulation of ERK activity by VRK3-mediated activation of VHR phosphatase","volume":"8","author":"Kang","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"2021113010472810400_B38","doi-asserted-by":"publisher","first-page":"13271","DOI":"10.1074\/jbc.274.19.13271","article-title":"Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase VHR: a novel role in down-regulating the ERK pathway","volume":"274","author":"Todd","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2021113010472810400_B39","doi-asserted-by":"publisher","first-page":"20072","DOI":"10.1073\/pnas.1111233109","article-title":"Tripartite motif containing protein 27 negatively regulates CD4 T cells by ubiquitinating and inhibiting the class II PI3K-C2\u03b2","volume":"108","author":"Cai","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010472810400_B40","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s00018-008-8364-z","article-title":"Vaults and the major vault protein: novel roles in signal pathway regulation and immunity","volume":"66","author":"Berger","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"2021113010472810400_B41","doi-asserted-by":"publisher","first-page":"3326","DOI":"10.1158\/0008-5472.CAN-12-3055","article-title":"DNA methylation-mediated repression of miR-886-83p predicts poor outcome of human small cell lung cancer","volume":"73","author":"Cao","year":"2013","journal-title":"Cancer Res."},{"key":"2021113010472810400_B42","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.biochi.2007.03.001","article-title":"The dsRNA protein kinase PKR: virus and cell control","volume":"89","author":"Garcia","year":"2007","journal-title":"Biochimie"},{"key":"2021113010472810400_B43","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/gene.2012.63","article-title":"The TGF-\u03b2\u2013Smad3 pathway inhibits CD28-dependent cell growth and proliferation of CD4 T cells","volume":"14","author":"Delisle","year":"2013","journal-title":"Genes Immun."},{"key":"2021113010472810400_B44","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/S1074-7613(00)00044-3","article-title":"TGF-\u03b2 receptor controls B cell responsiveness and induction of IgA in\u00a0vivo","volume":"13","author":"Cazac","year":"2000","journal-title":"Immunity"},{"key":"2021113010472810400_B45","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.4049\/jimmunol.145.11.3773","article-title":"Transforming growth factor \u03b21 increases IgA isotype switching at the clonal level","volume":"145","author":"Kim","year":"1990","journal-title":"J. Immunol."},{"key":"2021113010472810400_B46","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.4049\/jimmunol.163.4.1951","article-title":"Partial IgA-deficiency with increased Th2-type cytokines in TGF-\u03b21 knockout mice","volume":"163","author":"van Ginkel","year":"1999","journal-title":"J. Immunol."},{"key":"2021113010472810400_B47","doi-asserted-by":"crossref","first-page":"5217","DOI":"10.4049\/jimmunol.161.10.5217","article-title":"CD40 engagement triggers switching to IgA1 and IgA2\u00a0in human B cells through induction of endogenous TGF-\u03b2: evidence for TGF-\u03b2 but not IL-10-dependent direct S\u03bc\u2192S\u03b1 and sequential S\u03bc\u2192S\u03b3, S\u03b3\u2192S\u03b1 DNA recombination","volume":"161","author":"Zan","year":"1998","journal-title":"J. Immunol."},{"key":"2021113010472810400_B48","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/nri2131","article-title":"Molecular mechanisms of CD4+ T-cell anergy","volume":"7","author":"Fathman","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"2021113010472810400_B49","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/ni1047","article-title":"Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins","volume":"5","author":"Heissmeyer","year":"2004","journal-title":"Nat. Immunol."},{"key":"2021113010472810400_B50","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/ni763","article-title":"Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiation","volume":"3","author":"Fang","year":"2002","journal-title":"Nat. Immunol."},{"key":"2021113010472810400_B51","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.4049\/jimmunol.157.5.2048","article-title":"Defective transcription of the IL-2 gene is associated with impaired expression of c-Fos, FosB, and JunB in anergic T helper 1 cells","volume":"157","author":"Mondino","year":"1996","journal-title":"J. Immunol."},{"key":"2021113010472810400_B52","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1084\/jem.20051304","article-title":"Independent roles for IL-2 and GATA-3\u00a0in stimulating naive CD4+ T cells to generate a Th2-inducing cytokine environment","volume":"202","author":"Yamane","year":"2005","journal-title":"J. Exp. Med."},{"key":"2021113010472810400_B53","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1111\/sji.12175","article-title":"On the mechanism determining the TH1\/TH2 phenotype of an immune response, and its pertinence to strategies for the prevention, and treatment, of certain infectious diseases","volume":"79","author":"Bretscher","year":"2014","journal-title":"Scand. J. Immunol."},{"key":"2021113010472810400_B54","doi-asserted-by":"publisher","first-page":"25","DOI":"10.2217\/imt.09.80","article-title":"Immunization of newborn and adult mice with low numbers of BCG leads to Th1 responses, Th1 imprints and enhanced protection upon BCG challenge","volume":"2","author":"Kiros","year":"2010","journal-title":"Immunotherapy"},{"key":"2021113010472810400_B55","doi-asserted-by":"publisher","first-page":"4020","DOI":"10.1002\/(SICI)1521-4141(199812)28:12&lt;4020::AID-IMMU4020&gt;3.0.CO;2-3","article-title":"Parasite dose determines the Th1\/Th2 nature of the response to Leishmania major independently of infection route and strain of host or parasite","volume":"28","author":"Menon","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"2021113010472810400_B56","doi-asserted-by":"crossref","first-page":"5743","DOI":"10.1128\/IAI.66.12.5743-5750.1998","article-title":"Mycobacterial dose defines the Th1\/Th2 nature of the immune response independently of whether immunization is administered by the intravenous, subcutaneous, or intradermal route","volume":"66","author":"Power","year":"1998","journal-title":"Infect. Immun."},{"key":"2021113010472810400_B57","doi-asserted-by":"publisher","first-page":"2955","DOI":"10.4049\/jimmunol.164.6.2955","article-title":"CD28, Ox-40, LFA-1, and CD4 modulation of Th1\/Th2 differentiation is directly dependent on the dose of antigen","volume":"164","author":"Rogers","year":"2000","journal-title":"J. Immunol."},{"key":"2021113010472810400_B58","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.4049\/jimmunol.170.3.1218","article-title":"Differential antigen sensitivity and costimulatory requirements in human Th1 and Th2 antigen-specific CD4+ cells with similar TCR avidity","volume":"170","author":"Holzer","year":"2003","journal-title":"J. Immunol."},{"key":"2021113010472810400_B59","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.4049\/jimmunol.163.3.1205","article-title":"Peptide dose, affinity, and time of differentiation can contribute to the Th1\/Th2 cytokine balance","volume":"163","author":"Rogers","year":"1999","journal-title":"J. Immunol."},{"key":"2021113010472810400_B60","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.4049\/jimmunol.131.3.1103","article-title":"In\u00a0vitro analysis of the cellular interactions between unprimed lymphocytes responsible for determining the class of response an antigen induces: specific T cells switch a cell-mediated response to a humoral response","volume":"131","author":"Bretscher","year":"1983","journal-title":"J. Immunol."},{"key":"2021113010472810400_B61","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1111\/j.1365-2567.2005.02128.x","article-title":"Increasing the foreignness of an antigen, by coupling a second and foreign antigen to it, increases the T helper type\u00a02 component of the immune response to the first antigen","volume":"115","author":"Ismail","year":"2005","journal-title":"Immunology"},{"key":"2021113010472810400_B62","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1002\/1521-4141(200106)31:6&lt;1765::AID-IMMU1765&gt;3.0.CO;2-T","article-title":"More antigen-dependent CD4+ T cell\/CD4+ T cell interactions are required for the primary generation of Th2 than of Th1 cells","volume":"31","author":"Ismail","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"2021113010472810400_B63","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/0090-1229(89)90032-9","article-title":"Glomerular and serum immunoglobulin G subclasses in IgA nephropathy","volume":"51","author":"Aucouturier","year":"1989","journal-title":"Clin. Immunol. Immunopathol."},{"key":"2021113010472810400_B64","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1146\/annurev.iy.08.040190.001511","article-title":"Lymphokine control of in\u00a0vivo immunoglobulin isotype selection","volume":"8","author":"Finkelman","year":"1990","journal-title":"Annu. Rev. Immunol."},{"key":"2021113010472810400_B65","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1046\/j.1523-1755.1999.00369.x","article-title":"Th1 and Th2 T helper cell subsets affect patterns of injury and outcomes in glomerulonephritis","volume":"55","author":"Holdsworth","year":"1999","journal-title":"Kidney Int."},{"key":"2021113010472810400_B66","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1038\/ki.1989.67","article-title":"Increased production of interleukin-2 and IL-2 receptor in primary IgA nephropathy","volume":"35","author":"Schena","year":"1989","journal-title":"Kidney Int."},{"key":"2021113010472810400_B67","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/sj.ki.5002300","article-title":"Th1 polarization in murine IgA nephropathy directed by bone marrow-derived cells","volume":"72","author":"Suzuki","year":"2007","journal-title":"Kidney Int."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/130\/9\/733\/447580\/cs1300733.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/130\/9\/733\/447580\/cs1300733.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T01:26:17Z","timestamp":1718328377000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/130\/9\/733\/71526\/Aberrantly-methylated-DNA-regions-lead-to-low"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,18]]},"references-count":67,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,5,1]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20150711","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,18]]}}}