{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T20:18:31Z","timestamp":1789244311787,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad de Guadalajara","award":["PRO-SNI 2018"],"award-info":[{"award-number":["PRO-SNI 2018"]}]},{"name":"Universidad de Guadalajara","award":["PRO-SNI 2019"],"award-info":[{"award-number":["PRO-SNI 2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: The B-cell activating factor (BAFF) controls the maturation and survival of B cells. An imbalance in this cytokine has been associated with systemic autoimmunity in SLE and lupus nephritis (LN). However, few investigations have evaluated the tissular expression of BAFF in LN. This study aimed to associate BAFF system expression at the tissular level with the proliferative LN classes. Methods: The analysis included eighteen kidney tissues, with sixteen LN (class III = 5, class IV = 6, class III\/IV+V = 4, and class V = 1), and two controls. The tissular expression was evaluated with an immunochemistry assay. A Cytation5 imaging reader and ImageJ software were used to analyze the quantitative expression. A p-value &lt; 0.05 was considered significant. Results: The expressions of BAFF, A proliferation-inducing ligand (APRIL), and their receptors were observed in glomerular, tubular, and interstitial zones, with BAFF being the most strongly expressed in the overall analysis. BAFF-Receptor (BR3), transmembrane activator and CALM interactor (TACI), and B-Cell maturation antigen (BCMA) displayed higher expressions in LN class IV in all zones analyzed (p &lt; 0.05). Additionally, a positive correlation was found between APRIL, TACI, and BCMA at the glomerular level; BCMA and APRIL in the interstitial zone; and BR3, TACI, and BCMA in the tubule (p &lt; 0.05). Conclusions: The expression of BAFF and BAFF receptors is mainly associated with LN class IV, emphasizing the participation of these receptors as an essential pathogenic factor in kidney involvement in SLE patients.<\/jats:p>","DOI":"10.3390\/jcm12010071","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T02:31:11Z","timestamp":1671676271000},"page":"71","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Renal Tissue Expression of BAFF and BAFF Receptors Is Associated with Proliferative Lupus Nephritis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1658-8630","authenticated-orcid":false,"given":"Miguel","family":"Mar\u00edn-Rosales","sequence":"first","affiliation":[{"name":"Departamento de Reumatolog\u00eda, Hospital General de Occidente, Secretar\u00eda de Salud Jalisco, Guadalajara 45170, Mexico"},{"name":"Grupo de Inmunolog\u00eda Molecular, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-4186","authenticated-orcid":false,"given":"Claudia Azucena","family":"Palafox-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Grupo de Inmunolog\u00eda Molecular, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"},{"name":"Instituto de Investigaci\u00f3n en Ciencias Biom\u00e9dicas (IICB), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n Antonio","family":"Franco-Topete","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda y Patolog\u00eda, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Josu\u00e9","family":"Carrillo-Ballesteros","sequence":"additional","affiliation":[{"name":"Departamento de Farmacobiolog\u00eda, Centro Universitario de Ciencias Exactas e Ingenier\u00edas, Universidad de Guadalajara, Guadalajara 44430, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Cruz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Ciencias Biom\u00e9dicas (IICB), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Celeste","family":"Salazar-Camarena","sequence":"additional","affiliation":[{"name":"Grupo de Inmunolog\u00eda Molecular, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Francisco","family":"Mu\u00f1oz-Valle","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Ciencias Biom\u00e9dicas (IICB), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Ramos-Solano","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda y Patolog\u00eda, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1177\/0961203309358187","article-title":"Lupus Nephritis: Pathologic Features, Epidemiology and a Guide to Therapeutic Decisions","volume":"19","author":"Ortega","year":"2010","journal-title":"Lupus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1177\/0961203319889667","article-title":"Differences in Clinical Manifestations and Increased Severity of Systemic Lupus Erythematosus between Two Groups of Hispanics: European Caucasians versus Latin American Mestizos (Data from the RELESSER Registry)","volume":"29","author":"Alonso","year":"2020","journal-title":"Lupus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.clim.2016.08.001","article-title":"Lupus Nephritis Biomarkers","volume":"185","author":"Soliman","year":"2017","journal-title":"Clin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/acr.21664","article-title":"American College of Rheumatology Guidelines for Screening, Case Definition, Treatment and Management of Lupus Nephritis","volume":"64","author":"Hahn","year":"2012","journal-title":"Arthritis Care Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/j.1523-1755.2004.00443.x","article-title":"The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited","volume":"65","author":"Weening","year":"2004","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/rmdopen-2020-001263","article-title":"Management of Lupus Nephritis: A Systematic Literature Review Informing the 2019 Update of the Joint EULAR and European Renal Association-European Dialysis and Transplant Association (EULAR\/ERA-EDTA) Recommendations","volume":"6","author":"Kostopoulou","year":"2020","journal-title":"RMD Open"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1084\/jem.189.11.1747","article-title":"BAFF, a Novel Ligand of the Tumor Necrosis Factor Family, Stimulates B Cell Growth","volume":"189","author":"Schneider","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1084\/jem.188.6.1185","article-title":"APRIL, a New Ligand of the Tumor Necrosis Factor Family, Stimulates Tumor Cell Growth","volume":"188","author":"Hahne","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"807","DOI":"10.4049\/jimmunol.173.2.807","article-title":"B Cell-Activating Factor Belonging to the TNF Family (BAFF)-R Is the Principal BAFF Receptor Facilitating BAFF Costimulation of Circulating T and B Cells","volume":"173","author":"Ng","year":"2004","journal-title":"J. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1182\/blood-2007-09-110858","article-title":"APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells","volume":"111","author":"Belnoue","year":"2008","journal-title":"Blood"},{"key":"ref_11","first-page":"1","article-title":"Effect of TACI Signaling on Humoral Immunity and Autoimmune Diseases","volume":"2015","author":"Zhang","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1084\/jem.190.11.1697","article-title":"Mice Transgenic for Baff Develop Lymphocytic Disorders along with Autoimmune Manifestations","volume":"190","author":"Mackay","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1177\/0961203313496302","article-title":"Association of serum B cell activating factor from the tumour necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) with central nervous system and renal disease in systemic lupus erythematosus","volume":"22","author":"Vincent","year":"2013","journal-title":"Lupus"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e1047","DOI":"10.1002\/cti2.1047","article-title":"Analysis of serum B cell-activating factor from the tumor necrosis factor family (BAFF) and its soluble receptors in systemic lupus erythematosus","volume":"8","author":"Vincent","year":"2019","journal-title":"Clin. Transl. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1038\/35010115","article-title":"TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease","volume":"404","author":"Gross","year":"2000","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.kint.2018.03.012","article-title":"TACI deletion protects against progressive murine lupus nephritis induced by BAFF overexpression","volume":"94","author":"Arkatkar","year":"2018","journal-title":"Kidney Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e1950","DOI":"10.1002\/mgg3.1950","article-title":"Analysis of TNFSF13B polymorphisms and BAFF expression in rheumatoid arthritis and primary Sj\u00f6gren\u2019s syndrome patients","volume":"10","author":"Cruz","year":"2022","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1172\/JCI0214121","article-title":"Association of BAFF\/BLyS overexpression and altered B cell differentiation with Sj\u00f6gren\u2019s syndrome","volume":"109","author":"Groom","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1177\/0961203306071871","article-title":"B-lymphocyte activating factor in systemic lupus erythematosus and rheumatoid arthritis in relation to autoantibody levels, disease measures and time","volume":"15","author":"Nikolaisen","year":"2006","journal-title":"Lupus"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1136\/ard.2008.090928","article-title":"Serum levels of tumour necrosis factor family members a proliferation-inducing ligand (APRIL) and B lymphocyte stimulator (BLyS) are inversely correlated in systemic lupus erythematosus","volume":"68","author":"Morel","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.cyto.2018.11.008","article-title":"BAFF-R and TACI expression on CD3+ T cells: Interplay among BAFF, APRIL and T helper cytokines profile in systemic lupus erythematosus","volume":"114","author":"Cruz","year":"2019","journal-title":"Cytokine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s10238-019-00549-8","article-title":"High BAFF expression associated with active disease in systemic lupus erythematosus and relationship with rs9514828C>T polymorphism in TNFSF13B gene","volume":"19","author":"Cruz","year":"2019","journal-title":"Clin. Exp. Med."},{"key":"ref_23","first-page":"582","article-title":"Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus","volume":"25","author":"Cruz","year":"2015","journal-title":"Lupus"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1002\/art.37995","article-title":"Baseline Predictors of Systemic Lupus Erythematosus Flares: Data From the Combined Placebo Groups in the Phase III Belimumab Trials","volume":"65","author":"Petri","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6236","DOI":"10.1038\/s41598-020-63390-0","article-title":"Analysis of the receptor BCMA as a biomarker in systemic lupus erythematosus patients","volume":"10","author":"Cruz","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1159\/000517852","article-title":"Prognostic and Diagnostic Values of Novel Serum and Urine Biomarkers in Lupus Nephritis: A Systematic Review","volume":"52","author":"Radin","year":"2021","journal-title":"Am. J. Nephrol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1177\/0961203317739132","article-title":"Profile of BAFF and its receptors\u2019 expression in lupus nephritis is associated with pathological classes","volume":"27","author":"Suso","year":"2018","journal-title":"Lupus"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1002\/art.34473","article-title":"Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus","volume":"64","author":"Petri","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_29","first-page":"2053","article-title":"B-cell activating factor receptor expression is associated with germinal center B-cell maintenance","volume":"17","author":"Cruz","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chatterjee, S., Malhotra, R., Varghese, F., Bukhari, A.B., Patil, A., Budrukkar, A., Parmar, V., Gupta, S., and De, A. (2013). Quantitative Immunohistochemical Analysis Reveals Association between Sodium Iodide Symporter and Estrogen Receptor Expression in Breast Cancer. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054055"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/rheumatology\/ket322","article-title":"Identification of clinical predictors of flare in systemic lupus erythematosus patients: A 24-month prospective cohort study","volume":"53","author":"Duarte","year":"2014","journal-title":"Rheumatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1002\/art.39594","article-title":"Risk of End-Stage Renal Disease in Patients With Lupus Nephritis, 1971-2015: A Systematic Review and Bayesian Meta-Analysis","volume":"68","author":"Tektonidou","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.2215\/CJN.01570219","article-title":"Sensitivity and Specificity of Pathologic Findings to Diagnose Lupus Nephritis","volume":"14","author":"Kudose","year":"2019","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"734","DOI":"10.2215\/CJN.10601016","article-title":"Clinical and Histopathologic Characteristics Associated with Renal Outcomes in Lupus Nephritis","volume":"12","author":"Rijnink","year":"2017","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1111\/cei.12894","article-title":"Urinary B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL): Potential biomarkers of active lupus nephritis","volume":"187","author":"Phatak","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100027","DOI":"10.1016\/j.jtauto.2019.100027","article-title":"Expression of BAFF, APRIL, and cognate receptor genes in lupus nephritis and potential use as urinary biomarkers","volume":"3","author":"Castro","year":"2020","journal-title":"J. Transl. Autoimmun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1600281","DOI":"10.4049\/jimmunol.1600281","article-title":"BAFF Induces Tertiary Lymphoid Structures and Positions T Cells within the Glomeruli during Lupus Nephritis","volume":"198","author":"Kang","year":"2017","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/cei.12380","article-title":"Pathogenetic role of glomerular CXCL13 expression in lupus nephritis","volume":"178","author":"Worthmann","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.3389\/fimmu.2020.01204","article-title":"Ischemia Reperfusion Injury Triggers CXCL13 Release and B-Cell Recruitment After Allogenic Kidney Transplantation","volume":"11","author":"Kreimann","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Schiffer, L., Wiehler, F., Br\u00e4sen, J.H., Gwinner, W., Greite, R., Kreimann, K., Thorenz, A., Derlin, K., Teng, B., and Rong, S. (2019). Chemokine CXCL13 as a New Systemic Biomarker for B-Cell Involvement in Acute T Cell-Mediated Kidney Allograft Rejection. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102552"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1177\/0961203317717083","article-title":"Renal tubular epithelial cell-derived BAFF expression mediates kidney damage and correlates with activity of proliferative lupus nephritis in mouse and men","volume":"27","author":"Schwarting","year":"2018","journal-title":"Lupus"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5948","DOI":"10.4049\/jimmunol.0901186","article-title":"Adipocytes as Immune Cells: Differential Expression of TWEAK, BAFF, and APRIL and Their Receptors (Fn14, BAFF-R, TACI, and BCMA) at Different Stages of Normal and Pathological Adipose Tissue Development","volume":"183","author":"Alexaki","year":"2009","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1210\/en.2011-1504","article-title":"B-Cell Maturation Antigen (BCMA) Activation Exerts Specific Proinflammatory Effects in Normal Human Keratinocytes and Is Preferentially Expressed in Inflammatory Skin Pathologies","volume":"153","author":"Alexaki","year":"2012","journal-title":"Endocrinology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1189\/jlb.1008659","article-title":"Functional implication of BAFF synthesis and release in gangliosides-stimulated microglia","volume":"86","author":"Kim","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s40265-018-0872-z","article-title":"Belimumab: A Review in Systemic Lupus Erythematosus","volume":"78","author":"Blair","year":"2018","journal-title":"Drugs"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1056\/NEJMoa2001180","article-title":"Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis","volume":"383","author":"Furie","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_47","first-page":"e20440","article-title":"Belimumab in Lupus Nephritis: A Systematic Review and Meta-Analysis","volume":"13","author":"Shrestha","year":"2021","journal-title":"Cureus"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/art.41466","article-title":"Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis","volume":"73","author":"Malkiel","year":"2021","journal-title":"Arthritis Rheumatol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/1\/71\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:47:28Z","timestamp":1760147248000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/1\/71"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,22]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["jcm12010071"],"URL":"https:\/\/doi.org\/10.3390\/jcm12010071","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,22]]}}}