{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:44:56Z","timestamp":1790675096609,"version":"4.1.0"},"reference-count":49,"publisher":"BMJ","issue":"7","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2018,1,5]]},"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Humoral immunity and B cells are thought to play an important role in the pathophysiology of the systemic sclerosis (SSc). The production of free light chains (FLC) of immunoglobulins is abnormally high in several pathological autoimmune conditions and reflects B cell activation. Furthermore, FLCs demonstrated different biological activities including their capability to modulate the immune system, proteolytic activity and complement cascade activation. The aims of this study are to determine the FLC levels in patients with SSc compared with healthy controls (HC) and to study their possible association with organ involvement and disease characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty-five patients with SSc and 20 HC were studied. Clinical and immunological inflammatory characteristics were assessed for all the patients with SSc. \u03ba-FLC and \u03bb-FLC, interleukin 6 (IL-6) and B cell activating factor levels were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The mean serum \u03ba-FLC levels and FLC ratio were significantly higher in patients with SSc compared with HC, while the serum \u03bb-FLC levels were comparable.<\/jats:p>\n                    <jats:p>The levels of FLC were comparable in patients with diffuse skin disease and limited skin involvement, while \u03ba-FLC levels were increased in patients with restrictive lung (forced vital capacity (FVC) &lt;80%) disease (26.4\u00b17.4\u2009mg\/L) when compared with patients with FVC \u226580% (19.6\u00b17.3\u2009mg\/L, P=0.009). In patients with SSc, the levels of serum \u03ba-FLC level directly correlated with the IL-6 levels (R=0.3, P=0.001) and disease activity (R=0.4, P=0.003).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>FLC levels are elevated in SSc and high levels are associated with lung involvement and with a higher degree of inflammation, supporting a possible role of B cell activation in the pathophysiology of the disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jclinpath-2017-204656","type":"journal-article","created":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T11:25:56Z","timestamp":1531913156000},"page":"620-625","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Free light chains of immunoglobulins in patients with systemic sclerosis: correlations with lung involvement and inflammatory milieu"],"prefix":"10.1136","volume":"71","author":[{"given":"Silvia","family":"Bosello","sequence":"first","affiliation":[{"name":"Institute of Rheumatology and Affine Sciences, Department of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8328-2570","authenticated-orcid":false,"given":"Umberto","family":"Basile","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Fondazione Policlinico Universitario Agostino Gemelli, Catholic University of the Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"De Lorenzis","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Affine Sciences, Department of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Gulli","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Fondazione Policlinico Universitario Agostino Gemelli, Catholic University of the Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Canestrari","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Affine Sciences, Department of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Napodano","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Fondazione Policlinico Universitario Agostino Gemelli, Catholic University of the Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Parisi","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Affine Sciences, Department of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krizia","family":"Pocino","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Fondazione Policlinico Universitario Agostino Gemelli, Catholic University of the Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Di Mario","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Affine Sciences, Department of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Tolusso","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Affine Sciences, Department of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Ferraccioli","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Affine Sciences, Department of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Gremese","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Affine Sciences, Department of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2018,1,31]]},"reference":[{"key":"2025120523561270000_71.7.620.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2011.04.013"},{"key":"2025120523561270000_71.7.620.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2007.10.010"},{"key":"2025120523561270000_71.7.620.3","doi-asserted-by":"publisher","DOI":"10.1016\/S1568-9972(03)00005-3"},{"key":"2025120523561270000_71.7.620.4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2147\/ITT.S82037","article-title":"Current perspectives on the immunopathogenesis of systemic sclerosis","volume":"5","author":"Fuschiotti","year":"2016","journal-title":"Immunotargets Ther"},{"key":"2025120523561270000_71.7.620.5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1346-8138.2009.00763.x","article-title":"B lymphocytes: shedding new light on the pathogenesis of systemic sclerosis","volume":"37","author":"Hasegawa","year":"2010","journal-title":"J Dermatol"},{"key":"2025120523561270000_71.7.620.6","first-page":"59","article-title":"Polyclonal B lymphocyte activation in progressive systemic sclerosis","volume":"29","author":"Famularo","year":"1989","journal-title":"J Clin Lab Immunol"},{"key":"2025120523561270000_71.7.620.7","doi-asserted-by":"publisher","DOI":"10.1002\/art.20274"},{"key":"2025120523561270000_71.7.620.8","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6635"},{"key":"2025120523561270000_71.7.620.9","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2011.65"},{"key":"2025120523561270000_71.7.620.10","doi-asserted-by":"crossref","first-page":"5121","DOI":"10.4049\/jimmunol.153.11.5121","article-title":"Proteolytic activity of an antibody light chain","volume":"153","author":"Sun","year":"1994","journal-title":"J Immunol"},{"key":"2025120523561270000_71.7.620.11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.175.4.939"},{"key":"2025120523561270000_71.7.620.12","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/S0021-9258(17)42411-2","article-title":"Antigen recognition by an antibody light chain","volume":"269","author":"Sun","year":"1994","journal-title":"J Biol Chem"},{"key":"2025120523561270000_71.7.620.13","doi-asserted-by":"publisher","DOI":"10.1038\/nm722"},{"key":"2025120523561270000_71.7.620.14","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073176"},{"key":"2025120523561270000_71.7.620.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2010.09.002"},{"key":"2025120523561270000_71.7.620.16","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.052159"},{"key":"2025120523561270000_71.7.620.17","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/j.0954-6820.1981.tb11632.x","article-title":"Free light chains of immunoglobulins in serum from patients with rheumatoid arthritis, sarcoidosis, chronic infections and pulmonary cancer","volume":"209","author":"S\u00f8lling","year":"1981","journal-title":"Acta Med Scand"},{"key":"2025120523561270000_71.7.620.18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0059868","article-title":"Serum levels of beta2-microglobulin and free light chains of immunoglobulins are associated with systemic disease activity in primary Sj\u00f6gren\u2019s syndrome. Data at enrollment in the prospective ASSESS cohort","volume":"8","author":"Gottenberg","year":"2013","journal-title":"PLoS One"},{"key":"2025120523561270000_71.7.620.19","doi-asserted-by":"publisher","DOI":"10.1177\/0961203314530793"},{"key":"2025120523561270000_71.7.620.20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901129"},{"key":"2025120523561270000_71.7.620.21","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.kjms.2013.01.013","article-title":"Judging disease activity in rheumatoid arthritis by serum free kappa and lambda light chain levels","volume":"29","author":"Ye","year":"2013","journal-title":"Kaohsiung J Med Sci"},{"key":"2025120523561270000_71.7.620.22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0138753","article-title":"Elevated concentrations of serum immunoglobulin free light chains in systemic lupus erythematosus patients in relation to disease activity, inflammatory status, b cell activity and epstein-barr virus antibodies","volume":"10","author":"Draborg","year":"2015","journal-title":"PLoS One"},{"key":"2025120523561270000_71.7.620.23","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.autrev.2014.07.003","article-title":"Serum free light chains of immunoglobulins as biomarkers for systemic sclerosis characteristics, activity and severity","volume":"13","author":"Lanteri","year":"2014","journal-title":"Autoimmun Rev"},{"key":"2025120523561270000_71.7.620.24","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230510"},{"key":"2025120523561270000_71.7.620.25","first-page":"202","article-title":"Scleroderma (systemic sclerosis): classification, subsets and pathogenesis","volume":"15","author":"LeRoy","year":"1988","journal-title":"J Rheumatol"},{"key":"2025120523561270000_71.7.620.26","first-page":"S39","article-title":"Assessment of disease activity","volume":"21","author":"Valentini","year":"2003","journal-title":"Clin Exp Rheumatol"},{"key":"2025120523561270000_71.7.620.27","first-page":"S42","article-title":"Assessment of disease severity and prognosis","volume":"21","author":"Medsger","year":"2003","journal-title":"Clin Exp Rheumatol"},{"key":"2025120523561270000_71.7.620.28","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.3.7663792"},{"key":"2025120523561270000_71.7.620.29","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.6.8520796"},{"key":"2025120523561270000_71.7.620.30","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken313"},{"key":"2025120523561270000_71.7.620.31","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.2.ats3-00"},{"key":"2025120523561270000_71.7.620.32","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20446"},{"key":"2025120523561270000_71.7.620.33","doi-asserted-by":"publisher","DOI":"10.1186\/ar2773"},{"key":"2025120523561270000_71.7.620.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.12.065"},{"key":"2025120523561270000_71.7.620.35","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1177\/0004563216652175","article-title":"Multiple sclerosis: assay of free immunoglobulin light chains","volume":"54","author":"Ramsden","year":"2017","journal-title":"Ann Clin Biochem"},{"key":"2025120523561270000_71.7.620.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2014.08.003"},{"key":"2025120523561270000_71.7.620.37","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040818"},{"key":"2025120523561270000_71.7.620.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2008.01.004"},{"key":"2025120523561270000_71.7.620.39","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.abb.2004.08.022","article-title":"Purification and characterization of a stimulator of plasmin generation from the antiangiogenic agent Neovastat: identification as immunoglobulin kappa light chain","volume":"431","author":"Boivin","year":"2004","journal-title":"Arch Biochem Biophys"},{"key":"2025120523561270000_71.7.620.40","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3410\/M5-4","article-title":"Polyclonal free light chains: a biomarker of inflammatory disease or treatment target?","volume":"5","author":"Brebner","year":"2013","journal-title":"F1000 Med Rep"},{"key":"2025120523561270000_71.7.620.41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/blood.V74.1.1.1","article-title":"The biology of interleukin-6","volume":"74","author":"Kishimoto","year":"1989","journal-title":"Blood"},{"key":"2025120523561270000_71.7.620.42","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/1523-1747.ep12483971","article-title":"Stimulation of collagen and glycosaminoglycan production in cultured human adult dermal fibroblasts by recombinant human interleukin 6","volume":"97","author":"Duncan","year":"1991","journal-title":"J Invest Dermatol"},{"key":"2025120523561270000_71.7.620.43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2004.02642.x"},{"key":"2025120523561270000_71.7.620.44","first-page":"308","article-title":"Serum levels of interleukin 6 (IL-6), oncostatin M, soluble IL-6 receptor, and soluble gp130 in patients with systemic sclerosis","volume":"25","author":"Hasegawa","year":"1998","journal-title":"J Rheumatol"},{"key":"2025120523561270000_71.7.620.45","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-6-96"},{"key":"2025120523561270000_71.7.620.46","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0025392","article-title":"Immunoglobulin free light chains are increased in hypersensitivity pneumonitis and idiopathic pulmonary fibrosis","volume":"6","author":"Groot Kormelink","year":"2011","journal-title":"PLoS One"},{"key":"2025120523561270000_71.7.620.47","doi-asserted-by":"publisher","DOI":"10.1002\/art.22847"},{"key":"2025120523561270000_71.7.620.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2015.03.014"},{"key":"2025120523561270000_71.7.620.49","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.3109\/0886022X.2015.1052980","article-title":"The association of serum-free light-chain levels with markers of renal function","volume":"37","author":"Erdem","year":"2015","journal-title":"Ren Fail"}],"container-title":["Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jclinpath-2017-204656","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T07:56:23Z","timestamp":1765007783000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jclinpath-2017-204656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,31]]},"references-count":49,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2018,7,18]]},"published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1136\/jclinpath-2017-204656"],"URL":"https:\/\/doi.org\/10.1136\/jclinpath-2017-204656","relation":{},"ISSN":["0021-9746","1472-4146"],"issn-type":[{"value":"0021-9746","type":"print"},{"value":"1472-4146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,31]]}}}