{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:24:33Z","timestamp":1777983873425,"version":"3.51.4"},"reference-count":28,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T00:00:00Z","timestamp":1746316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Scleroderma and Related Disorders"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Hypogammaglobulinemia is a condition that can be related to both primary and secondary immunodeficiencies. While the role of primary immunodeficiency in immune-mediated diseases is well known, its occurrence in systemic sclerosis is not reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>This study aims to describe the clinical features associated with hypogammaglobulinemia in a cohort of limited cutaneous systemic sclerosis patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We retrospectively reviewed medical records of systemic sclerosis patients from two Italian referral centres (2010\u20132024). Included patients had limited cutaneous systemic sclerosis and presented reduced serum concentrations of one or more Ig isotypes (IgG\u2009&lt;\u2009700\u2009mg\/dL, IgA\u2009&lt;\u200970\u2009mg\/dL or IgM\u2009&lt;\u200950\u2009mg\/dL) in at least two separate measurements. Patients with secondary causes of hypogammaglobulinemia were excluded. Data collected included demographics, clinical features, Ig levels, infection history and comorbidities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We identified 30 systemic sclerosis patients (93% female, mean age 62\u2009years) with limited cutaneous involvement and hypogammaglobulinemia. Most patients were positive for anti-centromere antibodies and received periodic intravenous infusions of prostaglandin analogues. No patient received immunosuppressive therapy. Median (interquartile range) serum IgG levels 519.5 (175) mg\/dL, median IgA 65.5 (48) mg\/dL and median IgM 71.5 (49) mg\/dL. Four patients who met the European Society for Immunodeficiencies (ESID) criteria for common variable immunodeficiency experienced recurrent infections and had associated immune-mediated diseases. Five patients had selective IgA deficiency, with frequent immune-mediated comorbidities (thyroiditis, Sj\u00f6gren\u2019s syndrome, arthritis, psoriasis). The other patients exhibited mild IgG deficiency without a significant infectious history.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This is the first study describing a cohort of patients with limited cutaneous systemic sclerosis and hypogammaglobulinemia. Our population presented a high prevalence of immune-mediated comorbidities but low infection rates. Further research is needed to explore the underlying mechanisms and clinical significance of hypogammaglobulinemia in these patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/23971983251333851","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T01:43:04Z","timestamp":1746409384000},"page":"494-501","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Hypogammaglobulinemia in patients affected by limited cutaneous systemic sclerosis: Case series and review of the literature"],"prefix":"10.1136","volume":"10","author":[{"given":"Maria Giovanna","family":"Danieli","sequence":"first","affiliation":[{"name":"Immunology of Rare Diseases and Transplants, Department of Internal Medicine, Marche University Hospital, Ancona, Italy"},{"name":"Postgraduate School of Allergy and Clinical Immunology, Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Mezzanotte","sequence":"additional","affiliation":[{"name":"UO Medicina Interna, Azienda Sanitaria Territoriale Pesaro Urbino, Fano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Paladini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy"},{"name":"Clinica Medica, Department of Internal Medicine, Marche University Hospital, Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9867-2360","authenticated-orcid":false,"given":"Devis","family":"Benfaremo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy"},{"name":"Clinica Medica, Department of Internal Medicine, Marche University Hospital, Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6403-6905","authenticated-orcid":false,"given":"Giuseppe","family":"Murdaca","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa, Genoa, Italy"},{"name":"Allergology and Clinical Immunology Unit, Ospedale San Bartolomeo, Sarzana, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0380-0105","authenticated-orcid":false,"given":"Gianluca","family":"Moroncini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy"},{"name":"Clinica Medica, Department of Internal Medicine, Marche University Hospital, Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,5,4]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.01.025"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.671503"},{"issue":"2","key":"e_1_3_3_4_2","first-page":"188","article-title":"Rituximab-associated hypogammaglobulinaemia in ANCA-associated vasculitis and connective tissue diseases: a longitudinal observational study","volume":"38","author":"Padoan R","year":"2020","unstructured":"Padoan R, Felicetti M, Gatto M, et al. Rituximab-associated hypogammaglobulinaemia in ANCA-associated vasculitis and connective tissue diseases: a longitudinal observational study. Clin Exp Rheumatol 2020; 38(2): 188\u2013194.","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30933-9"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10010163"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/2397198319870667"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.38098"},{"issue":"7","key":"e_1_3_3_9_2","first-page":"1573","article-title":"Criteria for the classification of early systemic sclerosis","volume":"28","author":"LeRoy EC","year":"2001","unstructured":"LeRoy EC, Medsger TA. Criteria for the classification of early systemic sclerosis. 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