{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T02:18:30Z","timestamp":1794363510075,"version":"4.9.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T00:00:00Z","timestamp":1589932800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T00:00:00Z","timestamp":1589932800000},"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><jats:p>Purpose: To characterize rheumatological manifestations of GATA2 deficiency. Methods: Single-center, retrospective review of 157 patients with GATA2 deficiency. Disease course, laboratory results, and imaging findings were extracted. In-person rheumatological assessments were performed on selected, available patients. A literature search of four databases was conducted to identify additional cases. Results: Rheumatological findings were identified in 28 patients, out of 157 cases reviewed (17.8%). Twenty-two of those patients (78.6%) reported symptom onset prior to or in conjunction with the molecular diagnosis of GATA2 deficiency. Notable rheumatological manifestations included: piezogenic pedal papules (PPP), joint hyperextensibility, early onset osteoarthritis, ankylosing spondylitis, and seronegative erosive rheumatoid arthritis. In peripheral blood of patients with rheumatological manifestations and GATA2 deficiency, CD4+ CD3+ helper T cells and na\u00efve CD3+ CD4+ CD62L+ CD45RA+ helper T cell subpopulation fractions were significantly lower, while CD8+ cytotoxic T cell fractions were significantly higher, compared to those without rheumatological manifestations and with GATA2 deficiency. No changes in CD19, CD3, or NK populations were observed. Conclusion: GATA2 deficiency is associated with a broad spectrum of rheumatological disease manifestations. Low total helper T lymphocyte proportions and low na\u00efve helper T cell proportions are associated with those most at risk of overt rheumatological manifestations. Further, PPP and joint hyperextensibility may explain some of the nonimmunologically-mediated joint problems encountered in patients with GATA2 deficiency. This catalogue suggests that rheumatological manifestations and immune dysregulation are relatively common in GATA2 deficiency.<\/jats:p>","DOI":"10.1038\/s41598-020-64852-1","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T10:03:13Z","timestamp":1589968993000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A Panoply of Rheumatological Manifestations in Patients with GATA2 Deficiency"],"prefix":"10.1038","volume":"10","author":[{"given":"Abhimanyu A.","family":"Amarnani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katlin R.","family":"Poladian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz E.","family":"Marciano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine R.","family":"Daub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra G.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia A.","family":"Livinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy P.","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy L.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara M.","family":"Kenney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele N.","family":"Avila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Holland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Katz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,20]]},"reference":[{"key":"64852_CR1","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1182\/blood-2013-07-515528","volume":"123","author":"MA Spinner","year":"2014","unstructured":"Spinner, M. A. et al. GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. Blood 123, 809\u2013821 (2014).","journal-title":"Blood"},{"key":"64852_CR2","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.3324\/haematol.2017.181909","volume":"103","author":"J Donadieu","year":"2018","unstructured":"Donadieu, J. et al. Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients. haematologica 103, 1278\u20131287 (2018).","journal-title":"haematologica"},{"key":"64852_CR3","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1111\/imr.12725","volume":"287","author":"EM Mace","year":"2019","unstructured":"Mace, E. M. & Orange, J. S. Emerging insights into human health and NK cell biology from the study of NK cell deficiencies. Immunological reviews 287, 202\u2013225 (2019).","journal-title":"Immunological reviews"},{"key":"64852_CR4","doi-asserted-by":"publisher","first-page":"3715","DOI":"10.1182\/blood-2011-06-365049","volume":"118","author":"J Cuellar-Rodriguez","year":"2011","unstructured":"Cuellar-Rodriguez, J. et al. Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency. Blood 118, 3715\u20133720, https:\/\/doi.org\/10.1182\/blood-2011-06-365049 (2011).","journal-title":"Blood"},{"key":"64852_CR5","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1007\/s10067-015-2905-2","volume":"34","author":"JA Johnson","year":"2015","unstructured":"Johnson, J. A., Yu, S. S., Elist, M., Arkfeld, D. & Panush, R. S. Rheumatologic manifestations of the \u201cMonoMAC\u201d syndrome. a systematic review. Clinical Rheumatology 34, 1643\u20131645, https:\/\/doi.org\/10.1007\/s10067-015-2905-2 (2015).","journal-title":"Clinical Rheumatology"},{"key":"64852_CR6","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1182\/blood-2009-03-208629","volume":"115","author":"DC Vinh","year":"2010","unstructured":"Vinh, D. C. et al. Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood 115, 1519\u20131529 (2010).","journal-title":"Blood"},{"key":"64852_CR7","doi-asserted-by":"crossref","unstructured":"Bigley, V. & Matthew, C. Dendritic cell, monocyte, B and NK lymphoid deficiency defines the lost lineages of a new GATA-2 dependent myelodysplastic syndrome. Haematologica, 1081\u20131083 (2011).","DOI":"10.3324\/haematol.2011.048355"},{"key":"64852_CR8","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1084\/jem.20101459","volume":"208","author":"V Bigley","year":"2011","unstructured":"Bigley, V. et al. The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency. Journal of Experimental Medicine 208, 227\u2013234 (2011).","journal-title":"Journal of Experimental Medicine"},{"key":"64852_CR9","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1007\/s00431-012-1715-7","volume":"171","author":"H Ishida","year":"2012","unstructured":"Ishida, H. et al. GATA-2 anomaly and clinical phenotype of a sporadic case of lymphedema, dendritic cell, monocyte, B- and NK-cell (DCML) deficiency, and myelodysplasia. European Journal of Pediatrics 171, 1273\u20131276, https:\/\/doi.org\/10.1007\/s00431-012-1715-7 (2012).","journal-title":"European Journal of Pediatrics"},{"key":"64852_CR10","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1093\/cid\/cit368","volume":"57","author":"JF Camargo","year":"2013","unstructured":"Camargo, J. F. et al. MonoMAC syndrome in a patient with a GATA2 mutation: Case report and review of the literature. Clinical Infectious Diseases 57, 697\u2013699, https:\/\/doi.org\/10.1093\/cid\/cit368 (2013).","journal-title":"Clinical Infectious Diseases"},{"key":"64852_CR11","doi-asserted-by":"publisher","first-page":"2766","DOI":"10.3389\/fimmu.2018.02766","volume":"9","author":"S Prader","year":"2018","unstructured":"Prader, S. et al. Life-threatening primary varicella zoster virus infection with hemophagocytic lymphohistiocytosis-like disease in GATA2 haploinsufficiency accompanied by expansion of double negative T-lymphocytes. Frontiers in immunology 9, 2766 (2018).","journal-title":"Frontiers in immunology"},{"key":"64852_CR12","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1111\/bjd.15548","volume":"178","author":"A Polat","year":"2018","unstructured":"Polat, A. et al. Skin manifestations among GATA2-deficient patients. British Journal of Dermatology 178, 781\u2013785, https:\/\/doi.org\/10.1111\/bjd.15548 (2018).","journal-title":"British Journal of Dermatology"},{"key":"64852_CR13","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1007\/s10875-018-0551-6","volume":"38","author":"L Damian","year":"2018","unstructured":"Damian, L. et al. Pseudo-Sarcoidosis Revealing MonoMAC Syndrome. Journal of Clinical Immunology 38, 739\u2013741, https:\/\/doi.org\/10.1007\/s10875-018-0551-6 (2018).","journal-title":"Journal of Clinical Immunology"},{"key":"64852_CR14","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1182\/blood-2013-07-517151","volume":"123","author":"RE Dickinson","year":"2014","unstructured":"Dickinson, R. E. et al. The evolution of cellular deficiency in GATA2 mutation. Blood 123, 863\u2013874 (2014).","journal-title":"Blood"},{"key":"64852_CR15","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1002\/acr.23870","volume":"71","author":"S Ringold","year":"2019","unstructured":"Ringold, S. et al. American College of Rheumatology\/Arthritis Foundation guideline for the treatment of juvenile idiopathic arthritis: therapeutic approaches for non\u2010systemic polyarthritis, sacroiliitis, and enthesitis. Arthritis care & research 71, 717\u2013734 (2019).","journal-title":"Arthritis care & research"},{"key":"64852_CR16","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.ecl.2016.09.005","volume":"46","author":"BC Silva","year":"2017","unstructured":"Silva, B. C. & Leslie, W. D. Trabecular bone score: a new DXA\u2013derived measurement for fracture risk assessment. Endocrinology and Metabolism Clinics 46, 153\u2013180 (2017).","journal-title":"Endocrinology and Metabolism Clinics"},{"key":"64852_CR17","doi-asserted-by":"publisher","first-page":"47785","DOI":"10.1074\/jbc.M309482200","volume":"278","author":"X Han","year":"2003","unstructured":"Han, X., Boyd, P. J., Colgan, S., Madri, J. A. & Haas, T. L. Transcriptional up-regulation of endothelial cell matrix metalloproteinase-2 in response to extracellular cues involves GATA-2. Journal of Biological Chemistry 278, 47785\u201347791 (2003).","journal-title":"Journal of Biological Chemistry"},{"key":"64852_CR18","doi-asserted-by":"publisher","first-page":"R57","DOI":"10.1186\/ar4224","volume":"15","author":"A Rastogi","year":"2013","unstructured":"Rastogi, A., Kim, H., Twomey, J. D. & Hsieh, A. H. MMP-2 mediates local degradation and remodeling of collagen by annulus fibrosus cells of the intervertebral disc. Arthritis research & therapy 15, R57 (2013).","journal-title":"Arthritis research & therapy"},{"key":"64852_CR19","doi-asserted-by":"publisher","unstructured":"Tolkachov, A. et al. Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone. Mol Cell Biol 38, https:\/\/doi.org\/10.1128\/mcb.00599-17 (2018).","DOI":"10.1128\/mcb.00599-17"},{"key":"64852_CR20","doi-asserted-by":"publisher","first-page":"4692","DOI":"10.1128\/mcb.05979-11","volume":"31","author":"W Wei","year":"2011","unstructured":"Wei, W. et al. Osteoclast progenitors reside in the peroxisome proliferator-activated receptor gamma-expressing bone marrow cell population. Mol Cell Biol 31, 4692\u20134705, https:\/\/doi.org\/10.1128\/mcb.05979-11 (2011).","journal-title":"Mol Cell Biol"},{"key":"64852_CR21","doi-asserted-by":"publisher","first-page":"4706","DOI":"10.1128\/mcb.05980-11","volume":"31","author":"W Wei","year":"2011","unstructured":"Wei, W. et al. Biphasic and dosage-dependent regulation of osteoclastogenesis by beta-catenin. Mol Cell Biol 31, 4706\u20134719, https:\/\/doi.org\/10.1128\/mcb.05980-11 (2011).","journal-title":"Mol Cell Biol"},{"key":"64852_CR22","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/j.jid.2019.01.006","volume":"139","author":"S Moos","year":"2019","unstructured":"Moos, S., Mohebiany, A. N., Waisman, A. & Kurschus, F. C. Imiquimod-Induced Psoriasis in Mice Depends on the IL-17 Signaling of Keratinocytes. Journal of Investigative Dermatology 139, 1110\u20131117 (2019).","journal-title":"Journal of Investigative Dermatology"},{"key":"64852_CR23","doi-asserted-by":"crossref","unstructured":"Machler, B., Mark, N., Patel, U. & Levine, V. Imiquimod induced psoriasis: A case report, review of the literature, and pathophysiologic mechanism: P3313. Journal of the American Academy of Dermatology 64 (2011).","DOI":"10.1016\/j.jaad.2010.09.606"},{"key":"64852_CR24","doi-asserted-by":"publisher","first-page":"e55570","DOI":"10.1371\/journal.pone.0055570","volume":"8","author":"F Bugault","year":"2013","unstructured":"Bugault, F. et al. Altered responses to homeostatic cytokines in patients with idiopathic CD4 lymphocytopenia. PloS one 8, e55570 (2013).","journal-title":"PloS one"},{"key":"64852_CR25","doi-asserted-by":"publisher","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 CD21low B cell population in the peripheral blood of patients with SLE. Clinical immunology 113, 161\u2013171 (2004).","journal-title":"Clinical immunology"},{"key":"64852_CR26","doi-asserted-by":"crossref","unstructured":"Thorarinsdottir, K. et al. CD 21\u2010\/low B cells associate with joint damage in rheumatoid arthritis patients. Scandinavian journal of immunology, e12792 (2019).","DOI":"10.1111\/sji.12792"},{"key":"64852_CR27","doi-asserted-by":"publisher","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\u2212\/low B cells in Sj\u00f6gren\u2019s syndrome\u2013associated lymphoproliferation. Arthritis & Rheumatism 65, 1085\u20131096 (2013).","journal-title":"Arthritis & Rheumatism"},{"key":"64852_CR28","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1046\/j.1365-2249.2000.01379.x","volume":"122","author":"H Illges","year":"2000","unstructured":"Illges, H., Braun, M., Peter, H. & Melchers, I. Reduced expression of the complement receptor type 2 (CR2, CD21) by synovial fluid B and T lymphocytes. Clinical & Experimental Immunology 122, 270\u2013276 (2000).","journal-title":"Clinical & Experimental Immunology"},{"key":"64852_CR29","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1136\/annrheumdis-2013-204116","volume":"74","author":"L Yeo","year":"2015","unstructured":"Yeo, L. et al. Expression of FcRL4 defines a pro-inflammatory, RANKL-producing B cell subset in rheumatoid arthritis. Annals of the rheumatic diseases 74, 928\u2013935 (2015).","journal-title":"Annals of the rheumatic diseases"},{"key":"64852_CR30","doi-asserted-by":"crossref","unstructured":"Mensah, K. A. et al. Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis. Science Translational Medicine 11 (2019).","DOI":"10.1126\/scitranslmed.aaw4626"},{"key":"64852_CR31","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.autrev.2014.10.012","volume":"14","author":"CR Grant","year":"2015","unstructured":"Grant, C. R., Liberal, R., Mieli-Vergani, G., Vergani, D. & Longhi, M. S. Regulatory T-cells in autoimmune diseases: challenges, controversies and\u2014yet\u2014unanswered questions. Autoimmunity reviews 14, 105\u2013116 (2015).","journal-title":"Autoimmunity reviews"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-64852-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-64852-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-64852-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T09:16:01Z","timestamp":1696151761000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-64852-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,20]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["64852"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-64852-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,20]]},"assertion":[{"value":"31 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8305"}}