{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:20:36Z","timestamp":1761895236225},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,3,30]],"date-time":"2011-03-30T00:00:00Z","timestamp":1301443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background:\u2002<\/jats:bold> In Iceland, eight families have been identified with multiple cases of monoclonal gammopathies (MG) and other lymphoproliferative diseases. In one of these families with several cases of monoclonal gammopathy of undetermined significance (MGUS) and Waldenstr\u00f6ms macroglobulinemia, <jats:italic>in vitro<\/jats:italic> stimulation with poke\u2010weed mitogen revealed hyper\u2010responsive B cells showing increased immunoglobulin production in one\u2010third of disease\u2010free family members.<\/jats:p><jats:p><jats:bold>Design and methods:\u2002<\/jats:bold> In this study, the families were further traced and the list of names produced was compared with The Icelandic Cancer Registry (ICR) to find all recent cases of lymphoproliferative diseases. First\u2010degree relatives and descendants older than 20\u2003yrs of age (<jats:italic>n<\/jats:italic>\u2003=\u2003350) were selected for screening for paraprotein. Selected family members were tested for B\u2010cell hyper\u2010responsiveness and the lymphocyte phenotype was analysed by flow cytometry.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Comparison of the total list of 4370 family members with the ICR revealed 22 new cases and screening for serum paraprotein identified nine new cases of MG, eight being first\u2010degree relatives of known probands. Sixty cases of lymphoproliferative diseases are currently known within the eight families, five of them containing both IgG\/A and IgM disorders. Twelve hyper\u2010responders (HR) were identified in four families, eight from one family, of whom four were known already. Stimulated B cells from HR had a significantly higher proportion of CD27<jats:sup>+<\/jats:sup> memory\/plasma cells than controls.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> Identification of new affected family members by screening confirms a hereditary predisposition to B\u2010cell proliferative diseases. Contrary to most studies, IgG\/A and IgM disorders occurred together in five families. In four families, enhanced B\u2010cell responsiveness was found in healthy subjects clustered around cases.<\/jats:p>","DOI":"10.1111\/j.1600-0609.2011.01593.x","type":"journal-article","created":{"date-parts":[[2011,2,23]],"date-time":"2011-02-23T12:43:23Z","timestamp":1298465003000},"page":"396-404","source":"Crossref","is-referenced-by-count":8,"title":["Familial monoclonal gammopathy: hyper\u2010responsive B cells in unaffected family members"],"prefix":"10.1111","volume":"86","author":[{"given":"Hl\u00edf","family":"Steingr\u00edmsd\u00f3ttir","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helga K.","family":"Einarsd\u00f3ttir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vilhelm\u00edna","family":"Haraldsd\u00f3ttir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helga M.","family":"\u00d6gmundsd\u00f3ttir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,3,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.4065\/79.7.859"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2002.03589.x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11284"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0954-6820.1966.tb05453.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.5271\/sjweh.782"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.jom.0000083033.56116.c1"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00053156"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21745"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-8049(93)90188-L"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(78)90071-1"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0753-3322(02)00194-4"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-08-3449"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(11)61089-6"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2257.1998.00109.x"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197711)40:5<2094::AID-CNCR2820400518>3.0.CO;2-5"},{"key":"e_1_2_6_17_2","first-page":"226","article-title":"Familial occurrence of monoclonal gammapathies","volume":"28","author":"Youinou P","year":"1978","journal-title":"Biomedicine"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19891001)64:7<1554::AID-CNCR2820640734>3.0.CO;2-3"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1053\/sonc.2003.50063"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdj111"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(75)90333-2"},{"key":"e_1_2_6_22_2","first-page":"201","article-title":"Familial myeloma","volume":"100","author":"Boga M","year":"1973","journal-title":"Folia Haematol Int Mag Klin Morphol Blutforsch"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1159\/000209015"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0338-4535(85)80004-0"},{"key":"e_1_2_6_25_2","first-page":"891","article-title":"Familial Waldenstrom\u2019s macroglobulinaemia: a case report","volume":"51","author":"Getaz EP","year":"1977","journal-title":"S Afr Med J"},{"key":"e_1_2_6_26_2","first-page":"1932","article-title":"Family studies in Waldenstrom\u2019s macroglobulinaemia","volume":"110","author":"Kalff MW","year":"1966","journal-title":"Ned Tijdschr Geneeskd"},{"key":"e_1_2_6_27_2","first-page":"1363","article-title":"A case\u2013control and family study of Waldenstrom\u2019s macroglobulinemia","volume":"7","author":"Linet MS","year":"1993","journal-title":"Leukemia"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.3109\/02841869109092443"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0954-6820.1978.tb14874.x"},{"key":"e_1_2_6_30_2","first-page":"6263","article-title":"Risk of plasma\u2010cell and lymphoproliferative disorders among 14,621 first\u2010degree relatives of 4,458 patients with monoclonal gammopathy of undetermined significance (MGUS) in Sweden","volume":"113","author":"Landgren O","year":"2009","journal-title":"Blood"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-162768"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.3816\/CLM.2009.n.005"},{"key":"e_1_2_6_33_2","first-page":"66","article-title":"Familiality of benign and malignant paraproteinemias. 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