{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T22:39:54Z","timestamp":1762641594514,"version":"3.40.3"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Common variable immunodeficiency (CVID) is a disease that is characterized primarily by low levels of serum Igs, resulting in a high incidence of infections. It also has been associated with impaired B cell signaling via TLR9 and reduced serum levels of vitamin A. Given the established link between vitamin A deficiency and increased susceptibility to infections, we investigated the ability of the vitamin A metabolite all-trans retinoic acid (RA) to restore the defective immune responses in CVID-derived B cells activated through the TLRs TLR9 and RP105. We demonstrate that RA almost normalizes proliferation and IL-10 secretion in patient-derived B cells. IgG secretion is also partially restored, but to a more moderate extent. This can be explained by impaired RA-mediated isotype switching in TLR9\/RP105-stimulated CVID-derived B cells owing to reduced induction of activation-induced deaminase. Accordingly, these B cells secreted higher levels of IgM than did normal B cells, and RA augmented IgM secretion. The ability of RA to improve critical immune parameters in CVID-derived B cells stimulated through TLR9 and RP105 support the possibility of combining RA with TLR stimulation for the treatment of CVID.<\/jats:p>","DOI":"10.4049\/jimmunol.1300213","type":"journal-article","created":{"date-parts":[[2013,9,5]],"date-time":"2013-09-05T04:46:35Z","timestamp":1378356395000},"page":"3624-3633","source":"Crossref","is-referenced-by-count":18,"title":["Retinoic Acid Improves Defective TLR9\/RP105-Induced Immune Responses in Common Variable Immunodeficiency\u2013Derived B Cells"],"prefix":"10.1093","volume":"191","author":[{"given":"Randi L","family":"Indrev\u00e6r","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo , N-0317 Oslo,","place":["Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristine L","family":"Holm","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo , N-0317 Oslo,","place":["Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e5l","family":"Aukrust","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, University of Oslo , N-0424 Oslo,","place":["Norway"]},{"name":"Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, University of Oslo , N-0424 Oslo,","place":["Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liv T","family":"Osnes","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Rikshospitalet, Oslo University Hospital , N-0424 Oslo,","place":["Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elin H","family":"Naderi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo , N-0317 Oslo,","place":["Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00f8rre","family":"Fevang","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, University of Oslo , N-0424 Oslo,","place":["Norway"]},{"name":"Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, University of Oslo , N-0424 Oslo,","place":["Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi K","family":"Blomhoff","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo , N-0317 Oslo,","place":["Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,10,1]]},"reference":[{"key":"2025032405413579100_r1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1182\/blood-2010-01-254417","article-title":"How I treat common variable immune deficiency","volume":"116","author":"Cunningham-Rundles","year":"2010","journal-title":"Blood"},{"key":"2025032405413579100_r2","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1182\/blood-2011-09-377945","article-title":"Morbidity and mortality in common variable immune deficiency over 4 decades","volume":"119","author":"Resnick","year":"2012","journal-title":"Blood"},{"key":"2025032405413579100_r3","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1006\/clim.1999.4725","article-title":"Common variable immunodeficiency: clinical and immunological features of 248 patients","volume":"92","author":"Cunningham-Rundles","year":"1999","journal-title":"Clin. 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