Human anti-CD38 autoantibodies raise intracellular calcium and stimulate insulin release in human pancreatic islets

Diabetes
Alessandro AntonelliE Ferrannini

Abstract

CD38 is involved in transmembrane signaling in many cell types; anti-CD38 autoantibodies have been described in diabetic patients. We tested whether human anti-CD38 antibodies possess signaling properties by measuring their ability to raise intracellular calcium ([Ca2+]i) using the fluo-3-acetoxymethyl ester method in a human-derived T-cell line (Jurkat T-cells, expressing high levels of surface CD38) and in dispersed human islet cells from normal donors. In Jurkat T-cells, 11 of 19 anti-CD38-positive sera raised [Ca2+]i (by > or =20% of baseline), whereas no [Ca2+]i-mobilizing activity was found in 27 anti-CD38-negative sera (chi2 = 20.5, P < 0.0001). In dispersed human islet cells, 5 of 11 anti-CD38-positive sera (and none of three anti-CD38-negative sera) raised [Ca2+]i significantly. When preincubated with Staphylococcus aureus protein A to remove IgG, anti-CD38-positive sera showed a 70 +/- 5% reduction in [Ca2+]i-mobilizing activity. Preincubation with CD38-transfected NIH-3T3 fibroblasts, but not with mock-transfected NIH-3T3 cells, abolished [Ca2+]i mobilization. In blocking experiments, preincubation with nonagonistic anti-CD38 monoclonal antibodies also prevented [Ca2+]i mobilization. In cultured human islets, anti-CD...Continue Reading

References

Jan 1, 1992·International Journal of Clinical & Laboratory Research·F MalavasiS Roggero
Aug 1, 1994·Cell Calcium·G A RutterC B Wollheim
Apr 19, 1996·Molecular and Cellular Endocrinology·D Mercan, W J Malaisse
Oct 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·K MehtaF Malavasi
Feb 24, 1997·Biochemical and Biophysical Research Communications·W J MalaisseT Katada
Feb 3, 1998·Diabetologia·M S Islam, P O Berggren
May 12, 1998·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M MorraF Malavasi
Mar 19, 1999·Biochemical and Biophysical Research Communications·R LupiR Navalesi
Mar 24, 1999·Journal of Leukocyte Biology·E Ferrero, F Malavasi
Nov 24, 1999·Nature Cell Biology·O A AdebanjoM Zaidi
Jun 2, 2000·Diabetes Care·P MarchettiR Navalesi

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Citations

Dec 18, 2001·Diabetes/metabolism Research and Reviews·B NazlielB Koçer
Dec 12, 2001·Clinical and Experimental Immunology·A AntonelliE Ferrannini
Dec 5, 2008·Molecular Medicine·Alberto L HorensteinFabio Malavasi
Feb 18, 2014·Cytokine & Growth Factor Reviews·Alessandro AntonelliPoupak Fallahi
Oct 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·James D Johnson, Stanley Misler
Jan 17, 2016·Autoimmunity Reviews·Carlo PerriconeYehuda Shoenfeld
Nov 10, 2014·Immunologic Research·Alessandro AntonelliPoupak Fallahi
Mar 18, 2006·Diabetes/metabolism Research and Reviews·Roberto Mallone, Paolo Cavallo Perin
Jan 13, 2006·Diabetic Medicine : a Journal of the British Diabetic Association·V SordiE Bonifacio
Jan 31, 2006·Biochemical and Biophysical Research Communications·Li SunMone Zaidi
Sep 1, 2015·Advances in Medical Sciences·Silvia Martina FerrariPoupak Fallahi
Nov 7, 2014·International Journal of Endocrinology·Poupak FallahiAlessandro Antonelli
Sep 28, 2006·Diabetes·James D JohnsonKenneth S Polonsky
Dec 3, 2014·Autoimmunity Reviews·Alessandro AntonelliPoupak Fallahi
Apr 11, 2018·The Journal of Biological Chemistry·Cheng FangYong Juan Zhao
Mar 13, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Li SunMone Zaidi
Dec 22, 2019·The Journal of Clinical Endocrinology and Metabolism·Poupak FallahiAlessandro Antonelli
Oct 28, 2004·Journal of Endocrinological Investigation·A Antonelli, E Ferrannini
Jan 15, 2020·Best Practice & Research. Clinical Endocrinology & Metabolism·Poupak FallahiAlessandro Antonelli
Sep 16, 2020·Chemical Reviews·Kylie A Agnew-Francis, Craig M Williams
Aug 10, 2021·Frontiers in Medicine·Jing XuDaisuke Koya

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