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Betty Diamond

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Betty Diamond (b. May 11, 1948, Hartford, Ct, USA) is a scientist studying systemic lupus erythematosus, an autoimmune disease that affects many organs. She heads a research center at The Feinstein Institute for Medical Research. Dr Diamond’s research has focused on the induction and pathogenicity of anti-DNA antibodies in Systemic Lupus Erythematosus.Dr. Diamond's research focuses on how foreign antigens react with and elicit pathogenic anti-DNA antibodies in patients with systemic lupus. [1] She identified the first and still most clinically significant and common idiotype marker on anti-DNA antibodies in patients with lupus,[2] and discovered that anti-DNA antibodies in patients and mice shared characteristics with antibodies to pneumococcal polysaccharide. This finding led her to propose that infections could cause exacerbations of the disease. Dr. Diamond showed that a single base change in a protective anti-pneumococcal antibody could convert it into a potentially pathogenic anti-DNA antibody. She also found that a peptide that binds to 50% of anti-DNA antibodies in lupus patients and mice shares an epitope on glutamate receptors of the brain and destroys neurons. Antibodies against the epitope are present in the cerebrospinal fluid and in brain tissue of patients with neuropsychiatric lupus. Her work provides a mechanism for aspects of neuropsychiatric lupus, and more generally for acquired changes in cognition and behavior. Dr. Diamond also studies the role that hormones may play in the development of lupus.[3]


Dr. Diamond’s primary interests are in the mechanisms of central and peripheral tolerance of autoreactive B cells, [4] and the defects in these mechanisms that are present in autoimmune disease. Her laboratory has been studying the regulation of DNA-reactive B cells [5] and the role of hormones and antigen in inducing autoimmunity. In a mouse transgenic for the heavy chain of a pathogenic anti-DNA antibody, elevated concentrations of both estradiol and prolactin break tolerance, cause high affinity anti-DNA B cells that are normally deleted in the bone marrow to be activated and contribute to the expressed antibody repertoire.

Dr. Diamond’s laboratory has also developed a model of SLE induced by immunization with a peptide mimetope of DNA. This model is of interest because it demonstrates that pathogenic autoreactivity can be induced in a non-spontaneously autoimmune host. Furthermore, mouse strains differ in their susceptibility to this antigen-induced model of SLE. The laboratory has performed genetic analyses to identify 3 chromosomal loci in BALB/c mice important in conferring disease susceptibility.[6].

Dr. Diamond continues to study anti-DNA antibodies from patients with SLE, having developed a methodology for the identification of DNA-reactive B cells within the entire B repertoire. Furthermore, recent studies from her laboratory show a lack of activation induced upregulated of FcRIIb, an inhibitory receptor, on memory B cells of SLE patients. The Diamond laboratory demonstrated that a subset of anti-DNA antibodies cross-reacts with the NMDA receptor. [7]. These antibodies can mediate neuronal apoptosis in the hippocampus leading to a memory deficit or in the amygdala leading to a behavioral alteration. These studies show that lupus antibodies can cause aspects of neuropsychiatric lupus in a non-inflammatory fashion and create a paradigm for antibody-mediated changes in brain function in many conditions.


Honors

Dr. Diamond received the Outstanding Investigator Award of the ACR in 2001, the Lee Howley Award from the Arthritis Foundation in 2002, and the Recognition Award from the National Association of MD-PhD Programs in 2004. Dr. Diamond is on the Scientific Council of NIAMS and the Board of Directors of the American College of Rheumatology. Dr. Diamond is a past chair of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Board of Scientific Councilors. She is currently a member of the NIAMS Council. She is on the Council of the American Association of Immunologists, and President-elect for the 2009-2010 term. She is on the Board of Directors of the American College of Rheumatology, a fellow of the AAASand a member of the Institute of Medicine, elected in 2006. She is a Professor of The Elmezzi Graduate School of Molecular Medicine.

References

  1. ^ Nature Medicine 7, 1189 - 1193 (2001) doi:10.1038/nm1101-1189
  2. ^ Journal of Immunology, 133;1852
  3. ^ Nature Reviews Immunology 9:449-456 (2009)
  4. ^ J. Immunol 176:3311
  5. ^ J. Immunol Methods 338:79-84
  6. ^ J. Exp. Med. 173:287
  7. ^ Proc. Natl. Acad. Sci. 103:19854-19859

Key Publications

  • Mackay, M., Stanevsky, A., Wang, T., Aranow, C., Li, M., Koenig, S., Ravetch, JV and Diamond B. Selective dysregulation of the FC (gamma) llB receptor on memory B cells in SLE. J. Exp. Med,2006; 203:2157-2164
  • Kowal C, DeGiorgio LA, Lee JY, Edgard ME, Huerta PT, Volpe BT and Diamond B. Human lupus autoantibodies against NMDA receptors mediate cognitive impairment. Proc. Natl. Acad. Sci. 2006; 103:19854-19859
  • Looney, RJ., Diamond, B. Holers, VM., Levesque, MC., Moreland, L., Nahm, MH and St. Clair W. Guidelines for assessing immunocompetency in clinical trials for autoimmune disease. Clinical Imunol. 2007; 123:235-243
  • Grimaldi, C., Nashi, E., Venkatesh, J., and Diamond, B. B cell hyporesponsiveness and autoimmunity: a new paradigm. Adv. Exp. Med. Biol. 2007596:181-190
  • Yelton, D.E., Diamond, B.A., Kwan, S.P. and Scharff, M.D. Fusion of mouse myeloma and spleen cells. Current topics in Micro. and Immuno., 81:1 (1978)
  • Bloom, B.R., Diamond, B.A., Muschel, R., Rosen, N., Schneck, J., Damiani, G., Rosen, O. and Scharff, M.D. Genetics approaches to the mechanism of macrophage function. Fed. Proc. 37:2765 (1978)
  • Yelton, D.E., Margulies, D.H., Diamond, B. and Scharff, M.D. Plasmacytomas and hybridomas: Development and applications. (eds. Kennet, R.H., McKearn, T.J. and Bechtol, K.B.) Plenum Press, N.Y. and London. (1980)
  • Diamond, B. and Birshtein, B.K. Binding of variant immunoglobulin molecules to Fc receptors on macrophages. International Workshop on the heteogeneity of Mononuclear Phagocytes. (1980)
  • Diamond, B., Yelton, D. and Scharff, M.D. Monoclonal antibodies: A new technology for producing serological reagents. New England J. of Med., 304:1344. (1981)
  • Diamond, B., Campbell, R., Schneck, N.M. and Birshtein, B.K. Cyanogen bromide fragments of mouse IgG2a and IgG2b which bind to their Fc receptors on mouse macrophages. Protides of the Biological Fluids. 29:415:418. (1981)
  • Diamond, B. and Birshtein, B. Identification and fine specificity of Fc receptor on mouse macrophages in Heterogeneity of Mononuclear Phagocytes. (eds. Othmar Forster and Maurice Landy) Academic Press, London (1981)
  • Diamond, B. and Scharff, M.D. Monoclonal antibodies. J.A.M.A. 248:3165. (1982)
  • Diamond, B. Macrophages in the immune response. In: Liver: Biology and Pathobiology. (ed. Irwin Arias) Raven Press, N.Y. p. 525 (1982)
  • Diamond, B. and Solomon, G. Monoclonal antibody which recognizes anti-DNA antibodies in patients with systemic lupus. Proc. of N.Y. Acad. of Sci. 418:379. (1983)
  • Diamond, B., Chien, N. and Scharff, M.D. Somatic mutation alters affinity and specificity. Annales Immunol. 136C:259. (1985)
  • Scharff, M., Chien, N., Giusti, A.M., Zack, D. and Diamond, B. Single amino acid substitutions causes changes in antibody affinity and specificity. Immune Recognition of protein Antigens 44-47. (1985)
  • Nagata-Takeuchi, Y., Ding, G., Bloom, B.R. and Diamond, B. Production of human monocyte cell lines by DNA transfection. Progress in Leukocyte Biology Vol. 4, In: Macrophage Biology. (eds. M. Kojima and S. Reichard) (1986)
  • Davidson, A., Halpern, R. and Diamond, B. Speculation on the role of somatic mutation in the generation of anti-DNA antibodies. Annals of the N.Y. Acad. of Sci. 475:174. (1986)
  • Chien, N., Giusti, A.M., Zack, D., French, D., Shin, S.U., Diamond, B. and Scharff, M.D. Impact of somatic mutation on antibody affinity and specificity. Mt. Sinai J. of Med. 53:181. (1986)
  • Davidson, A., Chien, N., Frank, L., Halpern, R., Snapper, S., Zupko, K. and Diamond, B. Use of anti-idiotypic antibodies to explore genetic mechanisms of production of anti-DNA antibodies. J. Cell Immunol. 99:44. (1986)
  • Halpern, R., Davidson, A. and Diamond, B. Analysis of anti-DNA antibodies in SLE by a monoclonal anti-idiotype. Einstein Quarterly J. Bio. Med. 4:1
  • Schwarzbaum, S., Chang, M-d. Y. and Diamond, B. The study of I-E mutants. Einstein Quarterly 4:99. (1986)
  • Davidson, A., Shefner, R., Chien, N. and B. Diamond. Explorations into the role of somatic mutation in the generation of anti-DNA antibodies. Ann. Inst. Pasteur/Immunol. 137D:159. (1986)
  • Davidson, A., Shefner, R., Livneh, A. and Diamond, B. The role of somatic mutation of immunoglobulin genes in autoimmunity. Ann. Rev. Immunol. 5:85. (1987)
  • Davidson, A., Livneh, A., Manheimer-Lory, A., Shefner, R., Katz, J.B., Sewell, K-L. and Diamond, B. Idiotypic analyses of anti-DNA antibodies in lupus and monoclonal gammopathy. Ann. Inst. Pasteur/Immunol. 139:645.
  • Davidson, A., Shefner R. and Diamond, B. Studies on the role of somatic mutation in the generation of anti-DNA antibodies. Mono. in Allergy 22:31. (1987)
  • Behar, S.M., Fischer, B., Diamond, B. and Scharff, M.D. Variable region gene utilization and environment antigens in autoimmunity. Mono. in Allergy. 24:297. (1988)
  • Davidson, A. and Diamond, B. The roles of anti-idiotypes in understanding the pathogenesis of SLE in Inflammatory Bowel Disease. (ed. R.P. MacDermott) Elsevier (1988)
  • Behar, S.M., Corbet, S., Diamond, B. and Scharff, M.D. The molecular origin of anti-DNA antibodies. International Reviews of Immunol. 5:23. (1989)
  • Behar, S.M., Chien, N.C., Corbet, S., Diamond, B., Getzoff, E.D., Lustgarten, D., Roberts, V.A., Scharff, M.D. and Shin, S-U. The impact of somatic mutation on the S107(T15) heavy chain V region of antibodies reactives with self and non-self. Cold Spring Harbor Symposium. Vol. LIV: pp. 921-931. (1989)
  • Shefner, R., Manheimer-Lory, A., Davidson, A., Paul, E., Aranow, C., Katz, J. and Diamond, B. Idiotypes in SLE: Clues for understanding etiology and pathogenicity. Chem. Immunol. 48:82. (1990)
  • Paul, E., Manheimer-Lory, A. Livneh, A., Solomon, A., Aranow, C., Ghossein, C., Shefner, R., Offen, D., Pillinger, M. and Diamond, B. Pathogenic anti-DNA Antibodies in SLE: Idiotypic families and genetic origins. International Reviews of Immunology. 5:295. (1990)
  • Zouali, M. and Diamond, B. Idiotype-mediated intervention in system lupus erythematosus. J. Autoimmunity 3:381. (1990)
  • Diamond, B., Katz, J.B., Paul, E., Aranow, C., Lustgarten, D. and Scharff, M.D. The role of somatic mutation in the pathogenic anti-DNA response. Ann. Rev. Immunol. 10:731. (1992)
  • Aranow, C., Paul, E. and Diamond, B. The structure and derivation of antibodies and autoantibodies in Dubois systemic lupus erythematosus. 4th edition, ed. C. Wallace and B. Hahn. University of Southern California Press.
  • Bloom, B., Salgame, P. and Diamond, B. Revisiting and revising suppressor T cells. Immunology Today 13:4pg. 131. (1992)
  • Diamond, B. and Rauch, J. An Idiotype Systems Update. Lupus. 1:323-324. (1992)
  • Diamond, B. Anti-DNA antibodies in SLE. Lupus News 13:3 pg. 7 (1993)
  • Manheimer-Lory, A., Irigoyen, M., Gaynor, B., Monhian, R., Splaver, A. and Diamond, B. Analysis of VkI and VlII light chain genes in the expressed B cell repertoire. Annals. of the N.Y. Acad. of Sci. Vol. 764:301-311. (1995)
  • Kuo, P., Michael,D., Tadmor, B. and Diamond, B. Generation and regulation of cell autoreactivity arising in the periphery. Mechanisms of Lymphocyte Activation and Immune Regulation VI, Plenum Press, N.Y. (1996)
  • Spatz, L., Iliev, A., Saenko, V., Jones, L., Irigoyen, M., Manheimer-Lory, A., Gaynor, B., Putterman, C., Bynoe, M., Kowal, C., Kuo, P., Newman, J. and Diamond, B. Studies on the structure, regulation and pathogenic potential of anti-dsDNA antibodies. Methods: Companion to methods in Enzymology 11: 70-78. (1997)
  • Putterman, C., Kuo, P., and Diamond, B. The structure and derivation of antibodies and autoantibodies. in Dubois' Systemic Lupus Erythematosus, 5th ed., BH Hahn, DJ Wallace (editors). Williams and Wilkins Medical Publishers, Baltimore. (1997)
  • Kuo, P., Kowal, C., Tadmor, B., and Diamond B. Microbial Antigens Can Elicit Autoantibody Production. A Potential Pathway to Autoimmune Diease. N.Y. Acad. of Sciences. Annals. of the N.Y. Acad. of Sci. Vol. 815:230-236. (1997)
  • Diamond, B., and Eilat, D. DNA antibodies: focus on the light chain. Lupus. 6:315- 316. (1997)
  • Spatz, L., IIiev, A., Saenko, V., Jones, L., Irigoyen, M., Manheimer-Lory, A., Gaynor, B., Putterman, C., Bynoe, M., Kowal, C., Kuo, P., Newman, J., and Diamond, B. Studies on the Structure, Regulation, and Pathogenic Potential of Anti-dsDNA antibodies. Methods. 11:70-78. (1997)
  • Newman, J., and Diamond, B. The Anti-DNA Response in Lupus. ed., Tsokos and Kammer (editors). Humana Press Inc. Chapter 27:429-447. (1999)
  • Zandman-Goddard, G., and Diamond, B. Autoantibodies: Their Induciton and Pathogenicity in Inflammation: Basic Principles and Clinical Correlates. 3rd Ed., Chapter 59 Editors, Gallin and Snyderman. Lippincott Williams & Wilkins. (1999)
  • Khalil, M., Spatz, L., and Diamond, B. Anti-DNA Antibodies. Systemic Lupus Erythematosus. 3rd ed (editor) Lahita, R.G. Academic press, Inc. 197-217. (1999)
  • Grimaldi, C., and Diamond, B. B Cells. Ruddy S, Harris, ED Jr, Sledge, CB (eds.) in Kelly’s Textbook of Rheumatology, WB Saunders Company, Philadelphia, pp. 131-149. (2000)
  • Kowal, C., and Diamond, B. Mimicry between DNA, Carbohydrates, and Peptides: Implications in Systemic Lupus Erythematosus. Molecular Mimicry, Microbes and Autoimmunity. (editors) M.W. Cunningham and R.S. Fujinami. ASM press. Chapter 10:127-141. (2000)
  • Davidson, A., and Diamond, B. Autoimmune Diseases. New England J. of Medicine. 345:340-351. (2001).
  • Diamond, B. and Lipsky, P. Autoimmunity and Autoimmune Diseases. Harrison’s Principles of Internal Medicine 15th ed., Braunwald, Fauci, Kasper, Hauser, Longo, Jameson, McGraw Hill. New York (2001).
  • Peeva, E., Putterman, C. and Diamond, B. The structure and derivation of antibodies and autoantibodies in Dubois’ Systemic Lupus Erythematsous 6th ed Hahn, B.H.,Wallace, D.J.,(ed) Williams and Wilkins Medical Publishers 391-414 (2001).
  • Diamond, B., Bluestone, J., and Wofsy, D. The immune tolerance network and rheumatic disease: immune tolerance comes to the clinic. Arthritis & Rheumatism 44: 1730 (2001).
  • Davidson, A., Konstantinov, K., and Diamond, B. Targeting B cells. Targeted therapies in Rheumatology; Biological Therapy in Rheumatology, Josef Smolen and Peter Lipsky (eds.), Martin Dunitz Publishers, The Livery House. Vol 2 pp 23-42 (2002).
  • Peeva E. and Diamond B. Chapter Anti-DNA Antibodies: Structure, Assembly, and Diversity Systemic Lupus Erythematosus, 4th edition. Ed. Lahita R. (2002)
  • Diamond, B. Speculations on the Immunogenicity of Self Proteins. Immunogenicity of Therapeutic Biological Products. Brown F., Mire-Sluis, AR. (eds) Developments in Biologicals, vol 112 pp 29-34 (2003)
  • Estrada, SCK., Grimaldi, CM., Peeva, E., and Diamond, B. The role of estrogen and prolactin in the induction of SLE. Frontiers in Autoimmunity: Fundamental Aspects and Clinical perspectives; NATO Science Series: Life and Behavioral Sciences (series I) M. Zouali (ed) IOS Press. Vol 354 pp372 (2003).
  • Grimaldi C, Peeva E. and Diamond, B. Sex hormones and systemic lupus erythematosus, Chrousos, G and Geenen, V (eds.) in Neuroimmunoendocrinology, Marcel Dekker, New York, (2004) pp.
  • Caton, M. and Diamond, B. Using peptide mimetopes to elucidate anti-polysaccharide and anti-nucleic acid humoral responses. Cell Mol. Bio. 49:255-262 (2003).
  • Diamond, B. Speculations on the Immunogenicity of self proteins. Dev. Bio. 112:29-34 (2003).
  • Diamond, B. and Volpe, B. On the track of neuropsychiatric lupus. Arthritis Rheum. 48:2710-2712 (2003).
  • Weinstein, E., Peeva, E., Putterman, C. and Diamond, B. B – Cell Biology. Rheum. Dis. Clin. N. Am. 30:159-174 (2004).
  • Peeva, E., Venkatesh, J., Michael, D., and Diamond, B. Prolactin as a modulator of B cell function; implications for SLE. Biomed. & Pharm. 58:310-319 (2004).
  • Franchin, G., Peeva, E., and Diamond, B. Pathogenesis of SLE: implications for rational therapy. Autoimmunity and inflammatory diseases. Drug Discovery Today: Disease Mechanisms. Elsevier Ltd. 3:303-308 (2004).
  • Grimaldi, CM., Hill, L., Xu, X., Peeva, E., and Diamond, B. Hormonal modulation of B cell development and repertoire selection. Molecular Immunol. 42:811-820 (2005).
  • Davidson, A., Diamond, B., Wofsy, D., and Daikh D. Block and tackle: CTLA4Ig takes on lupus. Lupus 14:197-203 (2005).
  • Diamond, B. Guest Editor: Autoimmunity. Immunological Reviews 204:5-8 (2005)
  • Grimaldi, CM. and Diamond B. B cells. Ruddy S, Harris, Ed Jr, Sledge, CB (eds.) in Kelly’s Textbook of Rheumatology, 7th edition, WB Saunders Company, Philadelphia, 2005, pp. 153-174.
  • Jacobi, AM., and Diamond B. Balancing diversity and tolerance: lessons from SLE patients. JEM 202:341-344 (2005).
  • Grimaldi, C., Hicks, R., and Diamond, B. B cell selection and susceptibility to autoimmunity. J. Immunol. 174:1775:1781 (2005).
  • Cohen-Solal, JFG, Jeganathan, V., Grimaldi, CM., Peeva, E., and Diamond, B. Sex hormones and SLE: influencing the fate of autoreactive B cells. Current Concepts in Autoimmunity edited by A. Radbruch and P.E. Lipsky, CTMI Vol. 305:67-88 (2006).
  • Davidson, A., and Diamond, B. General features of the autoimmune diseases. The Autoimmune Diseases 4th Ed Elseiver N. Rose and I. Mackay (in press)
  • Wiesendanger, M., Stanevsky, A., Kovsky, S., and Diamond, B. Novel therapeutics for systemic lupus erythematosus Curr Opin Rheumatol. 18:227:235 (2006).
  • Diamond, B., Kowal, C., Huerta, PT., Aranow, C., Mackay, M., DeGiorgio, LA., Lee, J., Triantafyllopoulou, A., Cohen-Solal, J., and Volpe, BT. Advances in Immunology, ed Frederick Walt, Elsevier Academic Press, Elsevier Inc. Vol 89:289-320 (2006).
  • Franchin, G., and Diamond. B Pulse steroids: How much is enough? Autoimmunity Reviews Elsevier B.V. 5:111-113 (2006).
  • Kowal, C., Aranow, C., Mackay, M., Diamond, B and Volpe, BT Systemic Lupus Erythematosus: Descriptive past and mechanistic future (in press).
  • Diamond, B. Systemic lupus erythematosus and Sjogren is syndrome, 2006 Lippincott Williams & Wilkins, Current Opinion in Rheumatology 2006, 18:449-450 (2006).
  • Bodor, J., Fehervari, Z., Diamond, B. and Sakaguchi, S. Regulatory T cell mediated suppression: potential role of ICER. Journal of Leukocyte Biology 81:161-171 (2006).
  • Diamond, B. and Volpe, BT. Antibodies and brain diseases: A convergence of immunology and physiology Plos Medicine, Perspectives 3:2186-2187 (2006).
  • Diamond, B., Kowal, C., Huerta, PT., Aranow, C., Mackay, M., DeGiorgio, LA., Lee, J., Triantafyllopoulou, A., Cohen-Solal, J. and Volpe, BT. Immunity and acquired alterations in cognition and emotion: lessons from SLE. Adv. Immunol. 89;289-320 (2006).
  • Grimaldi, C., Nashi, E., Venkatesh, J. And Diamond, B. B cell hyperresponsiveness and autoimmunity: a new paradigm. Adv. Exp. Med. Biol. 596:181-190 (2007).
  • Diamond, B. and Volpe, BT. Molecular mimicry: anti-DNA antibodies bind microbial and non-nucleic acid self-antigens. In Encyclopedi of Neuroimmunology, Hddad JJ (2008) Neuroimmune interactions and mechanism. In: Binder MD, Hirokawa, N., Windhorst, U, Hirsch, Mc (eds). Encyclopedia of Neuroscience. Neuroimmunology. Springer, Heidelberg, Germany (in press).
  • Sanchez-Guerrero, J., Aranow, C., Mackay, M., Volpe, B. and Diamond, B. Neuropsychiatric systemic lupus erythematosus reconsidered. Nature Clinical Practice Rheumatol. Review 4:112-113 (2008).
  • Cohen-Solal, JFG., Jeganathan, V., Hill, L., Kawabata, D., Pinto-Rodriguez, D., Grimaldi, C. and Diamond B. Hormonal regulator of B cell function and systemic lupus erythematosus. Lupus 17:528-532 (2008).
  • Huizinga, TWJ and Diamond, B. Lupus and the central nervous system. Lupus 17:376-379 (2008).
  • Diamond, B., Huerta, PT., Mina-Osorio, P., Kowal, C. and Volpe, BT. Losing your nerves? Maybe it’s the antibodies. Nature Reviews Immunology 9:449-456 (2009).
  • Davidson, A. and Diamond, B. Systemic lupus erythematosus - B cells twist and shout Immunology and Cell Biology 87:512-513 (2009).
  • Nashi, E., Wang, Y. and Diamond, B. The role of B cells in lupus pathogenesis. Int’l J of Biochemistry & Cell Biology epub (2009) NIHMS153604
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