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Gene Review

CD38  -  CD38 molecule

Homo sapiens

Synonyms: 2'-phospho-ADP-ribosyl cyclase, 2'-phospho-ADP-ribosyl cyclase/2'-phospho-cyclic-ADP-ribose transferase, 2'-phospho-cyclic-ADP-ribose transferase, ADP-ribosyl cyclase 1, ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1, ...
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Disease relevance of CD38

  • Taken together, the results provide compelling evidence for a new role for CD38/ADP-ribosyl cyclase in the control of bone resorption, most likely exerted via cADPr [1].
  • Active HIV replication is associated with numerous immunologic changes, the most notable and consistent of which is an increase in CD8+ T cells expressing CD38 [2].
  • Previous studies have demonstrated that the expression of CD38 on CD8+ T cells is associated with poor prognostic outcome in infected individuals with detectable plasma viremia; however, the relationship between the expression of CD38 and the frequency of HIV-specific CD8+ T cells is unclear [2].
  • V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia [3].
  • Early proliferation of CCR5(+) CD38(+++) antigen-specific CD4(+) Th1 effector cells during primary HIV-1 infection [4].

Psychiatry related information on CD38

  • Peripheral blood clone-related cells were detected by anti-idiotypic (Id) monoclonal antibodies and found to express CD22 (92% to 95%), monotypic light and heavy chain (100%), and CD38 (45%), whereas bone marrow PC were CD22-negative [5].
  • We also examined the association of CD4, CD38, and antiretroviral therapy (ART) use with these outcomes in the subset of HIV-infected adolescents [6].
  • BACKGROUND: A priori hypothesis: vaginal and/or cervical self-stimulation will not produce perceptual responses in women with "complete" spinal cord injury (SCI) at or above the highest level of entry of the hypogastric nerves (T10-12) but will produce perceptual responses if SCI is below T-10 [7].
  • Sensory thresholds to electrical stimulation were measured at the S1, L1, T10, and T5 levels before injection, after spinal anesthesia, and after the addition of epidural anesthesia [8].

High impact information on CD38

  • Monoclonal-antibody analysis of peripheral-blood T-cell subpopulations revealed virtual elimination of the Leu-3 / helper/inducer subset, an increased percentage of the Leu-2 + suppressor/cytoxic subset, and an increased percentage of cells bearing the thymocyte-associated antigen T10 [9].
  • Here we demonstrate a novel action of 3',5'-cyclic guanosine monophosphate (cGMP) in stimulating the synthesis of cADPR from beta-NAD+ by activating its synthetic enzyme ADP-ribosyl cyclase in sea urchin eggs and egg homogenates [10].
  • These plasma cells display the high levels of CD38 found on tissue plasma cells [11].
  • The CD38 lymphocyte differentiation marker: new insight into its ectoenzymatic activity and its role as a signal transducer [12].
  • The majority of the antigen-specific cells had an activated/memory phenotype, with expression of human histocompatibility leukocyte antigen (HLA) DR, CD38, and CD45RO, downregulation of CD62 leukocyte (CD62L), and low levels of expression of CD45RA [13].

Chemical compound and disease context of CD38


Biological context of CD38


Anatomical context of CD38

  • Here, we purified resting (CD38-) human B lymphocytes from tonsils in an attempt to establish culture conditions resulting in the induction of these three GC markers [22].
  • To investigate the regulation of human plasma cell survival, plasma cells were isolated from tonsils according to high CD38 and low CD20 expression [23].
  • Both confocal microscopy and Western blotting confirmed the plasma membrane localization of the CD38 protein [1].
  • We then examined the effects of CD38 on osteoclast function [1].
  • In addition, we found that CD36low/ - cells contained most of the day-12 colony-forming units-spleen (CFU-S) but were not long-term reconstituting cells, whereas the population that expressed higher levels of CD38 contained few, but significant, day-12 CFU-S and virtually all the long-term reconstituting stem cells [24].

Associations of CD38 with chemical compounds


Physical interactions of CD38

  • The unsuitability of CD38 to perform as a receptor is obviated through close interaction with the B-cell-receptor (BCR) complex and CD19 [26].
  • MHC class II/CD38/CD9: a lipid-raft-dependent signaling complex in human monocytes [29].
  • We show that CD38+ B-CLL cells bind to murine fibroblasts transfected with the CD31 ligand [30].
  • We have examined the ability of the CD3-gamma delta epsilon and CD3-zeta signaling modules of the T cell receptor (TCR) to couple CD38 to intracellular signaling pathways [31].
  • RESULTS: A reduction of PC contamination of as much as 2 log was found in the post-selection products by a flow-cytometric technique using the monoclonal antibody CD 138 alternatively coupled with CD38 and cytoplasmatic k or l light chains in separate samples [32].
  • Raft localization and association with the CD19 complex are prerequisites for CD38-mediated signals in tonsillar B cells and in continuous lines [33].

Regulatory relationships of CD38

  • Consistent with these observations, IL8-induced migration of CD38(-) LAK cells was not observed [34].
  • CD38 is expressed on human mature monocyte-derived dendritic cells and is functionally involved in CD83 expression and IL-12 induction [35].
  • CD38 co-expression analysis also showed that a small but distinct group of cells expressing low CD38 and no external CD34 antigen could be detected [36].
  • This was tested by assessing the role(s) of CD38 after signaling with agonistic anti-CD38 monoclonal antibodies or by blocking the interactions taking place between CD38 and CD31, its counterreceptor [37].
  • Interleukin 2 (IL-2) induced a marked up-modulation and surface rearrangement of CD38 in all the patients studied [26].

Other interactions of CD38

  • The majority of cells in the large Fr RO CD34+ cell population expressed the committed stage antigens CD33, CD19, CD38, or HLA-DR and contained the majority of granulocyte-macrophage colony-forming units (CFU-GM), burst-forming units-erythroid (BFU-E), and CFU-mixed lineage (GEMM) [38].
  • Hematopoietic precursors expressing strongly the CD34 antigen (CD34(s+)) and lacking CD38 or HLA-DR expression were analyzed by using three-color immunofluorescence staining [39].
  • The other PC subpopulation, population B (67 +/- 31% of total PCs), showed the opposite pattern; the antigen CD56 was strongly positive and CD19 was constantly negative, and it showed a lower CD38 expression and higher FSC/SSC values than population A [40].
  • By contrast, clonal PCs from all MGUS patients displayed a similar antigenic profile to myelomatous PCs, with clear phenotypic differences with respect to normal PCs: lower intensity of CD38 expression and a variable reactivity for markers that were not expressed in normal PCs, such as CD28, CD117, and sIg [40].
  • In high-grade NHL (Kiel classification) the absence of CD38 or presence of CD24 on tumor cells correlated with a higher degree of disease-free survival (P values 0.009 and 0.04, respectively) [41].

Analytical, diagnostic and therapeutic context of CD38

  • In situ RT-PCR revealed intense cytoplasmic staining of osteoclasts, confirming CD38 mRNA expression [1].
  • CD38 levels were generally low in the patients examined and monoclonal antibody (mAb) ligation was inefficient in signaling [26].
  • Evaluation by flow cytometry showed that the vast majority of CD34+ CB cells coexpressed CD38, CD18, HLA-DR, and CD33 [42].
  • B cell repopulation occurred a mean of 8 months after treatment and was dependent on the formation of naive B cells, which showed an increased expression of CD38 and CD5 [43].
  • METHODS: PBMC and cervical LNMC from 12 HIV-infected patients were examined for virological and immunological parameters including chemokine receptor density, HIV plasma and cellular viral load, coreceptor usage and CD38/HLA-DR expression [44].


  1. CD38/ADP-ribosyl cyclase: A new role in the regulation of osteoclastic bone resorption. Sun, L., Adebanjo, O.A., Moonga, B.S., Corisdeo, S., Anandatheerthavarada, H.K., Biswas, G., Arakawa, T., Hakeda, Y., Koval, A., Sodam, B., Bevis, P.J., Moser, A.J., Lai, F.A., Epstein, S., Troen, B.R., Kumegawa, M., Zaidi, M. J. Cell Biol. (1999) [Pubmed]
  2. Relationship between the frequency of HIV-specific CD8+ T cells and the level of CD38+CD8+ T cells in untreated HIV-infected individuals. Chun, T.W., Justement, J.S., Sanford, C., Hallahan, C.W., Planta, M.A., Loutfy, M., Kottilil, S., Moir, S., Kovacs, C., Fauci, A.S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  3. V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Kröber, A., Seiler, T., Benner, A., Bullinger, L., Brückle, E., Lichter, P., Döhner, H., Stilgenbauer, S. Blood (2002) [Pubmed]
  4. Early proliferation of CCR5(+) CD38(+++) antigen-specific CD4(+) Th1 effector cells during primary HIV-1 infection. Zaunders, J.J., Munier, M.L., Kaufmann, D.E., Ip, S., Grey, P., Smith, D., Ramacciotti, T., Quan, D., Finlayson, R., Kaldor, J., Rosenberg, E.S., Walker, B.D., Cooper, D.A., Kelleher, A.D. Blood (2005) [Pubmed]
  5. Membrane CD22 defines circulating myeloma-related cells as mature or later B cells. Perfetti, V., Vignarelli, M.C., Bellotti, V., Glennie, M.J., Zorzoli, I., Ubbiali, P., Obici, L., Massa, M., Ippoliti, G., Ascari, E., Merlini, G. Lab. Invest. (1997) [Pubmed]
  6. Natural killer cell enumeration and function in HIV-infected and high-risk uninfected adolescents. Douglas, S.D., Durako, S.J., Tustin, N.B., Houser, J., Muenz, L., Starr, S.E., Wilson, C. AIDS Res. Hum. Retroviruses (2001) [Pubmed]
  7. 'Complete' spinal cord injury does not block perceptual responses to genital self-stimulation in women. Komisaruk, B.R., Gerdes, C.A., Whipple, B. Arch. Neurol. (1997) [Pubmed]
  8. The effect of subarachnoid lidocaine and combined subarachnoid lidocaine and epidural bupivacaine on electrical sensory thresholds. Dirkes, W.E., Rosenberg, J., Lund, C., Kehlet, H. Regional anesthesia. (1991) [Pubmed]
  9. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. Gottlieb, M.S., Schroff, R., Schanker, H.M., Weisman, J.D., Fan, P.T., Wolf, R.A., Saxon, A. N. Engl. J. Med. (1981) [Pubmed]
  10. cGMP mobilizes intracellular Ca2+ in sea urchin eggs by stimulating cyclic ADP-ribose synthesis. Galione, A., White, A., Willmott, N., Turner, M., Potter, B.V., Watson, S.P. Nature (1993) [Pubmed]
  11. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Jego, G., Palucka, A.K., Blanck, J.P., Chalouni, C., Pascual, V., Banchereau, J. Immunity (2003) [Pubmed]
  12. The CD38 lymphocyte differentiation marker: new insight into its ectoenzymatic activity and its role as a signal transducer. Shubinsky, G., Schlesinger, M. Immunity (1997) [Pubmed]
  13. Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus In vivo. Callan, M.F., Tan, L., Annels, N., Ogg, G.S., Wilson, J.D., O'Callaghan, C.A., Steven, N., McMichael, A.J., Rickinson, A.B. J. Exp. Med. (1998) [Pubmed]
  14. A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro. Yagui, K., Shimada, F., Mimura, M., Hashimoto, N., Suzuki, Y., Tokuyama, Y., Nata, K., Tohgo, A., Ikehata, F., Takasawa, S., Okamoto, H., Makino, H., Saito, Y., Kanatsuka, A. Diabetologia (1998) [Pubmed]
  15. Peripheral blood CD38 expression predicts time to progression in B-cell chronic lymphocytic leukemia after first-line therapy with high-dose chlorambucil. Morabito, F., Mangiola, M., Stelitano, C., Deaglio, S., Callea, V., Malavasi, F. Haematologica (2002) [Pubmed]
  16. Clinical relevance of the expression of the CD31 ligand for CD38 in patients with B-cell chronic lymphocytic leukemia. Ibrahim, S., Jilani, I., O'Brien, S., Rogers, A., Manshouri, T., Giles, F., Faderl, S., Thomas, D., Kantarjian, H., Keating, M., Albitar, M. Cancer (2003) [Pubmed]
  17. Transaldolase is essential for maintenance of the mitochondrial transmembrane potential and fertility of spermatozoa. Perl, A., Qian, Y., Chohan, K.R., Shirley, C.R., Amidon, W., Banerjee, S., Middleton, F.A., Conkrite, K.L., Barcza, M., Gonchoroff, N., Suarez, S.S., Banki, K. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  18. NAD glycohydrolase specifically induced by retinoic acid in human leukemic HL-60 cells. Identification of the NAD glycohydrolase as leukocyte cell surface antigen CD38. Kontani, K., Nishina, H., Ohoka, Y., Takahashi, K., Katada, T. J. Biol. Chem. (1993) [Pubmed]
  19. Transfection of the c-myc oncogene into normal Epstein-Barr virus-harboring B cells results in new phenotypic and functional features resembling those of Burkitt lymphoma cells and normal centroblasts. Cutrona, G., Ulivi, M., Fais, F., Roncella, S., Ferrarini, M. J. Exp. Med. (1995) [Pubmed]
  20. Similarities in amino acid sequences of Aplysia ADP-ribosyl cyclase and human lymphocyte antigen CD38. States, D.J., Walseth, T.F., Lee, H.C. Trends Biochem. Sci. (1992) [Pubmed]
  21. Lysis of malignant B cells from patients with B-chronic lymphocytic leukemia by autologous T cells activated with CD3 x CD19 bispecific antibodies in combination with bivalent CD28 antibodies. Bohlen, H., Hopff, T., Manzke, O., Engert, A., Kube, D., Wickramanayake, P.D., Diehl, V., Tesch, H. Blood (1993) [Pubmed]
  22. CD40 and B cell antigen receptor dual triggering of resting B lymphocytes turns on a partial germinal center phenotype. Galibert, L., Burdin, N., de Saint-Vis, B., Garrone, P., Van Kooten, C., Banchereau, J., Rousset, F. J. Exp. Med. (1996) [Pubmed]
  23. Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts. Merville, P., Déchanet, J., Desmoulière, A., Durand, I., de Bouteiller, O., Garrone, P., Banchereau, J., Liu, Y.J. J. Exp. Med. (1996) [Pubmed]
  24. Expression of murine CD38 defines a population of long-term reconstituting hematopoietic stem cells. Randall, T.D., Lund, F.E., Howard, M.C., Weissman, I.L. Blood (1996) [Pubmed]
  25. Human CD38: a glycoprotein in search of a function. Malavasi, F., Funaro, A., Roggero, S., Horenstein, A., Calosso, L., Mehta, K. Immunol. Today (1994) [Pubmed]
  26. CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells. Deaglio, S., Capobianco, A., Bergui, L., Dürig, J., Morabito, F., Dührsen, U., Malavasi, F. Blood (2003) [Pubmed]
  27. CD38 ligation results in activation of the Raf-1/mitogen-activated protein kinase and the CD3-zeta/zeta-associated protein-70 signaling pathways in Jurkat T lymphocytes. Zubiaur, M., Izquierdo, M., Terhorst, C., Malavasi, F., Sancho, J. J. Immunol. (1997) [Pubmed]
  28. Evidence for a causal role of CD38 expression in granulocytic differentiation of human HL-60 cells. Munshi, C.B., Graeff, R., Lee, H.C. J. Biol. Chem. (2002) [Pubmed]
  29. MHC class II/CD38/CD9: a lipid-raft-dependent signaling complex in human monocytes. Zilber, M.T., Setterblad, N., Vasselon, T., Doliger, C., Charron, D., Mooney, N., Gelin, C. Blood (2005) [Pubmed]
  30. CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival. Deaglio, S., Vaisitti, T., Bergui, L., Bonello, L., Horenstein, A.L., Tamagnone, L., Boumsell, L., Malavasi, F. Blood (2005) [Pubmed]
  31. The CD3-gamma delta epsilon transducing module mediates CD38-induced protein-tyrosine kinase and mitogen-activated protein kinase activation in Jurkat T cells. Zubiaur, M., Guirado, M., Terhorst, C., Malavasi, F., Sancho, J. J. Biol. Chem. (1999) [Pubmed]
  32. High-dose therapy in multiple myeloma: effect of positive selection of CD34+ peripheral blood stem cells on hematologic engraftment and clinical outcome. Patriarca, F., Damiani, D., Fanin, R., Grimaz, S., Geromin, A., Cerno, M., Sperotto, A., Silvestri, F., Zaja, F., Baccarani, M. Haematologica (2000) [Pubmed]
  33. CD38/CD19: a lipid raft-dependent signaling complex in human B cells. Deaglio, S., Vaisitti, T., Billington, R., Bergui, L., Omede', P., Genazzani, A.A., Malavasi, F. Blood (2007) [Pubmed]
  34. Activation of CD38 by interleukin-8 signaling regulates intracellular Ca2+ level and motility of lymphokine-activated killer cells. Rah, S.Y., Park, K.H., Han, M.K., Im, M.J., Kim, U.H. J. Biol. Chem. (2005) [Pubmed]
  35. CD38 is expressed on human mature monocyte-derived dendritic cells and is functionally involved in CD83 expression and IL-12 induction. Fedele, G., Frasca, L., Palazzo, R., Ferrero, E., Malavasi, F., Ausiello, C.M. Eur. J. Immunol. (2004) [Pubmed]
  36. Multiparametric analysis of immature cell populations in umbilical cord blood and bone marrow. McGuckin, C.P., Pearce, D., Forraz, N., Tooze, J.A., Watt, S.M., Pettengell, R. Eur. J. Haematol. (2003) [Pubmed]
  37. CD38 orchestrates migration, survival, and Th1 immune response of human mature dendritic cells. Frasca, L., Fedele, G., Deaglio, S., Capuano, C., Palazzo, R., Vaisitti, T., Malavasi, F., Ausiello, C.M. Blood (2006) [Pubmed]
  38. Isolation of small, primitive human hematopoietic stem cells: distribution of cell surface cytokine receptors and growth in SCID-Hu mice. Wagner, J.E., Collins, D., Fuller, S., Schain, L.R., Berson, A.E., Almici, C., Hall, M.A., Chen, K.E., Okarma, T.B., Lebkowski, J.S. Blood (1995) [Pubmed]
  39. Apoptotic regulation in primitive hematopoietic precursors. Peters, R., Leyvraz, S., Perey, L. Blood (1998) [Pubmed]
  40. Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients. Implications for the differential diagnosis between MGUS and multiple myeloma. Ocqueteau, M., Orfao, A., Almeida, J., Bladé, J., González, M., García-Sanz, R., López-Berges, C., Moro, M.J., Hernández, J., Escribano, L., Caballero, D., Rozman, M., San Miguel, J.F. Am. J. Pathol. (1998) [Pubmed]
  41. Immunophenotyping of non-Hodgkin's lymphoma. Correlation with relapse-free survival. Schuurman, H.J., Huppes, W., Verdonck, L.F., Van Baarlen, J., Van Unnik, J.A. Am. J. Pathol. (1988) [Pubmed]
  42. Phenotype analysis of hematopoietic CD34+ cell populations derived from human umbilical cord blood using flow cytometry and cDNA-polymerase chain reaction. Thoma, S.J., Lamping, C.P., Ziegler, B.L. Blood (1994) [Pubmed]
  43. Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Leandro, M.J., Cambridge, G., Ehrenstein, M.R., Edwards, J.C. Arthritis Rheum. (2006) [Pubmed]
  44. Chemokine/CD4 receptor density ratios correlate with HIV replication in lymph node and peripheral blood of HIV-infected individuals. Nokta, M.A., Li, X.D., Nichols, J., Mallen, M., Pou, A., Asmuth, D., Pollard, R.B. AIDS (2001) [Pubmed]
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