title: Knocking out of CD38 accelerates development of a lupus-like disease in lpr mice.
abstract: OBJECTIVE
  CD38 participates in lymphocyte ontogeny and function and may be involved in autoimmunity. Absence of CD38 accelerates development of non-obese diabetic (NOD) mice diabetes and anti-CD38 antibodies are good markers of human disease. Little is known regarding systemic autoimmunity. Active SLE patients have higher numbers of CD38(+) T and B cells. CD38 is a candidate gene for the murine Lmb2 lupus locus. We aimed to investigate whether CD38 was involved in lupus development.
  
  
  METHODS
  We developed Cd38(-/-)-Fas(lpr)/Fas(lpr) mice and monitored them for development of a lupus-like disease through measurement of protein excretion in urine, histological assessment of the kidneys, quantification of circulating immunoglobulins and autoantibodies. We have also immunophenotyped 2- and 6-month old Cd38(-/-)-Fas(lpr)/Fas(lpr) mice.
  
  
  RESULTS
  We found that absence of CD38 accelerated disease development: female Cd38(-/-)-Fas(lpr)/Fas(lpr) mice presented severe proteinuria, GN, deposition of ICs in the renal medulla and increased amounts of circulating immunoglobulin G (IgG), although anti-dsDNA autoantibodies and RF were not significantly increased at disease onset. We have found that Cd38(-/-)-Fas(lpr)/Fas(lpr) male mice, similarly to other murine models of lupus, were able to control disease. Absence of CD38 in lpr mice altered differentiation of T cells and dendritic cells (DC).
  
  
  CONCLUSIONS
  Although the role of CD38 in tolerance is still to be elucidated, we provide evidence that it may play an active role in the control of a murine lupus-like disease.
authors.affiliation: Molecular Pathology Laboratory, Portuguese Institute for Oncology at Coimbra Francisco Gentil, EPE, Av. Bissaya Barreto, 98 - Apartado 2005, 3000-075 Coimbra, Portugal. marta.s.viegas@gmail.com
authors.forename: Marta S
authors.initials: MS
authors.lastname: Viegas
authors.forename: Teresa
authors.initials: T
authors.lastname: Silva
authors.forename: Maria M
authors.initials: MM
authors.lastname: Monteiro
authors.forename: Anália
authors.initials: A
authors.lastname: do Carmo
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Martins
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D011507:Proteinuria / Q000209:etiology; D012737:Sex Factors; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1