title: Naturally occurring immunoglobulin M (nIgM) autoantibodies prevent autoimmune diabetes and mitigate inflammation after transplantation.
abstract: OBJECTIVE
  To investigate whether polyclonal serum naturally occurring immunoglobulin M (nIgM) therapy prevents the onset and progression of autoimmune diabetes and promotes islet allograft survival.
  
  
  BACKGROUND
  nIgM deficiency is associated with an increased tendency toward autoimmune disease development. Elevated levels of nIgM anti-leukocyte autoantibodies are associated with fewer graft rejections.
  
  
  METHODS
  Four- to five-week-old female nonobese diabetic (NOD) littermates received intraperitoneal nIgM or phosphate-buffered saline/bovine serum albumin/immunoglobulin G (100 μg followed by 50-75 μg biweekly) until 18 weeks of age. C57BL/6 recipients of 300 BALB/c or 50 C57BL/6 islet grafts received saline or nIgM.
  
  
  RESULTS
  Eighty percent control mice (n = 30) receiving saline became diabetic by 18 to 20 weeks of age. In contrast, none of 33 of nIgM-treated mice became diabetic (P < 0.0001). Discontinuing therapy resulted in hyperglycemia in only 9 of 33 mice at 22 weeks postdiscontinuation, indicating development of β-cell unresponsiveness. nIgM therapy initiated at 11 weeks of age resulted in hyperglycemia in only 20% of treated animals (n = 20) compared with 80% of controls (P < 0.0001). Treatment of mildly diabetic mice with nIgM (75 μg 3× per week) restored normoglycemia (n = 5), whereas severely diabetic mice required minimal dose islet transplant with nIgM to restore normoglycemia (n = 4). The mean survival time of BALB/c islet allografts transplanted in streptozotocin-induced diabetic C57BL/6 mice was 41.2 ± 3.3 days for nIgM-treated recipients (n = 4, fifth recipient remains normoglycemic) versus 10.2 ± 2.6 days for controls (n = 5) (P < 0.001). Also, after syngeneic transplantation, time taken to return to normoglycemia was 15.4 ± 3.6 days for nIgM-treated recipients (n = 5) and more than 35 days for controls (n = 4).
  
  
  CONCLUSIONS
  nIgM therapy demonstrates potential in preventing the onset and progression of autoimmune diabetes and in promoting islet graft survival.
authors.affiliation: Department of Surgery, Division of Transplantation, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Preeti
authors.initials: P
authors.lastname: Chhabra
authors.forename: Kailo
authors.initials: K
authors.lastname: Schlegel
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
authors.forename: Peter I
authors.initials: PI
authors.lastname: Lobo
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Brayman
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control* / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival; D007075:Immunoglobulin M / Q000276:immunology*; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D011183:Postoperative Complications / Q000276:immunology / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D007075:Immunoglobulin M