P-230 Poster of distinction

The role of polyclonal serum immunoglobulin M (IgM) therapy in preventing the onset of autoimmune type 1 diabetes as well as the recurrence of the disease in islet transplantation

P. Chhabra¹, F. Mukheef¹, L. Langman¹, K. Schlegel², P. Lobo², K. Brayman  ^1
1 University of Virginia, Surgery, Transplant Division, Charlottesville, USA; ² University of Virginia, Medicine, Nephrology Division, Charlottesville, USA

Objective: The object of this study is to investigate the role of purified polyclonal serum immunoglobulin M (IgM) therapy in preventing the onset of autoimmune type 1 diabetes (T1D) as well as the recurrence of the disease following islet transplantation.

Methods: Mouse polyclonal IgM was purified from serum using Sephacryl S-300 HR column chromatography (yield 0.1mg/ml sera). 8 weeks old NOD litter-mates were distributed into two groups: saline-injected control mice (n=20) and IgM-injected test mice (n=13). Test mice received purified serum IgM (100ug/100ul PBS; intraperitoneal) initially, followed by 50ug/100ul biweekly maintenance dose. Control mice were injected in parallel with 100uls saline.

Results: Preliminary results indicate that while none of the mice in the IgM-treated test group became diabetic, 80% of the control mice became diabetic over the same time period (t-test p<0.001). Discontinuing IgM treatment in the test group resulted in the appearance of T1D in only three mice at 3 months time-point (experiment still in progress). Examination of aldedhyde fuchsin-stained pancreas sections indicates severe insulitis as well as severe periductal and perivascular inflammation in islets from the control diabetic mice. In contrast, normal appearance or mild early stage insulitis is observed in the IgM-treated mice islets accompanied by some periductular and perivascular inflammation. When compared to controls, incubation of human islets in the presence of 2-8ug human IgM in vitro, did not affect insulin secretion in response to glucose challenge as determined by glucose stimulated insulin secretion assay.

Conclusions: Preliminary studies indicate that purified polyclonal serum IgM therapy has tremendous therapeutic potential in the prevention of the onset of autoimmune T1D and may prove a beneficial intervention in preventing recurrence of the disease following islet transplantation.

P-230 Poster of distinction

The role of polyclonal serum immunoglobulin M (IgM) therapy in preventing the onset of autoimmune type 1 diabetes as well as the recurrence of the disease in islet transplantation

P. Chhabra¹, F. Mukheef¹, L. Langman¹, K. Schlegel², P. Lobo², K. Brayman  ^1
1 University of Virginia, Surgery, Transplant Division, Charlottesville, USA; ² University of Virginia, Medicine, Nephrology Division, Charlottesville, USA

Objective: The object of this study is to investigate the role of purified polyclonal serum immunoglobulin M (IgM) therapy in preventing the onset of autoimmune type 1 diabetes (T1D) as well as the recurrence of the disease following islet transplantation.

Methods: Mouse polyclonal IgM was purified from serum using Sephacryl S-300 HR column chromatography (yield 0.1mg/ml sera). 8 weeks old NOD litter-mates were distributed into two groups: saline-injected control mice (n=20) and IgM-injected test mice (n=13). Test mice received purified serum IgM (100ug/100ul PBS; intraperitoneal) initially, followed by 50ug/100ul biweekly maintenance dose. Control mice were injected in parallel with 100uls saline.

Results: Preliminary results indicate that while none of the mice in the IgM-treated test group became diabetic, 80% of the control mice became diabetic over the same time period (t-test p<0.001). Discontinuing IgM treatment in the test group resulted in the appearance of T1D in only three mice at 3 months time-point (experiment still in progress). Examination of aldedhyde fuchsin-stained pancreas sections indicates severe insulitis as well as severe periductal and perivascular inflammation in islets from the control diabetic mice. In contrast, normal appearance or mild early stage insulitis is observed in the IgM-treated mice islets accompanied by some periductular and perivascular inflammation. When compared to controls, incubation of human islets in the presence of 2-8ug human IgM in vitro, did not affect insulin secretion in response to glucose challenge as determined by glucose stimulated insulin secretion assay.

Conclusions: Preliminary studies indicate that purified polyclonal serum IgM therapy has tremendous therapeutic potential in the prevention of the onset of autoimmune T1D and may prove a beneficial intervention in preventing recurrence of the disease following islet transplantation.