Abstract

The immune system of healthy individuals is capable of regulating autoimmunity through multiple mechanisms. In Type 1 Diabetes (T1D) we recently discovered natural IgM, although present at normal levels, is unable to perform its normal immunoregulatory function. Treating diabetic mice with IgM from healthy donors led to reversal of disease without immune depletion. To investigate the therapeutic potential of a human preparation of IgM, we administered an IgM-enriched preparation of immunoglobulin called Pentaglobin. Administration of Pentaglobin therapy reversed disease in diabetic NOD mice and boosted CD4 + Foxp3 + Tregs. Importantly, the impact of Pentaglobin on the immune system was limited to inhibiting beta cell destruction but was not immune depleting nor did it inhibit the immunization response to an irrelevant antigen. These findings indicate that inhibition of deleterious autoimmunity in T1D is possible while leaving protective immunity fully intact.

Details

Title
A human IgM enriched immunoglobulin preparation, Pentaglobin, reverses autoimmune diabetes without immune suppression in NOD mice
Author
Wilson, Christopher S. 1 ; Hoopes, Emilee M. 1 ; Falk, Alexander C. 1 ; Moore, Daniel J. 2 

 Vanderbilt University Medical Center, Department of Pediatrics, Ian Burr Division of Endocrinology and Diabetes, Nashville, USA (GRID:grid.412807.8) (ISNI:0000 0004 1936 9916) 
 Vanderbilt University Medical Center, Department of Pediatrics, Ian Burr Division of Endocrinology and Diabetes, Nashville, USA (GRID:grid.412807.8) (ISNI:0000 0004 1936 9916); Vanderbilt University Medical Center, Department of Pathology, Microbiology, and Immunology, Nashville, USA (GRID:grid.412807.8) (ISNI:0000 0004 1936 9916); Vanderbilt University Medical Center, Division of Endocrinology, Department of Pediatrics, Nashville, USA (GRID:grid.412807.8) (ISNI:0000 0004 1936 9916) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2688294377
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.