0000000000243410
AUTHOR
Jing He
Recovery of Endogenous β-Cell Function in Nonhuman Primates After Chemical Diabetes Induction and Islet Transplantation
OBJECTIVE—To describe the ability of nonhuman primate endocrine pancreata to reestablish endogenous insulin production after chemical β-cell destruction. RESEARCH DESIGN AND METHODS—Eleven monkeys (Macaca fascicularis) were rendered diabetic with streptozotocin. Eight diabetic monkeys received intraportal porcine islet transplantation. RESULTS—Two monkeys transplanted after 75 days of type 1 diabetes showed recovery of endogenous C-peptide production a few weeks after transplantation, concomitant with graft failure. Histological analysis of the pancreas of these monkeys showed insulin-positive cells, single or in small aggregates, scattered in the pancreas and adjacent to ducts. Interesting…
Compromised central tolerance of ICA69 induces multiple organ autoimmunity
For reasons not fully understood, patients with an organ-specific autoimmune disease have increased risks of developing autoimmune responses against other organs/tissues. We identified ICA69, a known β-cell autoantigen in Type 1 diabetes, as a potential common target in multi-organ autoimmunity. NOD mice immunized with ICA69 polypeptides exhibited exacerbated inflammation not only in the islets, but also in the salivary glands. To further investigate ICA69 autoimmunity, two genetically modified mouse lines were generated to modulate thymic ICA69 expression: the heterozygous ICA69(del/wt) line and the thymic medullary epithelial cell-specific deletion Aire-ΔICA69 line. Suboptimal central neg…
Role of salivary anti-SSA/B antibodies for diagnosing primary Sjögren’s syndrome
The diagnosis of primary Sjögren’s syndrome (pSS) is complex, and the saliva test is a potential method to improve the existing diagnostic criteria. Objective: To estimate the diagnostic accuracy of salivary anti-SSA/B antibodies in primary Sjögren’s syndrome (pSS), and to analyze their correlations with clinical and laboratory profiles. Study Design: This study enrolled 100 pSS patients and 140 non-pSS controls, including 40 rheumatoid arthritis (RA) patients, 40 systemic lupus erythematosus (SLE) patients, and 60 healthy controls. Unstimulated whole saliva and stimulated parotid saliva samples were collected from the subjects. Salivary anti-SSA/B antibodies were measured using an enzyme-l…
Gene therapy for type 1 diabetes: is it ready for the clinic?
This review, in addition to updating the growing list of type 1 diabetes- relevant gene therapies, offers an outline of short-term objectives that can readily be met to move, at least, adenoviral and adeno-associated viral-based protocols into the clinic, first as a means of facilitating islet allografts as well as platforms with which to introduce immunoregulatory transgenes. A wide array of genes have been tested to restore insulin production, to drive the differentiation of insulin-producing progenitors, and to confer immunosuppression in an antigen- and tissue-restricted manner.