(Fouad kandeel, M.D., Ph.D. (AEA-Scholars

.Fouad kandeel, M.D., Ph.D

Association of Egyptian-American Scholars

Abstract

Type 1 diabetes mellitus (T1DM) is a chronic progressive autoimmune disease that affects genetically-prone individuals. Although insulin replacement can ameliorate the symptoms of the endocrine disease, it does not affect the underlying autoimmune pathophysiology. Therefore; the ultimate goal of preventing the progression of T1DM in its early stages would require interference with the autoimmune processes present.

The targeted loss of beta cells in the pancreatic islets of Langerhans, causing their mass reduction and dysfunction, is the consequence of a T-cell-dependent autoimmune attack related to the effect of Th1 cells and their secreted cytokines (e.g., IL -2, IF-); this attack is suppressed by Th2-secreted anti-inflammatory cytokines (e.g.,IL-4, IL-10). Various methods aimed specifically at halting or modulating the autoimmune attack have been attempted. The first report of immune intervention in T1DM was by David Pike, who treated two patients with intravenous cortisone in 1976, after it was demonstrated in 1974 that T1DM was associated with specific human leukocyte antigen (HLA)-risk genotypes and islet cell autoantibodies. This initial attempt was followed by numerous, mostly open and uncontrolled, smaller clinical trials with a host of immunosuppressive reagents or immunomodulation, including plasmapheresis.

 To date, preclinical studies in spontaneously diabetic rodents suggest that immunomodulation with autoantigens might alter the course of autoimmune T1DM. it is now known that autoantibodies against GAD 65, IA-2, or insulin, alone or in combination, predict disease. Gad65Ab. IA-2A, and insulin autoantibodies (IAA) demonstrate not only age-dependent, high diagnostic sensitivity and specefity for T1DM, but also significant predictive value among first-degree relatives to patients with T1DM, as well as in the general population. Islet cell autoantibody positivity is also an inclusion criterion in large intervention studies using either parenteral insulin in the diabetes prevention Trial-1 (DPT-1) or nicotinamide in the European Nicotinamide Diabetes Intervention Trial (ENDIT). Although neither study showed any effect of the treatment, both studies demonstrated the reproducibility of islet autoantibody prediction for T1DM.

Various approaches in immunomodulation and tolerance induction has been explored for T1D and will be discussed, including mixed chimerism, regulatory T cells, pregnancy related immune suppression and salmonella-based combination immunotherapy for type1 diabetes. In addition the recent exciting development from Dr. Wael Nassar’s recent trial in Egypt using cell-free microvesicles and exosomes isolated from MSC for treatment of recently diagnosed T1D patients shows great promise. Treated T1D patients exhibited improvements in HbA1c levels along with increased fasting and post-oral glucose tolerance test (OGTT) stimulated C-peptide levels. Furthermore, the treatment group exhibited significant increase in plasma levels of TGF-1 and IL-10, reflecting the immune-modulatory effect of vesicles (EVs)

 This article was published in 3alamaltanmya

sponsored by Future Builders International Academy

Led by Dr.Maha Fouad