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Diabetes mellitus
Published in Catherine Nelson-Piercy, Handbook of Obstetric Medicine, 2020
This is an organ-specific autoimmune disease associated with serological evidence of autoimmune destruction of the pancreas and islet cell antibodies. There is a genetic component and a strong association with the human leukocyte antigens HLA-DR3 and DR4. A possible viral component to the aetiology is thought to explain the seasonal incidence (spring and autumn).
Immunology of Insulin-Dependent Diabetes Mellitus
Published in Irun R. Cohen, Perspectives on Autoimmunity, 2020
Christian Boitard, H. O. McDevitt
The development of IDDM correlates with the presence of biological markers related to immune involvement in the disease process. In addition to clinical observation of association between IDDM and other autoimmune diseases and morphological evidence of mononuclear cell infiltration of the islets of Langerhans at the onset of the disease, ICA are detected in the serum of IDDM patients. A strong genetic association with HLA-DR3 and DR4 identifies a genetic background compatible with autoimmune phenomena. Whether the autoimmune process participates to the selective destruction of insulin-secreting cells or not has been a major issue in the past 5 years. The presence of T-lymphocytes and islet cell antibodies which selectively inhibit or lyse insulin-secreting cells in vitro strongly suggests that this may be the case. Whether antiislet immune reaction appears as a primary autoimmune event or is triggered by an initial damage to the islet by environmental factors, i.e., a virus or chemicals, is still to be answered.
Gastroenterology and hepatology
Published in Shibley Rahman, Avinash Sharma, A Complete MRCP(UK) Parts 1 and 2 Written Examination Revision Guide, 2018
Shibley Rahman, Avinash Sharma
Coeliac disease is caused by sensitivity to the protein gluten. Repeated exposure leads to villous atrophy which in turn causes malabsorption. Conditions associated with coeliac disease include dermatitis herpetiformis (a vesicular, pruritic skin eruption) and autoimmune disorders (type 1 diabetes mellitus and autoimmune hepatitis). It is strongly associated with HLA-DQ2 (95% of patients) and HLA-B8 (80%) as well as HLA-DR3 and HLA-DR7.
An inflammatory triangle in Sarcoidosis: PPAR-γ, immune microenvironment, and inflammation
Published in Expert Opinion on Biological Therapy, 2021
Parnia Jabbari, Mona Sadeghalvad, Nima Rezaei
Sarcoidosis is a polygenic disorder, and several genes with different phenotypes are associated with disease development. Although further investigations are needed to determine, certain HLA-alleles have been distinguished to influence susceptibility to sarcoidosis [29]. In 2009, Grunewald J et al. showed that HLA- DRB1*03 (DR3) allele is associated with Löfgren syndrome, a type of acute sarcoidosis. In their study, 301 patients with Löfgren syndrome were included, and the significant association was found between HLA-DR3 allele and disease recovery within 2 years. However, 49% of HLA-DR3 negative patients developed a non-resolving disease [30]. In addition, HLA-DRB1*15 (DR15) and DRB1*14 (DR14) have been recognized to be associated with chronic non-resolving disease [31]. It has been mentioned that among the patients with sarcoid arthritis, HLA-B8 and HLA-B14 are more prevalent alleles and HLA-DRB1*04 is considerably rare. These patients are also carriers for HLA-DR3 allele [7].
Stiff-person syndrome: an atypical presentation and a review of the literature
Published in Hospital Practice, 2021
Benjamin C. Lin, Jaspreet Johal, Keithan Sivakumar, Alissa E. Romano, Hussam A. Yacoub
Evidence for a causative link between anti-GAD antibodies and SPS is supported by in vitro studies showing inhibition of GAD activity with transfer of antibodies prepared from SPS patients’ serum, while antibodies from patients with type-I diabetes did not have the same effect [42]. Antibodies isolated from the CSF of SPS patients reduce the release of GABA from presynaptic terminals [43]. The difference between anti-GAD antibodies found in patients with type 1 diabetes and SPS may be due to targeting different epitopes on the linearized GAD65 enzyme. In SPS, the antibodies target the N-terminal, C-terminal, and middle of the linear GAD-65 epitope. At the N-terminus, they appear to target a specific 8-amino acid epitope which is common to patients with the HLA-DR3 haplotype [44]. In addition, the unique affinity of SPS patients’ anti-GAD antibodies to the C-terminal region appears to decrease enzymatic activity via a noncompetitive mechanism. Studies in animal models demonstrated dose-dependent motor dysfunction given exposure to epitope-specific monoclonal anti-GAD antibody or IgG fraction of a patient with SPS [45,46]. Finally, GABA-enhancing agents such as benzodiazepines and baclofen are found to be helpful in the treatment of SPS.
HLA transgenic mice: application in reproducing idiosyncratic drug toxicity
Published in Drug Metabolism Reviews, 2020
Takeshi Susukida, Shigeki Aoki, Tomohiro Shirayanagi, Yushiro Yamada, Saki Kuwahara, Kousei Ito
Using HLA-DR3 (DRB1*03:01) transgenic mice, an animal model for Hashimoto's thyroiditis was established via immunization with thyroglobulin, which induces autoimmune thyroiditis (Kong et al. 1996; Flynn et al. 2002; Wan et al. 2002; Karras et al. 2005; Jacob et al. 2007). Likewise, severe thyroiditis was developed in human thyroglobulin-immunized HLA-DR3/NOD mice (Flynn et al. 2001). Both HLA-DR3 and HLA-DR3/NOD mice can serve as model systems for Graves’ hyperthyroid disease, when immunized with plasmid DNA encoding the human thyrotropin receptor (Pichurin et al. 2003; Flynn, Rao, et al. 2004) or thyroid peroxidase, with the addition of either IL-12 or GM-CSF (Flynn, Gardas, et al. 2004). Moreover, HLA-DR3/NOD mice could be developed as a novel model of autoimmune hepatitis (Yuksel et al. 2015).