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Modulating Cytolytic Responses to Infectious Pathogens
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Rebecca Pogue Caley, Jeffrey A. Frelinger
In order to determine whether a hierarchy of preferred amino acids existed at nonanchor positions, Ruppert et al. analyzed HLA-A2-restricted peptides for binding [60]. The peptides separated into three groups: high-, intermediate-, and low-affinity binders. The amino acids in the nonanchor positions of the high-affinity binders were compared with intermediate- and low-affinity peptides. There was a strong association of certain amino acids at particular nonanchor positions in high-affinity peptides (Figure 3). This approach has also been applied to HLA-A24 and HLA-B35 [61,62].
Inflammatory bowel disease
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Giovanni Monteleone, Markus F. Neurath, Britta Siegmund
Another instructive locus that has consistently been identified by linkage and association studies as important for both ulcerative colitis and Crohn's disease in many different populations is the major histocompatibility complex (MHC) region on chromosome 6p21.1–23 (IBD3 locus). The MHC locus is highly complex, with both human leukocyte antigen (HLA) and non-HLA alleles (e.g., tumor necrosis factor and complement genes), such that, despite extensive study, the specific genes and mechanism(s) involved in conferring genetic risk remain enigmatic. In ulcerative colitis, the most consistently replicated association is with the rare allele HLA-DRB1*0103. This variant is present in 0.2%–3.2% of the population, in 6%–10% of all ulcerative colitis cases, in 15.8% of severe and extensive ulcerative colitis cases, and in 14.1%–25% of severe ulcerative colitis cases requiring colectomy. HLA-DRB1*0103 is also associated with colonic Crohn's disease. The common HLA allele HLA-DRB1*0701 is associated with Crohn's disease, and ileal Crohn's disease in particular. The alleles HLA-B27, HLA-B35, and HLA-DRB1*0103 are also associated with extraintestinal manifestations of disease. Together, these studies predict the importance of both MHC class I- and MHC class II-related immune responses and consequently CD8 and CD4 T cells in the immunopathogenesis of these disorders.
HLA and Disease Associations
Published in Soldano Ferrone, B. G. Solheim, HLA Typing: Methodology and Clinical Aspects, 2019
B. G. Solheim, L. P. Ryder, A. Svejgaard
The associations between HLA-B35 and sub-acute thyroditis, and between HLA-B5 and Behcet’s disease might be explained by preferential HLA-A, -B, -C restriction in T lymphocyte mediated lysis of virus infected cells. Thus, the HLA-B35 antigen could be particularly effective in the presentation to T effector lymphocytes of a putative thyrotropic virus which may be the cause of this disease.
Reactivation of Graves’ Disease and Thyroid Eye Disease following COVID-19 Vaccination – A Case Report
Published in Ocular Immunology and Inflammation, 2023
Chien-Wei Hung, Chih-Heng Hung
Possible pathophysiological mechanisms underlying thyroid disease and COVID-19 vaccination remained controversial.1 First, the molecular mimicry theory stated that the SARS-CoV-2 spike protein encoded by vaccines was shown to share a genetic similarity with a large heptapeptide human protein including thyroid peroxidase (TPO) peptide sequences, and the resulting antibodies might cause cross-reactivity to thyroid antigens.10 Second, autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was the consequence of dysregulation of immune system following exposure to adjuvants, such as polyethylene glycol (PEG) lipid conjugates in Pfizer-BioNTech and Moderna vaccines; and many autoimmune endocrine diseases have been reported to be related to ASIA after injection of existing vaccines such as human papillomavirus, influenza, and hepatitis B vaccines.11 Third, certain genetic predisposition of HLA might be considered for susceptibility to adverse effects on thyroid. Activation of the antigen-HLA-B*35 complex might lead to immune-mediated destruction of thyroid follicular cells.1 A meta-analysis of the association of HLA-B*46 with GD in Asian populations indicated a positive association (OR = 2.48; 95% CI: 1.93–3.13).12
Evaluation of HLA class I and HLA class II allele profile and its relationship with clinical features in patients with alopecia areata: a case–control study
Published in Journal of Dermatological Treatment, 2022
Yıldız Hayran, Melek Gunindi Korkut, Ayşe Öktem, Orhan Şen, Güneş Gür Aksoy, Füsun Özmen
AA is an autoimmune skin disease which precipitating factors such as stress or infections may trigger the disease in genetically susceptible patients. Positive family history in patients with AA and increased frequency of the disease in monozygotic twines suggest a genetic background of AA (22–24). Studies investigating genetic risk factors of the diseases identified many susceptibility loci including HLA. HLA-A*02, HLA-A*03, HLA-B*18, HLA-B*27, HLA-B*52, HLA-C*07, and HLA-DQB1*06 were identified as a risk factor in Chinese Han population, HLA-DQB1*03 in Italian population, HLA-C*04 and HLA-C*15 in Japanese population (16–20). In Turkish population, HLA-A*01, HLA-B*62, HLA-DQB1*01, and HLA-DQB1*03 were more frequent compared to healthy controls (25–27). Our results showed increased frequencies of HLA-B*39 and HLA-DRB1*15 alleles in patients with AA compared to healthy controls. On the other hand, the presence of HLA-A*11 and HLA-B*35 alleles were associated with decreased disease risk in our study. Similar to our results Aliagaoglu et al. also showed a protective effect of HLA-B*35 allele in Turkish patients (25). HLA-A*02, HLA-A*24, HLA-DQB1*06, HLA-DRB1*11, and HLA-DRB1*15 are other HLA alleles with decreased frequency in AA patients compared to the control group (17,20,25).
HLA and amyotrophic lateral sclerosis: a systematic review and meta-analysis
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2023
R. J. Nona, J. M. Greer, R. D. Henderson, P. A. McCombe
Our meta-analyses found two statistically significant genotypic frequency HLA associations with ALS; however, after correction for multiple comparisons, these would no longer be significant. The frequency of the HLA-A9 serotype was lower in ALS subjects, and all eight studies showed a similar pattern. The frequency of the HLA-B35 serotype was higher in ALS subjects than in controls. Of the seven individual studies that reported results for HLA-B35, six showed that pattern; however, the result was strongly influenced by the two of the studies (23,24). The HLA-DR4 serotype showed a reduced frequency in ALS compared to controls, but this based on only one study (28). Our meta-analysis did not confirm the previously reported associations of ALS with HLA-A3, HLA-B7, and HLA-B16.