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Autoimmune Diseases and a Multidisciplinary Approach to Cancer
Published in Mehwish Iqbal, Complementary and Alternative Medicinal Approaches for Enhancing Immunity, 2023
Rheumatoid arthritis is prevalent all around the globe and is impacting the lives of all ethnic groups (Jameson, 2020; Lawrence et al., 1998). Females are affected nearly three times more often than males. The age of initiation of diseases is between the later part of the 20s and the early part of the 50s; however, it can affect people of any age. Rheumatoid arthritis is a persistent disorder involving multiple systems of the body and distinguished by chronic synovitis generally involving the joints of extremities in a symmetric manner (Gorman & Cope, 2008; Jameson, 2020). The uncontrolled synovial inflammation may give rise to bone erosions, ankylosis of the joints and destruction of cartilage (Jameson, 2020). Studies conducted on families and twins specify that rheumatoid arthritis has a genetic predisposition, and nearly 70% of patients have HLA-DR1 or HLA-DR4 alleles. The utilisation of complementary and alternative medicine by patients of rheumatoid arthritis is becoming progressively famous in the United States of America and other technologically advanced countries (Venkatesha et al., 2011) (Figure 11.2).
Dupuytren's Contracture
Published in J. Terrence Jose Jerome, Clinical Examination of the Hand, 2022
The only certainty is the existence of a genetic predisposition to the disease. The study of the patient's families shows the importance of heritability where the transmission is autosomal dominant with variable penetrance. Some studies have shown a positive association with specific classes of the human leukocyte antigen (HLA) system, namely: HLA-B12, 17 HLA-A1 and DR4, 18 HLA-DR3,19 HLA-DRB1, 15 (HLA-DR2) 20 and HLA-DRB1, 01 (HLA-DR1) [2].
HLA-DR and -DQ Serotyping
Published in M. Kam, Jeffrey L. Bidwell, Handbook of HLA TYPING TECHNIQUES, 2020
In the Indian panel HLA-DR2 and DR7 are the most frequent antigens, while the frequencies of DR1, DR3, and DR4 are reduced as compared to those of the two other Caucasoid populations shown. In the Chinese panel the most notable feature is the high frequency of DR9, which at 35.4% is ten times higher than that found in any of the other populations illustrated; DR2 is present at the same high level, and DR4 and DR7 are also frequent. HLA-DR1 and DR10 were not detected in this panel.
The small molecule antibody mimic SH7139 targets a family of HLA-DRs expressed by B-cell lymphomas and other solid cancers
Published in Journal of Drug Targeting, 2020
Rod Balhorn, Monique Cosman Balhorn, Karuppiah Balakrishnan, Robert B. Rebhun
Because the Ct, Dv and Cb ligands of SH7139 bind to three separate sites that span the entire length of HLA-DR’s peptide antigen binding cavity, SH7129 binding is likely to be affected by changes in other surface amino acid residues unique to specific HLA-DRs, many of which have no impact on Lym-1 antibody binding (Figure 5(C)). HLA-DR1 variants containing the DRB1*01:01 and DRB1*01:02 β-subunits have two amino acid substitutions (βV11L and βR30C) in Site 2 (Dv binding site) that are unique to the HLA-DR1 variants. Both residues are located in positions that could induce subtle alterations in the shape of the cavity or the hydrophobic nature of its inner surface. In addition to the Site 2 sequence differences between HLA-DR10 and HLA-DR3 (the βR71K and βA74R substitutions) mentioned earlier, HLA-DR3 variants contain a surface asparagine (βN77) located right next to Site 1 that replaces the threonine present in all other HLA-DRs. The presence of this asparagine could perturb the structure of Site 1 or alter the Ct ligand’s interaction with it. The βF13H change in the surface of Site 2 in HLA-DR4 (containing DRB1*04:07) and the βA74L Site 2 substitution in HLA-DR8 (containing DRB1*08:02) are also unique to these two HLA-DRs and both are located in positions that could easily impact SH7129 binding.
Biomedical and genetic characteristics of the Ryukyuans: demographic history, diseases and physical and physiological traits
Published in Annals of Human Biology, 2019
Kae Koganebuchi, Ryosuke Kimura
In the Okinawan centenarian study that has examined over 900 centenarians from 1976, the genetic component associated with healthy ageing and remarkable longevity has been analysed (Willcox et al. 2006b, 2017). The first study using centenarian pedigrees indicated that, compared with control families, centenarian families have more long-lived siblings (Suzuki et al. 1985). A recent large-scale centenarian study in Okinawa Prefecture indicated that female and male siblings were 2.6- and 5.4-times as likely to reach the age of 90 years, respectively (Willcox et al. 2006a). The results of those centenarian studies suggest that there are genetic factors for longevity. One such longevity-related gene is HLA. An HLA study of centenarians found that the frequency of the HLA-DR1 serotype was significantly higher in Ryukyuan centenarians than in nonagenarians, while that of the HLA-DRw9 serotype in centenarians was significantly lower (Takata et al. 1987). The results regarding the HLA-DR1 serotype were replicated in another study (Akisaka et al. 1997).
Heterologous vaccination targeting prostatic acid phosphatase (PAP) using DNA and Listeria vaccines elicits superior anti-tumor immunity dependent on CD4+ T cells elicited by DNA priming
Published in OncoImmunology, 2018
Laura E. Johnson, Dirk Brockstedt, Meredith Leong, Peter Lauer, Erin Theisen, John-Demian Sauer, Douglas G. McNeel
PAP is a prostate tumor antigen, and currently the only target of an FDA-approved cancer treatment vaccine, sipuleucel-T. Sipuleucel-T has been demonstrated to elicit broad PAP-specific immunity, characterized by both IFNγ-secreting T cells (Th1-biased) and also production of antibodies and Th2-associated cytokines, both of which have been associated with improved clinical outcome.32,33 However, given the cost and complexity of this autologous vaccine, off-the-shelf vaccine approaches are highly desirable. In particular, DNA and bacterial vector vaccines that may favor the induction of a Th1 cytolytic type immune response should theoretically elicit greater anti-tumor immunity. In this report, we evaluated two vaccine approaches, each undergoing clinical evaluation as treatments for prostate cancer, using plasmid DNA or Lm as a bacterial vector, and each encoding the prostate tumor antigen PAP. These were evaluated alone and in combination for anti-tumor efficacy in a murine tumor model expressing HLA-A2 and HLA-DR1, permitting an evaluation of the magnitude and breadth of T-cell immune response. We found that while either approach elicited antigen-specific T cells and anti-tumor responses, a greater anti-tumor response was observed using DNA and using a directional prime-boost regimen. In this model, DNA immunization favored induction of MHC class II-restricted T cells, and the induction of antigen-specific CD4+ T cells was found to be important to the improved anti-tumor immunity observed. These findings have importance for the design of future anti-tumor vaccines, and PAP-targeted vaccines in particular.