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Other Sexually Transmitted Diseases of the Vulva and the Vagina
Published in William J. Ledger, Steven S. Witkin, Vulvovaginal Infections, 2017
William J. Ledger, Steven S. Witkin
Genital ulcers also result from infection by Klebsiella granulomatis, a Gram-negative encapsulated bacterium and the causative agent of donovanosis (granuloma inguinale). Like chancroid, donovanosis is most prevalent in warm climates. However, the two diseases differ in that the lesions of donovanosis are usually painless, but do bleed easily upon touch. Three types of donovanosis can be observed that differ in their appearance: ulcerogranulomatous (most common), hypertrophic, and sclerotic. Although donovanosis is considered a sexually transmitted infection, there is also evidence for its occurrence in children with no evidence of sexual abuse and in chaste adults.18 Mother-to-neonate infection during vaginal delivery has also been reported.19 In women, the ulcers of donovanosis are most commonly present on the labia minora, fourchette, and cervix and must be differentiated from lesions due to syphilis, chancroid, HPV, and herpesvirus. Immune-related studies on donovanosis are minimal. There is a report associating the infection to the presence of HLA B57.20
An Overview of Psoriasis
Published in John Y. M. Koo, Ethan C. Levin, Argentina Leon, Jashin J. Wu, Alice B. Gottlieb, Moderate to Severe Psoriasis, 2014
Let us now consider recent research relating to the genetics of psoriasis. It has been known for years that there is a significant association between HLA and psoriasis, specifically, class I antigens HLA-B57, B13, Cw6, and Cw7, with HLA-Cw6 appearing to confer the highest risk. The first susceptibility locus at the distal end of chromosome 17 was described in 1994 in Science [9]. This came about as a result of research at the National Psoriasis Tissue Bank based in Dallas, TX, at Baylor University Medical Center and sponsored by the National Psoriasis Foundation. In 1997, the Michigan-Kiel Group confirmed this susceptibility locus [10]. In this study of 224 sib-pairs, Nair and colleagues found linkages in the HLA region as well as additional loci on chromosome 16q and chromosome 20p. Of interest was the overlap in the 16q region with a previously described locus for Crohn’s disease; psoriasis appears more commonly in patients with Crohn’s disease. Furthermore, an Italian group has shown a locus in chromosome 1, that is, 1q21 [11]. Bowcock (the co-discoverer, with the author, of the original 17q locus) and Bhalerao in 1999 also confirmed this Italian finding [12]. Recently, after 18 years of research on this locus, the relationship between this 17q locus, CARD14, and NF-κ has been confirmed [13].
Abacavir
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Paul U. Cameron, Jason A. Trubiano
Studies of the immunologic mechanism underlying the AHR showed CD8+ T-cell-mediated recognition of abacavir or its metabolite carbovir (Martin et al., 2004a). In vitro, blood mononuclear cells from subjects with B*5701 who were exposed to abacavir showed endogenous HSP70 redistribution and activation of antigen-processing cells, but there was increased interferon-gamma production only where there was prior sensitization in an AHR (Martin et al., 2007). Recent studies suggest that abacavir-naive T-cells are capable of producing polyclonal responses to abacavir stimulation in HLA-B57*01-positive patients (Chessman et al., 2008; Lucas et al., 2015). In vivo skin biopsy after patch tests showed CD8+ T-cell infiltration (Phillips et al., 2002). Together with the risk associated with high CD8+ T-cell numbers and the class I association, this suggested a class I-restricted CD8 mechanism for disease pathogenesis. Others have suggested a role for TH0 or TH2 cytokines such as interleukin 4 (King et al., 2005). What is known is that abacavir binds noncovalently to the floor of the peptide binding groove of HLA-B*5701. The initial binding and ensuing AHR does not require drug metabolism. The change in the peptide binding groove that follows causes an alteration in the repertoire of self-peptides that bind and are presented, hence self-peptides previously not presented during thymic development and T-cell tolerance/anergy are able to induce T-cell responses from a collection that were not previously tolerated to self (Ostrov et al., 2012; Illing et al., 2012; Norcross et al., 2012; Pavlos et al., 2012).
Genetic markers of drug hypersensitivity in pediatrics: current state and promise
Published in Expert Review of Clinical Pharmacology, 2022
Abdelbaset A. Elzagallaai, Michael J. Rieder
Recent data from research on abacavir hypersensitivity have revealed another possible model of DHRs pathophysiology. Abacavir can bind to a specific HLA molecule (HLA-B*57:01) and alter the presented self-peptide repertoire leading to T-cell activation [66–68]. Activated drug-antigen self-peptide reactive CD8+ T-cells then expand releasing distinct sets of cytokines and chemokines recruiting and activating specific immune cell types to cause the DHRs manifestation. The factors are involved in the selection of the specific pathway and why some drugs (e.g. beta-lactams) can cause all types and severities of DHRs are not clear. Finally, these hypotheses are not mutually exclusive, and they may contribute subsequently or independently in the cascade of events leading to the reaction manifestations.
Inflammatory bowel disease manifestations in spondyloarthritis: considerations for the clinician
Published in Expert Review of Clinical Immunology, 2021
Ennio Lubrano, Michele Maria Luchetti, Devis Benfaremo, Daniele Mauro, Francesco Ciccia, Fabio Massimo Perrotta
A pathogenetic link shared between IBD and SpA is demonstrated by the solid clinical association between intestinal inflammation and joint inflammation. The presence of a shared genetic susceptibility further supports the idea of shared pathogenesis. Genes such as HLA-B27, NOD2/CARD15, and IL-23 R are implicated in predisposing to gut and joint inflammation in both IBD and SpA [25–27]. The association of SpA with HLA-B*27 was first described more than 40 years ago. SpA is associated with multiple HLA-B alleles that could even determine the phenotype [28]. HLA‑B*27, HLA ‑B*13: 02, HLA‑B*40:01, HLA‑B*40:02, HLA‑B*47:01, and HLA‑B*51:01 are alleles associated with an increased risk of developing AS, while the HLA-B*07:02 and HLA-B*57:01 alleles are protective. When considering the association between HLA-B27 and IBD, about 50–75% of patients with spondylitis associated with IBD have HLA-B27, and HLA-B27 appears to convey a high risk of developing axial inflammation in CD [29]. However, although many theories have been postulated to explain how HLA-B*27 is involved in the pathogenesis of SpA, none have a conclusive answer to this question, and no successful HLA-B27 targeting treatments have yet been developed.
A comprehensive overview on the genetics of Behçet's disease
Published in International Reviews of Immunology, 2022
Mahdi Mahmoudi, Saeed Aslani, Akira Meguro, Maryam Akhtari, Yousef Fatahi, Nobuhisa Mizuki, Farhad Shahram
Accumulative data identified an association of other variants in the major histocompatibility complex (MHC) region with BD risk. Among those, HLA-A*26, HLAB*15, HLA-B*27, and HLA-B*57 have been identified as the genetic risk alleles for BD. Nonetheless, there has been protective MHC class I variants for BD like HLA-A*03 and HLA-B*49 [66]. It has been demonstrated that the simultaneous inheritance of HLA-B*49 and HLA-A*03 protective alleles may reduce the pathogenic impression of the HLA-B*51 risk allele [64].