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Nerve Growth Factor and Its Receptor System in Rheumatologic Diseases and Pain Management
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Smriti K. Raychaudhuri, Siba P. Raychaudhuri
Psoriasis has long been known to occur in families. Approximately 40% of patients with psoriasis or PsA have a family history of these disorders in first-degree relatives [7]. The HLA antigens B13, B17, B39, and Cw6 occur with increased frequency in both psoriasis and PsA when compared with the general population [8]. In PsA, additional associations have been found with HLA-B27, chiefly in patients with predominant spinal disease, HLA-B38, HLA-B39, and the class II antigen HLA-DR4 [8].
Genetics, immunology, and pathogenesis
Published in M. Alan Menter, Caitriona Ryan, Psoriasis, 2017
Arthur Kavanaugh, Tristan Boyd
Although HLA-B alleles seem to confer increased risk for articular manifestations, HLA-C alleles confer greater susceptibility to cutaneous manifestations: HLA-Cw6 is associated with early-onset skin psoriasis, with a more severe and extensive presentation, but appears to have less of an association with articular symptoms.10 In addition to influencing disease phenotype, certain HLA antigens confer increased risk for disease progression (e.g., HLA-B39 alone and HLA-B27 in the presence of HLA-DR7), whereas others may reduce the risk of disease progression (e.g., HLA-B22 may be protective).11 Other genes, such as the shared epitope HLA-DRB1, when found in linkage disequilibrium with the aforementioned alleles, confer a worse radiological outcome (i.e., more erosive disease in peripheral joints) in PsA.12
Polymorphous Light Eruption, Hydroa Vacciniforme, and Actinic Prurigo
Published in Henry W. Lim, Herbert Hönigsmann, John L. M. Hawk, Photodermatology, 2007
Herbert Hönigsmann, Maria Teresa Hojyo-Tomoka
Mexican AP patients have shown a significantly increased frequency of HLA-A28 and HLA-B39 and HLA-DR4 (DRB1*0407) (92). In the Inuit people of Canada, an association with HLA-DR4 (DRB1*14) was found (93). Menagè et al. (81) suggested that the HLA type may have a causal role in patients with AP by determining the response to a particular peptide antigen, probably induced by UV radiation, to initiate the cutaneous response.
Efficacy and safety of secukinumab in Japanese patients with active ankylosing spondylitis: 24-week results from an open-label phase 3 study (MEASURE 2-J)
Published in Modern Rheumatology, 2020
Mitsumasa Kishimoto, Atsuo Taniguchi, Ayako Fujishige, Shuhei Kaneko, Sibylle Haemmerle, Brian O. Porter, Shigeto Kobayashi
Other than ethnicity, the demographics of this study population, including age, gender, and proportion of anti-TNF naïve patients, were comparable to that in global secukinumab studies in AS (MEASURE 1, 2, and 3), except for a lower frequency of HLA-B27 (46.7% vs >70%) and lighter body weight (64.7 kg vs 82.3 kg (MEASURE 2) [18–20,24,25]. In the current study, 16 patients were HLA-B27-negative, of which four had a history or concomitant skin diseases (1 psoriasis and 2 palmoplantar pustulosis at baseline and 1 history of palmoplantar pustulosis). Indeed, psoriasis can be seen in nearly 10% of AS patients [26], and Jadon et al. [27] reported that 24.4% of AS patients fulfilling modified New York Criteria for AS also met the Classification of Psoriatic Arthritis criteria. An additional clinical study of Japanese AS patients showed similar results in terms of HLA-B27 positivity (48.8%) [12], suggesting that these relatively lower rates in AS are likely related to the low HLA-B27 prevalence in the Japanese general population. Of note, a previous study has shown that HLA-B39 was positive in HLA-B27-negative AS patients [28]. Although HLA types other than B27 were not investigated in this study, it is possible that HLA-B27-negative patients in this study may have been positive for other AS-related HLA phenotypes.
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
To systemically investigate and further understand the underlying mechanism of HLA-related disorders, transgenic mice carrying HLA-A2, the most frequent HLA allele in human ethnic populations (Chen et al. 2012), were developed (Matsunaga et al. 1985). To date, this approach has been used to generate several HLA-related autoimmune disease models (Tables 1 and 2). During the creation of these mouse models, researchers aimed to achieve better recognition toward T cells and more stable expression of the HLA molecule introduced in mice. Therefore, various modifications have been implemented mostly in the construction of HLA transgenes. For example, chimeric human-mouse HLA structure has been adopted in most HLA class I (Figure 1(a)) and HLA class II (DR1, DR2, and DR4; Figure 1(b,c)) transgenic mice, aiming for better recognition toward murine T cells. To increase the expression level of HLA molecules, introduction of human beta-2 microglobulin (β2m) is critical for HLA class I (Khare et al. 1996), whereas depletion of murine endogenous MHC class II result in induction of HLA class II expression on T cells (Taneja et al. 2007). Murine β2m knockout is enough to deplete endogenous murine MHC I, while the HLA transgene itself was not affected (Khare et al. 1996). Importantly, the success of the introduced HLA expression seems to be dependent on its allotype (for example: HLA transgene was successful in both HLA-A2/β2m−/− and HLA-B39/β2m−/− mice (Racine et al. 2018) but failed in HLA-B27/β2m−/− mice (Khare et al. 1996)). DNA methyltransferase inhibitors were recently explored as an inducer of MHC class I in a mouse tumor model (Luo et al. 2018). Although this approach has not been applied in HLA transgenic mice yet, it may provide an avenue to improve HLA expression in the mouse models.