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HLA-DR and -DQ Serotyping
Published in M. Kam, Jeffrey L. Bidwell, Handbook of HLA TYPING TECHNIQUES, 2020
HLA-DR-DQ Associations in Different Populations. Table 7 shows the most frequent DR-DQ associations found in different ethnic groups. The main associations shown are those found in British Caucasoids,35 representing a northern European population; different associations found in other major ethnic groups are indicated in parentheses. Some conclusions are HLA-DR1 is associated with DQ5(1) and DR103 is found with either DQ5(1) or DQ7(3).HLA-DR15 is DQ6(1) associated and DR16 is found with DQ5(1). In South American Indians DR16 has been found with DQ7(3).51HLA-DR17(3) is found together with DQ2 in all ethnic groups, and DR18(3) associated with DQ4 is found in Black African populations.44In northern Europe DR4 is found with either DQ7(3) or DQ8(3). In Asian populations a proportion of DR4s are associated with DQ4. Recently DR4-DQ2 was reported as a haplotype in the Sudan52 and Greece.53HLA-DR11 is associated with DQ7(3) in all population groups and in Black populations DR11-DQ6Q) is also found.54 HLA-DR12 is usually found with DQ7(3) in European populations, while in Zimbabwean Shona it is more frequently found with DQ6(1).55In European populations HLA-DR13 is usually associated with DQ6(1), but it has been found with DQ2, DQ5(1), and DQ7(3) in American Blacks.56 HLA-DR1403, described in Asians, is DQ7(3) associated45 and DR14-DQ7(3) is also found in South American Indians;51 other DR14s, including DR1404, are usually found with DQ5(1).HLA-DR7 can be found with either DQ2 or more infrequently with DQ9(3).The DQ association of DR8 varies very markedly in different population groups; in Europeans DR8 is found most often with DQ4, in Asians DR8 occurs most commonly with DQ(1),57 and in African populations, such as Nigerians, DR8 occurs with DQ7(3).58HLA-DR9 is found with DQ9(3) in Europeans and Asians and with DQ2 in Black populations.54HLA-DR10 is found with DQ5(1) in all populations.
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
In the IHC assays conducted in this study, SH7129 exhibited very strong binding to its target as evidenced by its detection on the surface of the PBMCs expressing certain HLA-DRs even after thirteen buffer washes and two incubations (Table 2 and Figures 2 and 4). These results are consistent with the affinity of SH7129 reported previously for HLA-DR10 expressing Raji lymphoma cells (Kd ∼ 23pM) [22]. Although SH7129 is only 1/60th the size of an antibody, its affinity for HLA-DR7, HLA-DR9, HLA-DR10, HLA-DR11, HLA-DR12, HLA-DR13, HLA-DR15 and HLA-DR16 is similar to the best therapeutic monoclonal antibodies, which typically bind to their antigens with nM to pM affinities [97]. The observed lack of staining of PBMCs expressing HLA-DR1, HLA-DR3, HLA-DR4, HLA-DR8 and HLA-DR14 is most likely due to sequence differences predominantly in Site 2 that prevent Dv binding and to changes in Site 3 that block Cb binding. SH7129 may still bind to these HLA-DRs, but its affinity may not be high enough to remain bound under the stringent washing conditions used in our IHC assay. A one thousand-fold reduction in SHAL affinity would be expected if the sequence or structural changes eliminated the ability of one ligand to bind to HLA-DR. Bidentate SHALs containing only two ligands typically bind to their target protein with affinities in the nanomolar range. Picomolar affinities have only been observed with tridentate SHALs containing three ligands or with bis-bidentate SHALs that bind bivalently to two neighbouring HLA-DRs [22].
A case of Löfgren’s syndrome evaluated by imaging modalities: musculoskeletal ultrasound, MRI and PET-CT
Published in Modern Rheumatology Case Reports, 2020
Tomohisa Uchida, Keita Fujikawa, Akira Kondo, Akinari Mizokami, Kazuhiro Kurohama, Masahiro Nakashima, Atsushi Kawakami, Katsumi Eguchi
We describe a patient with Löfgren’s syndrome evaluated by MSUS, MRI and PET-CT. To the best of our knowledge, this is the first report that describes the articular manifestations using various imaging modalities. Löfgren’s syndrome is characterised by the triad of acute arthritis, hilar lymphadenopathy and erythema nodosum [2]. The most frequently affected joint is ankle [7]. While the incidence of this syndrome is thought to vary among geographic regions and ethnic backgrounds, the syndrome is very rare in Japan [8,9]. Only 12 cases have been reported to date in Japan [9]. The variability in the incidence rates may be associated with HLA haplotypes. Several studies have found an association between HLA-DRB1*03 and Löfgren’s syndrome [10–12]. This HLA haplotype is very rare (0.1%) in the general population of Japan, and no reports have described Japanese patients with HLA-DRB1*03 [9,13,14]. Moreover, the possibility of an association between HLA-DR12 and the pathogenesis of Löfgren’s syndrome was suggested in a literature review involving Japanese patients [9]. To confirm the association between HLA haplotype and Löfgren’s syndrome in Japanese patients, the accumulation of cases is necessary. The prognosis of Löfgren’s syndrome is favourable, and spontaneous regression is typically observed for 2 weeks to 4 months [15]. Although the condition typically responds to treatment with non-steroidal anti-inflammatory drugs, a short course of corticosteroids (initial doses of prednisolone: 15–40 mg daily) may be required in severe cases [7].
Lichen sclerosus of the vulva
Published in Climacteric, 2021
Studies that support genetic susceptibility in the pathogenesis of the condition indicate a significant association of LSV with genes regulating human leukocyte antigen (HLA) class II antigens, which are involved in humoral immunity. Women with LSV have an increased prevalence of HLA-DQ7, HLA-DQ8, HLA-DQ9 and HLA-DR12 compared with controls, with 50% of adult females expressing HLA-DQ7. In contrast, HLA-DR17 shows a negative association with LSV, inferring protective qualities. These specific HLA antigens and their associated haplotypes may play a role in susceptibility and protection from lichen sclerosus [11,12].