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HLA-DR and -DQ Serotyping
Published in M. Kam, Jeffrey L. Bidwell, Handbook of HLA TYPING TECHNIQUES, 2020
The key to improving HLA-DR and -DQ typing by serology is in obtaining more specific reagents. In the future the use of monoclonal antibodies, especially those of human origin, may become more important, although for some variants it is unlikely that monospecific reagents will be found because of the degree of sequence and epitope sharing with other alleles.5 IHWs provide the channel through which the exchange of reagents between laboratories worldwide facilitates the identification and ratification of new specificities. Newly identified HLA-DR specificities are generally recognized as patterns of "extras" or "misses" in sera with other reactivity. For example, the authors are able to identify a "short" DR4 pattern (a DR4 that is negative with certain DR4-positive sera and monoclonal antibodies) that corresponds to the DR4-Dw10 (DRB1*0402) variant.53 The development of HLA class II serology has always been aided by the alternative means of identifying HLA-DR and -DQ variants, i.e., by HLA-Dw typing and more recently by restriction fragment length polymorphism (RFLP) typing, oligonucleotide typing, and DNA sequencing. As individuals with a new HLA-DR or -DQ type are recognized, it becomes possible to screen for reagents, possibly those that are monospecific, to define that specificity.
Eosinophil–Epithelial Interactions and Transepithelial Migration
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
Mary K. Schroth, James M. Stark, Julie B. Sedgwick, William W. Busse
Mast cells reside within the lung epithelium and interstitial tissues and contain an important profile of preformed mediators. The mast cell is activated by cross-linking of its high-affinity IgE receptors (FcsRI) through allergen-specific binding (19); activation may also occur through non-IgE dependent events, e.g., osmotic factors, opiates, and other stimuli (20). Following activation, mast cells release preformed mediators, including histamine and tryptase, and begin to synthesize cytokines such as TNF-α (20,20a). Histamine is a potent vasodilator and airway smooth muscle contractor. Significantly increased levels of histamine are found in BAL fluid of subjects with allergic asthma and following antigen exposure (21). Histamine can stimulate airway epithelial cells to produce IL-6 (22), IL-8 (22), fibronectin (23), and GM-CSF (22,24), and enhance expression of ICAM-1 and human leukocyte, D related (HLA-DR) on cultured bronchial cells from asthmatic subjects (25). The increased expression of ICAM-1 on bronchial epithelial cells can further facilitate leukocyte recruitment (16). HLA-DR expression likely signifies epithelial cell activation and may serve to participate in antigen presentation (26).
Graves’ Ophthalmopathy: the Role of Cytokines in Pathogenesis
Published in George H. Gass, Harold M. Kaplan, Handbook of Endocrinology, 2020
The human leukocyte antigen termed DR (HLA-DR) is expressed on cells that are capable of presenting antigens to CD4+ lymphocytes. HLA-DR is normally present on activated T cells, monocytes, B cells, macrophages, and endothelial cells. In the setting of an autoimmune disorder, HLA-DR can be expressed on other cells that do not generally express this antigen, such as thyrocytes.33,34 In frozen biopsy specimens of orbital tissues from patients with severe GO, marked HLA-DR immunoreactivity can be detected in orbital fibroblasts including those forming the endomysial connective tissue that separates and surrounds the extraocular muscle fibers.35 No HLA-DR reactivity is apparent on the extraocular muscle cells themselves or in orbital connective tissue obtained from normal individuals. Cultured orbital, pretibial, and abdominal fibroblasts from patients with Graves’ disease or normal individuals do not express HLA-DR spontaneously. However, as is the case with many cell types, treatment in vitro of fibroblasts with IFN-γ results in induction of HLA-DR expression.17 Of particular significance is that HLA-DR expression induced by IFN-γ in orbital and pretibial fibroblasts from patients with GO and pretibial dermopathy is greater in magnitude than that expressed in abdominal fibroblasts from the same patients. These results suggest that orbital and pretibial fibroblasts may be particularly susceptible to involvement in the autoimmune process.
The value of postoperative HLA-DR expression and high mobility group box 1 level in predictive diagnosis of sepsis in percutaneous nephrolithotomy surgery
Published in Renal Failure, 2022
Hai Feng Hou, Ying Liu, Xiaoyang Zhang, Zhenhua Han, Tianming Chen
HLA-DR is a class II antigen, which is a glycosylated transmembrane protein expressed on antigen presenting cells. HLA-DR is also constitutively expressed on monocytes such as macrophages, dendritic cells and B cells. The expression of HLA-DR on monocytes is essential for presenting the ingested microbial peptides to CD4 or CD8 positive T cells, thus initiating specific immune responses to eliminate potential pathogens. Now, the decreased expression of monocyto HLA-DR (mHLA-DR) is considered as a reliable marker of immunosuppression and/or septic complications in critically ill patients [18]. The expression of HLA-DR can be evaluated by standardized tests in clinical practice [19]. Importantly, low levels of mHLA-DR were observed in patients with subsequent nosocomial infections [20]. On the contrary, the level of mHLA-DR returned to normal rapidly (generally within less than 1 week) in the injured patients who recovered smoothly. Reduced mHLA-DRhas thus been shown to predict adverse outcomes invarious groups of critically ill patients [21]. Compared with the normal level, patients with mHLA-DR expression less than 30% had lower survival rate and a 30-fold increased risk of death [22].
CIITA expression is regulated by histone deacetylase enzymes and has a role in α-synuclein pre-formed fibril-induced antigen presentation in murine microglial cell line
Published in Immunopharmacology and Immunotoxicology, 2022
Caner Günaydın, Z. Betül Çelik, S. Sırrı Bilge
Following the demonstration that α-synuclein increases in peripheral mononuclear cells of Parkinson's patients, and the significant increase in the number of CD4, CD8 T-lymphocytes in serum samples taken from patients, researches conducted within the framework of the autoimmune hypothesis have increased [18]. Later, a genome-wide association study performed by Nalls et al. in 2011 showed that HLA-DR or HLA-DQ expression and increased MHC-II may be risk factors for PD [19]. It has been shown that peripheral T lymphocytes and central microglia play different roles in the anti and pro-inflammatory response by differentiating the central and peripheral T lymphocyte response with increased MHC expression [20]. It has been shown in previous studies that microglial cells cause the release of iNOS, NF-κB, and pro-inflammatory cytokines and chemokines by directly internalizing α-synuclein in aggregated and fibril form increasing MHC-II expression [21]. It was also stated in these studies that the murine BV-2 cell line can be used to investigate the immune activation against pathogenic factors such as LPS or α-synuclein [22]. For this reason, we chose to investigate the effect of fibrillar form of α-synuclein in our study.
Circulating Leukocyte Alterations and the Development/Progression of Diabetic Retinopathy in Type 1 Diabetic Patients - A Pilot Study
Published in Current Eye Research, 2020
Gideon Obasanmi, Noemi Lois, David Armstrong, Nuala-Jane Lavery, Jose Romero Hombrebueno, Aisling Lynch, David M. Wright, Mei Chen, Heping Xu
The reduction in HLA-DR+ leukocyte proportions may be central to the key changes in lymphocyte populations observed in this study and may contribute to DR pathology via diminished antigen presentation and consequently, diminished ability to resist diseases.26,27 HLA-DR is a major histocompatibility complex, class II (MHC-II) molecule primarily expressed on antigen presenting cells (APCs) including dendritic cells and monocytes and is an important player in many autoimmune diseases.26,27 It primarily functions to present peptide antigens by APCs to the T-cell receptor (TCR) of T-helper cell to elicit responses that eventually lead to antibody production and T-helper cell activation and proliferation. Reduced HLA-DR in DR patients suggests a reduced capacity of APCs to present antigens, hence less T-cell activation and proliferation, and B-cell maturation.