Graves’ Ophthalmopathy: the Role of Cytokines in Pathogenesis
George H. Gass, Harold M. Kaplan in 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.
HLA-DR and -DQ Serotyping
M. Kam, Jeffrey L. Bidwell in 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
Bruce S. Bochner in Adhesion Molecules in Allergic Disease, 2020
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).
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].
Monitoring immunomodulation in patients with sepsis
Published in Expert Review of Molecular Diagnostics, 2021
Evdoxia Kyriazopoulou, Evangelos J. Giamarellos-Bourboulis
Human Leukocyte Antigen-DR isotype (HLA-DR) is a Major Histocompatibility Complex (MHC) class II cell surface receptor on monocytes, macrophages, and dendritic cells. It participates in antigen presentation and it is encoded by the HLA-DRA gene. Abundance of HLA-DR on the surface of antigen-presenting cells is a sign of immune competence. In sepsis, HLA-DR downregulation is the best, so far, studied marker of sepsis-induced immunosuppression. Spleen biopsies harvested postmortem from septic patients revealed low HLA-DR expression of antigen-presenting cells [49]. Several studies have been performed on the role of HLA-DR expressed on monocytes for the detection of sepsis-induced immunosuppression (Table 3). It needs to be outscored that in some studies the expression of HLA-DR is provided as the absolute number of membrane receptors and in other studies as the percentage of monocytes expressing HLA-DR. Which is the most accurate expression of sepsis-induced immunosuppression remains to be defined. The real difference between the two measurements is that the percentage expression cannot preclude the density of the receptors on the cell membrane. A major limitation of both measurements is the requirement of flow cytometry technology.
Risk variation in celiac disease in a population from Southern Spain: evaluating the influence of the DQB1*02:02 allele frequency
Published in Scandinavian Journal of Gastroenterology, 2018
Carmen M. Cabrera, Isabel M. Méndez-López, Abelardo Caballero
Apart from CD, the HLA-DR3-DQ2 genotypes are implicated as risk factors in other autoimmune diseases, mainly in the type 1 diabetes mellitus (T1D) with the highest risk [33]. Near of 90% of individuals presenting T1D has either DR3-DQ2 or DR4-DQ8 [34]. Therefore, CD and T1D shared genetic risk. Likewise, T1D is the autoimmune-associated disease more prevalent among patients with CD, detected in approximately 4% of affecting people [33]. For this, we additionally analyzed the prevalence and risk of the HLA-DR-DQ genotypes studied regarding to the autoimmune-associated conditions in our cohort of patients. We found, that similarly to the results previously described, only those patients with CD who are heterozygous for DQ2.5/DQ2.2 or DQ2.5/DQX and homozygous for DQ2.5 present an increase in the risk of having autoimmune-associated diseases.
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