KIR/HLA Combination Associated with the Risk of Complications in Celiac Disease

2011 ◽  
Vol 26 (4) ◽  
pp. 221-228 ◽  
Author(s):  
Laura Caggiari ◽  
Giuseppe Toffoli ◽  
Valli De Re ◽  
Nicoletta Orzes ◽  
Michele Spina ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Blood Donors ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Gluten Free ◽  
Predisposing Factor ◽  
Leukocyte Antigen ◽  
Hla Genes ◽  
Clinical Complications ◽  
Hla Ligands

The pathogenesis of celiac disease (CD) is associated with polymorphisms in human leukocyte antigen (HLA) genes; however, compelling evidence suggests that additional non-HLA genes are associated with CD and related complications. The present study investigated whether killer cell immunoglobulin-like receptor (KIR)/HLA gene combinations are associated with CD and its clinical complications in the population of northeast Italy. The study included 61 adults affected by CD: 48 patients were at first diagnosis and 13 patients had CD-related complications (8 with refractory CD and 5 with cancer). Controls were 69 blood donors genotyped for KIR and HLA. Several statistically significant differences emerged between CD patients and blood donors. The results herein presented show that susceptibility to CD with refractory disease or cancer is associated with various genotypes including the 2DS2/2DL2+C1, 2DS3, 3DL1, and 2DL5B genes. In addition, the absence of the Bw4 ligand may be a predisposing factor for cancer. These results suggest that a KIR haplotype and HLA ligands may be involved in the susceptibility to important clinical CD complications such as tumors or refractoriness as a result of a gluten-free diet.

scholarly journals Celiac Disease Revisited

2021 ◽  
pp. 1-14
Author(s):  
João Calado ◽  
Mariana Verdelho Machado
Keyword(s):  
Celiac Disease ◽  
Systemic Disease ◽  
Human Leukocyte ◽  
Risk Groups ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Serological Tests ◽  
Leukocyte Antigen ◽  
Human Leukocyte Antigen Haplotype ◽  
Circulating Autoantibodies

Celiac disease (CD) is a systemic disease triggered by gluten ingestion in genetically predisposed individuals. It manifests primarily as an autoimmune enteropathy associated with specific circulating autoantibodies and a human leukocyte antigen haplotype (HLA-DQ2 or HLA-DQ8). It afflicts roughly 1% of the population, though the majority of patients remain undiagnosed. Diarrhea and malabsorption are classic manifestations of CD; however, both children and adults can be paucisymptomatic and present extraintestinal manifestations such as anemia, osteoporosis, and abnormal liver tests. CD screening is not recommended for the general population, and it should be focused on high-risk groups. CD diagnosis is challenging and relies on serological tests, duodenal histology, and genetic testing. Particularly difficult presentations to manage are seronegative patients, seropositive patients without villus atrophy, and patients who have started a gluten-free diet before the diagnostic workup. The only proven treatment is a lifelong gluten-free diet. We present an in-depth review on the physiopathology and management of CD, with a particular emphasis on diagnostic challenges.

Immunogenetics of Celiac Disease: A Focus on Arab Countries

2020 ◽  
Vol 20 (4) ◽  
pp. 275-285 ◽  
Author(s):  
Nadin Younes ◽  
Salma Younes ◽  
Ola. A. Alsharabasi ◽  
Mohamed E. El Zowalaty ◽  
Ibrahim Mustafa ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Genetic Epidemiology ◽  
Arab World ◽  
Human Leukocyte ◽  
Epidemiological Studies ◽  
Arab Countries ◽  
Global Perspective ◽  
Genetic Profile ◽  
Leukocyte Antigen ◽  
Genetic And Environmental Factors

Celiac Disease (CD) is a complex immunogenic disease mainly triggered by gluten intake in genetically susceptible individuals with a prevalence of 1 in 100-300. CD results from the interplay between genetic and environmental factors. Genetic susceptibility is believed to play a prominent role in the pathogenicity of CD, mainly due to human leukocyte antigen (HLA)-related class II genes. Although CD is wellrecognized among Arab populations, there are few studies on the genetic epidemiology and prevalence of CD in the Arab countries. Therefore, the aim of this review was to highlight the importance of studying this disease in the Arab world in the context of a global perspective. Within the few studies published so far, it was found that Arab populations have a distinctive susceptibility genetic profile from other ethnic groups with the DQ2.5 and DQ8 genotypes that are considered the major genotypes that confer susceptibility among Arab patients with CD. Our findings will pave the way to perform further epidemiological studies that will help identify potential therapeutic targets against CD among Arab patients that are diagnosed with CD.

scholarly journals Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elham Ashouri ◽  
Karan Rajalingam ◽  
Shaghik Barani ◽  
Shirin Farjadian ◽  
Abbas Ghaderi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Cancer ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Risk Scores ◽  
Hla Ligands ◽  
Nk Cytotoxicity

AbstractHuman leukocyte antigen (HLA) class I-specific killer-cell immunoglobulin-like receptors (KIR) regulate natural killer (NK) cell function in eliminating malignancy. Breast cancer (BC) patients exhibit reduced NK-cytotoxicity in peripheral blood. To test the hypothesis that certain KIR-HLA combinations impairing NK-cytotoxicity predispose to BC risk, we analyzed KIR and HLA polymorphisms in 162 women with BC and 278 controls. KIR-Bx genotypes increased significantly in BC than controls (83.3% vs. 71.9%, OR 1.95), and the increase was more pronounced in advanced-cancer (OR 5.3). No difference was observed with inhibitory KIR (iKIR) and HLA-ligand combinations. The activating KIR (aKIR) and HLA-ligand combinations, 2DS1 + C2 (OR 2.98) and 3DS1 + Bw4 (OR 2.6), were significantly increased in advanced-BC. All patients with advanced-cancer carrying 2DS1 + C2 or 3DS1 + Bw4 also have their iKIR counterparts 2DL1 and 3DL1, respectively. Contrarily, the 2DL1 + C2 and 3DL1 + Bw4 pairs without their aKIR counterparts are significantly higher in controls. These data suggest that NK cells expressing iKIR to the cognate HLA-ligands in the absence of putative aKIR counterpart are instrumental in antitumor response. These data provide a new framework for improving the utility of genetic risk scores for individualized surveillance.

scholarly journals Structural plasticity of KIR2DL2 and KIR2DL3 enables altered docking geometries atop HLA-C

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shoeib Moradi ◽  
Sanda Stankovic ◽  
Geraldine M. O’Connor ◽  
Phillip Pymm ◽  
Bruce J. MacLachlan ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Human Leukocyte Antigen ◽  
Nk Cells ◽  
Natural Killer ◽  
Crystal Structures ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Functional Differences ◽  
Molecular Bases

AbstractThe closely related inhibitory killer-cell immunoglobulin-like receptors (KIR), KIR2DL2 and KIR2DL3, regulate the activation of natural killer cells (NK) by interacting with the human leukocyte antigen-C1 (HLA-C1) group of molecules. KIR2DL2, KIR2DL3 and HLA-C1 are highly polymorphic, with this variation being associated with differences in the onset and progression of some human diseases. However, the molecular bases underlying these associations remain unresolved. Here, we determined the crystal structures of KIR2DL2 and KIR2DL3 in complex with HLA-C*07:02 presenting a self-epitope. KIR2DL2 differed from KIR2DL3 in docking modality over HLA-C*07:02 that correlates with variabilty of recognition of HLA-C1 allotypes. Mutagenesis assays indicated differences in the mechanism of HLA-C1 allotype recognition by KIR2DL2 and KIR2DL3. Similarly, HLA-C1 allotypes differed markedly in their capacity to inhibit activation of primary NK cells. These functional differences derive, in part, from KIR2DS2 suggesting KIR2DL2 and KIR2DL3 binding geometries combine with other factors to distinguish HLA-C1 functional recognition.

scholarly journals The molecular basis of how buried human leukocyte antigen polymorphism modulates natural killer cell function

2020 ◽  
Vol 117 (21) ◽  
pp. 11636-11647 ◽  
Author(s):  
Philippa M. Saunders ◽  
Bruce J. MacLachlan ◽  
Phillip Pymm ◽  
Patricia T. Illing ◽  
Yuanchen Deng ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Peptide Binding ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Cell Recognition ◽  
Leukocyte Antigen ◽  
Binding Cleft

Micropolymorphisms within human leukocyte antigen (HLA) class I molecules can change the architecture of the peptide-binding cleft, leading to differences in peptide presentation and T cell recognition. The impact of such HLA variation on natural killer (NK) cell recognition remains unclear. Given the differential association of HLA-B*57:01 and HLA-B*57:03 with the control of HIV, recognition of these HLA-B57 allomorphs by the killer cell immunoglobulin-like receptor (KIR) 3DL1 was compared. Despite differing by only two polymorphic residues, both buried within the peptide-binding cleft, HLA-B*57:01 more potently inhibited NK cell activation. Direct-binding studies showed KIR3DL1 to preferentially recognize HLA-B*57:01, particularly when presenting peptides with positively charged position (P)Ω-2 residues. In HLA-B*57:01, charged PΩ-2 residues were oriented toward the peptide-binding cleft and away from KIR3DL1. In HLA-B*57:03, the charged PΩ-2 residues protruded out from the cleft and directly impacted KIR3DL1 engagement. Accordingly, KIR3DL1 recognition of HLA class I ligands is modulated by both the peptide sequence and conformation, as determined by the HLA polymorphic framework, providing a rationale for understanding differences in clinical associations.

Erratum to: Killer-cell immunoglobulin-like receptor and human leukocyte antigen-C genes in common variable immunodeficiency

2015 ◽  
Vol 128 (7-8) ◽  
pp. 305-305
Author(s):  
Ozgur Kartal ◽  
Ugur Musabak ◽  
Sait Yesillik ◽  
Rahsan I. Sagkan ◽  
Aysel Pekel ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Common Variable Immunodeficiency ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Common Variable

Sa1325 The Human Leukocyte Antigen DQ 2.2 and Celiac Disease

2012 ◽  
Vol 142 (5) ◽  
pp. S-273 ◽  
Author(s):  
Amani Mubarak ◽  
Eric Spierings ◽  
Victorien M. Wolters ◽  
Ingrid M. van Hoogstraten ◽  
Corneille M. Kneepkens ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Leukocyte Antigen
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