A Novel Autoantibody against β2-Glycoprotein I/HLA Class II Complexes in Antiphospholipid Syndrome

We have found that a novel autoantibody against β2-glycoprotein I (β2GPI)/human leukocyte antigen (HLA) class II complexes (anti-β2GPI/HLA-DR) is involved in the pathogenesis of antiphospholipid syndrome (APS). It was also found that many APS patients who were negative for conventional antiphospholipid antibodies (aPLs) possessed anti-β2GPI/HLA-DR. These results suggested that anti-β2GPI/HLA-DR measurements may be more sensitive for diagnosing APS than conventional aPLs tests. Recurrent pregnancy loss (RPL) is one of the clinical manifestations of APS. Therefore, a prospective, multicenter, cross-sectional study were conducted to assess whether anti-β2GPI/HLA-DR is also associated with RPL. This study of 227 couples with RPL revealed that 22.9% (52/227) of RPL women tested positive for anti-β2GPI/HLA-DR, and 24 (19.8%) of the 121 couples with unexplained RPL tested positive for anti-β2GPI/HLA-DR. Interestingly, thirty-five of the 52 (67.3%) RPL patients who were positive for anti-β2GPI/HLA-DR possessed no conventional aPLs of criteria. This novel autoantibody against β2GPI/HLA class II complexes may be a major risk factor for RPL, and it may be a promising biomarker for diagnosing APS.

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Binding of Human Thyrotropin Receptor Peptides to a Graves’ Disease-Predisposing Human Leukocyte Antigen Class II Molecule

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.85.3.6376 ◽

2000 ◽

Vol 85 (3) ◽

pp. 1176-1179 ◽

Cited By ~ 1

Author(s):

Yoshikuni Sawai ◽

Leslie J. DeGroot

Keyword(s):

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Graves Disease ◽

T Cell Repertoire ◽

Thyrotropin Receptor ◽

Cell Repertoire ◽

Peptide Epitopes ◽

Leukocyte Antigen

Abstract Abstract There are many reports that Graves’ disease (GD) is associated with certain human leukocyte antigen (HLA) molecules, in particular DR3. Here we examined the characteristics of binding of human TSH receptor (TSHR) peptides to this disease-associated HLA class II molecule. DR3 molecules bind TSHR immuonodominant peptide epitopes with intermediate affinity. On the contrary, DR3 binds nonimmunogenic peptides either with poor affinity or not at all, with one exceptional peptide that has extremely high affinity. These results suggest that susceptibility to GD associated with inheritance of a specific HLA class II gene is due to the influence of the HLA molecule-TSHR peptide complex on the T cell repertoire.

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Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis

Autoimmune Diseases ◽

10.1155/2012/569728 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Paola Cruz-Tapias ◽

Oscar M. Pérez-Fernández ◽

Adriana Rojas-Villarraga ◽

Alberto Rodríguez-Rodríguez ◽

María-Teresa Arango ◽

...

Keyword(s):

Risk Factor ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Meta Analysis ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Genetic Characteristics ◽

Latin Americans ◽

Leukocyte Antigen

The prevalence and genetic susceptibility of autoimmune diseases (ADs) may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA) class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1∗03:01 (OR: 4.04; 95%CI: 1.41–11.53) was found to be a risk factor for systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and type 1 diabetes mellitus (T1D). DRB1∗04:05 (OR: 4.64; 95%CI: 2.14–10.05) influences autoimmune hepatitis (AIH), rheumatoid arthritis (RA), and T1D; DRB1∗04:01 (OR: 3.86; 95%CI: 2.32–6.42) is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS) and T1D. DQB1∗06:02 and DRB1∗15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1∗06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.

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HLA Class II-DRB,-DQA and –DQB Genotypes in Peripheral Blood Shows Shifts During the Course of Sepsis

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences ◽

10.2478/prolas-2019-0002 ◽

2019 ◽

Vol 73 (1) ◽

pp. 10-16

Author(s):

Linda Bāra ◽

Jeļena Eglīte ◽

Pēteris Ošs ◽

Vinita Cauce ◽

Vilnis Lietuvietis ◽

...

Keyword(s):

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

University Hospital ◽

Control Group ◽

Hla Dr ◽

Group Data ◽

Threatening Condition ◽

Life Threatening ◽

Genetically Determined

Abstract Undeniably, sepsis is still a profoundly damaging and life-threatening condition for many individuals. With multiple changes in sepsis patients it is difficult to precisely classify an individual’s response in sepsis as proinflammatory or immunosuppressed. The aim of this study was to investigate genetically determined predisposition to developed sepsis by analysis of distribution of human leukocyte antigen (HLA) class II genes. Samples from patients with sepsis were collected at Pauls Stradiņš Clinical University Hospital, Latvia, in an intensive care unit between October 2016 and May 2017. The study group included 62 patients with sepsis, who were genotyped for HLA-DR; DQ using real time polymerase chain reaction – sequence specific primer (RT PCR-SSP). As a control group, data of 100 individuals were taken from the genetic bank of RSU Joint Laboratory of Clinical Immunology and Immunogenetics. The summarised results showed that the frequency of alleles DRB1*04:01 (OR = 5.54; 95% CI = 1.88–16.29); DRB1*07:01 (OR = 19.03; 95% CI = 2/37–152.82); DQA1*05:01 (OR = 14.17; 95% CI = 5.67–35.4); and DQB1*02:01 (OR = 50.00; 95% CI = 2.90–861.81) were significantly increased in patients with sepsis compared to the control group patients. The frequency of DRB1*16:01 (OR = 0.17, 95% CI = 0.04–0.59); DRB1*17:01 (OR = 0.04; 95% CI = 0.00–0.69); DQA1*01:01 (OR = 0.04; 95% CI = 0.00–0.31); DQA1*01:02 (OR = 0.03; 95% CI = 0.00–0.23); DQB1*02:02 (OR = 0.12; 95% CI = 0.03–0.42) alleles was lower in sepsis patients than in control subjects. The most frequent HLA-DRB1/DQA1/DQB1 haplotypes that was significantly increased in patients with sepsis were: DRB1*01:01/DQA1*05:01/DQB1*03:01 (OR = 12.6; 95% CI = 1.51–105.0; p < 0.003). Sepsis patients with pneumonia and alleles and DRB1 04:01; 07:01, DQB1 02:01 had the highest mortality rate. Undoubtedly, our preliminary data showed that development of sepsis can be associated with alleles and haplotypes of HLA class II genes. For more precise conclusion the research should be continued to include a larger patient group.

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Human Leukocyte Antigen (HLA) Class II Expression on Regulatory T Cells (Tregs) Isolated from Discarded Human Thymus is Induced by In Vitro Expansion Conditions

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2020.01.755 ◽

2020 ◽

Vol 39 (4) ◽

pp. S178-S179

Author(s):

E. Dijke ◽

T. Ellis ◽

I. Larsen ◽

I. Rebeyka ◽

D. Freed ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Leukocyte Antigen ◽

Human Thymus ◽

In Vitro Expansion

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Susceptible and Protective Human Leukocyte Antigen Class II Alleles and Haplotypes in Bahraini Type 2 (Non-Insulin-Dependent) Diabetes Mellitus Patients

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.1.213-217.2005 ◽

2005 ◽

Vol 12 (1) ◽

pp. 213-217 ◽

Cited By ~ 8

Author(s):

Ayesha A. Motala ◽

Marc Busson ◽

Einas M. Al-Harbi ◽

Manal A. A. Khuzam ◽

Emtiaz M. D. Al-Omari ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Leukocyte Antigen ◽

Insulin Dependent

ABSTRACT Whereas the genetic risk for type 1 diabetes is linked to human leukocyte antigen (HLA) class II genes, the HLA association in type 2 (non-insulin-dependent) diabetes is less clear. The association between HLA class II genotypes and type 2 diabetes was examined in adult Bahrainis, an Arab population with a high prevalence of type 2 diabetes. HLA-DRB1* and -DQB1* genotyping of 86 unrelated type 2 diabetes patients (age, 51.6 ± 8.2 years; mean duration of diabetes, 7.7 ± 7.1 years) who had a strong family history of diabetes (52 of 72 versus 0 of 89 for controls, P < 0.001) and 89 healthy subjects was done by PCR-sequence-specific priming. DRB1*040101 (0.1221 versus 0.0562, P = 0.019) and DRB1*070101 (0.2151 versus 0.0843, P < 0.001) were positively associated, while DRB1*110101 (0.0698 versus 0.1461, P = 0.014) and DRB1*160101 (0.0640 versus 0.1236, P = 0.038) were negatively associated with type 2 diabetes. DRB1*040101-DQB1*0302 (0.069 versus 0.0007; P = 0.004), DRB1*070101-DQB1*0201 (0.178 versus 0.0761, P = 0.007), DRB1*070101-DQB1*050101 (0.125 versus 0.0310, P = 0.002), and DRB1*150101-DQB1*060101 (0.0756 versus 0.0281, P = 0.008) were more prevalent among patients, while DRB1*160101-DQB1*050101 (0.0702 versus 0.0349, P = 0.05) was more prevalent among controls, conferring disease susceptibility or protection, respectively. In Bahrainis with type 2 diabetes, there is a significant association with select HLA class II genotypes, which were distinct from those in type 1 diabetes.

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Human Leukocyte Antigen-DR Expression is Significantly Related to an Increased Disease-Free and Disease-Specific Survival in Patients With Cervical Adenocarcinoma

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000783 ◽

2016 ◽

Vol 26 (8) ◽

pp. 1503-1509 ◽

Cited By ~ 6

Author(s):

Sanne Samuels ◽

Vivian M. Spaans ◽

Michelle Osse ◽

Lex A.W. Peters ◽

Gemma G. Kenter ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Squamous Cell ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Disease Specific Survival ◽

Leukocyte Antigen ◽

Class Ii Antigens ◽

Disease Free ◽

Disease Specific

ObjectivesHuman leukocyte antigen (HLA) class II antigens are expressed on antigen-presenting cells, that is, macrophages, dendritic cells, and B lymphocytes. Under the influence of IFN-γ, HLA class II molecules can also be expressed on T lymphocytes, epithelial and endothelial cells. In addition, HLA class II antigens can be expressed in a variety of malignancies; however, the link with prognosis and ultimately patient survival is controversial.MethodsThe pattern of HLA-DRA expression in cervical carcinoma was studied using immunohistochemistry. In total, 124 cervical carcinomas were examined, of which 60 (48.4%) were squamous cell carcinomas and 64 (51.6%) were adenocarcinomas.ResultsIn squamous cell carcinoma, HLA-DRA was expressed in 41 (68.3%) of 60 tumors, whereas in adenocarcinoma, HLA-DRA was expressed in 60 (93.8%) of 64 tumors (P< 0.001). In adenocarcinoma, HLA-DRA expression was associated with an increased disease-free survival (211.0 ± 13.0 vs 53.3 ± 30.5 months;P= 0.004) and disease-specific survival (226.45 ± 11.5 vs 75.8 ± 27.6 months;P= 0.002).ConclusionsUpregulation of HLA-DRA is significantly related to an increased disease-free and disease-specific survival in cervical adenocarcinoma. These data warrant further analysis of the functional role of HLA-DRA in these tumors.

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Autoantibodies against β2-glycoprotein I/HLA class II complexes may have the potential for improving diagnosis of antiphospholipid syndrome

Journal of Reproductive Immunology ◽

10.1016/j.jri.2016.10.104 ◽

2016 ◽

Vol 118 ◽

pp. 145-146

Author(s):

Kenji Tanimura ◽

Masashi Deguchi ◽

Yasuhiko Ebina ◽

Hisashi Arase ◽

Hideto Yamada

Keyword(s):

Antiphospholipid Syndrome ◽

Class Ii ◽

Hla Class Ii ◽

Glycoprotein I

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Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia: analytical cross-sectional study

Sao Paulo Medical Journal ◽

10.1590/1516-3180.2013.7170009 ◽

2014 ◽

Vol 133 (4) ◽

pp. 336-342 ◽

Cited By ~ 8

Author(s):

Lidyane Neves Miranda ◽

Fernanda Priscila Santos Reginaldo ◽

Daliana Maria Berenice Oliveira Souza ◽

Christiane Pienna Soares ◽

Tarsia Giabardo Alves Silva ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Th17 Cells ◽

Human Leukocyte ◽

Intraepithelial Neoplasia ◽

Cross Sectional Study ◽

Interleukin 17 ◽

Sectional Study ◽

Cross Sectional ◽

Leukocyte Antigen ◽

Human Leukocyte Antigen G

CONTEXT AND OBJECTIVE:Impaired local cell immunity seems to contribute towards the pathogenesis and progression of cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms promoting its progression remain unclear. Identification of new molecular markers for prognosis and diagnosis of early-stage CIN may aid in decreasing the numbers of CIN cases. Several novel immunoregulatory molecules have been discovered over the past few years, including the human leukocyte antigen G (HLA-G), which through interaction with its receptors exerts important tolerogenic functions. Several lines of evidence suggest that T-helper interleukin-17 (IL-17)-producing cells (Th17 cells) may play a role in antitumor immunity. However, recent reports have implicated Th17 cells and their cytokines in both pro and anti-tumorigenic processes. The aim of the study was to evaluate the roles of HLA-G and Th17 in the immunopathogenesis of CIN I.DESIGN AND SETTING:Analytical cross-sectional study with a control group using 58 cervical specimens from the files of a public university hospital providing tertiary-level care.METHODS:We examined HLA-G and IL-17 expression in the cervical microenvironment by means of immunohistochemistry, and correlated these findings with clinical and pathological features.RESULTS:There was a greater tendency towards HLA-G and IL-17 expression in specimens that showed CIN I, thus suggesting that these molecules have a contribution towards cervical progression.CONCLUSION:These findings suggest that HLA-G and IL-17 expression may be an early marker for assessing the progression of cervical lesions.

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β2-Glycoprotein I/HLA class II complexes are novel autoantigens in antiphospholipid syndrome

Blood ◽

10.1182/blood-2014-08-593624 ◽

2015 ◽

Vol 125 (18) ◽

pp. 2835-2844 ◽

Cited By ~ 34

Author(s):

Kenji Tanimura ◽

Hui Jin ◽

Tadahiro Suenaga ◽

Satoko Morikami ◽

Noriko Arase ◽

...

Keyword(s):

Antiphospholipid Syndrome ◽

Class Ii ◽

Hla Class Ii ◽

Glycoprotein I ◽

Key Points ◽

Hla Class Ii Molecules

Key Pointsβ2GPI complexed with HLA class II molecules was found to be a target for autoantibodies in APS. More than 80% of patients with APS possess autoantibodies against β2GPI/HLA class II complexes.

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