HLA class II polymorphisms in Spanish melanoma patients: homozygosity for HLA-DQA1 locus can be a potential melanoma risk factor

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 alleles predict recurrence and pattern of failure in early-stage melanoma patients

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.8503 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 8503-8503

Author(s):

Y. S. Chun ◽

Y. Wang ◽

J. E. Gershenwald ◽

M. I. Ross ◽

M. M. Johnson ◽

...

Keyword(s):

Early Stage ◽

Class Ii ◽

Hla Class Ii ◽

Tumor Thickness ◽

Hla Typing ◽

Risk Of Recurrence ◽

Increased Risk ◽

Melanoma Patients ◽

First Recurrence ◽

Hla Class Ii Alleles

8503 Background: Prior reports have suggested a link between specific HLA class II alleles, including HLA-DRB1*1101, and melanoma recurrence. We therefore investigated the relationship between HLA class II alleles and clinical outcome in a large population of patients who presented with localized melanoma. Methods: HLA class II alleles were determined by typing of genomic DNA from patients who presented with localized melanoma (AJCC stage IA-IIC). Patients found to have occult regional disease by sentinel node biopsy were excluded. Log-rank and Cox analysis of outcome versus standard prognostic factors and common HLA class II alleles (=5% of the population) was performed. Results: 1,241 patients underwent HLA typing. The median primary tumor thickness was 1.1 mm, 16% were ulcerated, and the median follow-up was 56 months. Tumor thickness, ulceration, and Clark level were independent predictors of recurrence. The HLA class II allele HLA-DRB1*1101 (11% of the population) independently predicted a higher risk of recurrence [hazard ratio (HR) 2.04, P=0.004] while HLA-DRB1*0401 (20% of the population) predicted a lower risk of recurrence (HR 0.42, P=0.004). HLA- DRB1*1101 was a particularly strong predictor of recurrence in stage I patients (HR 2.73, P<0.0001). Among patients who recurred, HLA- DRB1*1101 was an independent predictor of local-regional vs. distant recurrence (HR 2.7, P=0.007), and was more common in those whose first recurrence was isolated to the regional nodal basin, compared to those whose first recurrence was elsewhere or in multiple locations (24% HLA-DRB1*1101-positive vs. 14%, P<0.009). Conclusions: These results confirm that HLA-DRB1*1101 is a genetic marker of increased risk of melanoma recurrence, while HLA-DRB1*0401 is a marker of decreased risk of recurrence. HLA-DRB1*1101 is a particularly strong marker among the group of patients predicted clinically to be at the lowest overall risk for recurrence, and independently predicts pattern of recurrence (regional nodal failure). This information is of value in the development of surveillance strategies for melanoma patients, as well as the selection, stratification and randomization of early-stage melanoma patients for clinical trials. No significant financial relationships to disclose.

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MELOE-1 Antigen Contains Multiple HLA Class II T Cell Epitopes Recognized by Th1 CD4+ T Cells from Melanoma Patients

PLoS ONE ◽

10.1371/journal.pone.0051716 ◽

2012 ◽

Vol 7 (12) ◽

pp. e51716 ◽

Cited By ~ 9

Author(s):

Mathilde Bobinet ◽

Virginie Vignard ◽

Anne Rogel ◽

Amir Khammari ◽

Brigitte Dreno ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cd4 T Cells ◽

Class Ii ◽

Hla Class Ii ◽

T Cell Epitopes ◽

Melanoma Patients

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CTLA-4 gene polymorphism is associated with predisposition to coeliac disease

Gut ◽

10.1136/gut.43.2.187 ◽

1998 ◽

Vol 43 (2) ◽

pp. 187-189 ◽

Cited By ~ 143

Author(s):

I Djilali-Saiah ◽

J Schmitz ◽

E Harfouch-Hammoud ◽

J-F Mougenot ◽

J-F Bach ◽

...

Keyword(s):

Gene Polymorphism ◽

Coeliac Disease ◽

T Cell Activation ◽

Cell Activation ◽

Cytotoxic T Lymphocyte ◽

Class Ii ◽

Hla Class Ii ◽

Restriction Enzyme Digestion ◽

Cell Surface Molecule ◽

Hla Dqa1

Background—Susceptibility to coeliac disease is strongly associated with particular HLA class II alleles. However, non-HLA genetic factors are likely to be required for the development of the disease. Among candidate genes is the CTLA-4 (cytotoxic T lymphocyte associated) gene located on chromosome 2q33 in humans, which encodes a cell surface molecule providing a negative signal for T cell activation.Aims—To investigate CTLA-4 exon 1 polymorphism (position 49 A/G) in patients with coeliac disease.Patients—101 patients with coeliac disease and 130 healthy controls.Methods—Allele specific hybridisation and restriction enzyme digestion of polymerase chain reaction amplified genomic DNA.Results—The A allele of the CTLA-4 position 49 polymorphism was found on 82.2% of chromosomes in patients with coeliac disease compared with 65.8% in controls (p<0.0001), mostly in the homozygous form (68.3% in patients versus 47.7% in controls; odds ratio (OR) 2.36, 95% confidence interval (CI) 1.37 to 4.06, p=0.002). Four patients only had the G/G genotype compared with 21 controls (OR 0.21, CI 10.07 to 0.64, p=0.002). These differences were maintained when subjects were stratified according to the HLA class II phenotype, in particular when patients and controls were matched for the presence of the predisposing HLA DQB1*02 (DQ2) allele or HLA-DQA1*0501/DQB1*02 heterodimer.Conclusion—The CTLA-4 gene polymorphism is a non-HLA determinant that predisposes to coeliac disease. Whether it directly contributes to disease susceptibility or represents a marker for a locus in linkage disequilibrium with CTLA-4 needs further investigation.

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Human leukocyte antigen Class II alleles associated with acral lentiginous melanoma in Mexican Mestizo patients: A case-control study

Indian Journal of Dermatology Venereology and Leprology ◽

10.25259/ijdvl_627_19 ◽

2021 ◽

Vol 0 ◽

pp. 1-7

Author(s):

Rodrigo Roldan-Marin ◽

Lucia Rangel-Gamboa ◽

María E. Vega-Memije ◽

Susana Hernández-Doño ◽

Daniela Ruiz-Gómez ◽

...

Keyword(s):

Odds Ratio ◽

Small Sample Size ◽

Class Ii ◽

Hla Class Ii ◽

Small Sample ◽

Dermatology Department ◽

Acral Lentiginous Melanoma ◽

Mexican Mestizo ◽

Melanoma Patients ◽

Increased Susceptibility

Background: Melanoma is an aggressive cutaneous cancer. Acral lentiginous melanoma is a melanoma subtype arising on palms, soles, and nail-units. The incidence, prevalence and prognosis differ among populations. The link between expression of major histocompatibility complex Class II alleles and melanoma progression is known. However, available studies report variable results regarding the association of melanoma with specific HLA Class II loci. Aims: The aim of the study was to determine HLA Class II allele frequencies in acral lentiginous melanoma patients and healthy Mexican Mestizo individuals. Methods: Eighteen patients with acral lentiginous melanoma and 99 healthy controls were recruited. HLA Class II typing was performed based on the sequence-specific oligonucleotide method. Results: Three alleles were associated with increased susceptibility to develop acral lentiginous melanoma, namely: HLA-DRB1*13:01; pC = 0.02, odds ratio = 6.1, IC95% = 1.4–25.5, HLA-DQA1*01:03; pC = 0.001, odds ratio = 9.3, IC95% = 2.7–31.3 and HLA-DQB1*02:02; pC = 0.01, odds ratio = 3.7, IC95% = 1.4–10.3. Limitations: The small sample size was a major limitation, although it included all acral lentiginous melanoma patients seen at the dermatology department of Dr. Manuel Gea González General Hospital during the study period. Conclusion: HLA-DRB1*13:01, HLA-DQB1*02:02 and HLA-DQA*01:03 alleles are associated with increased susceptibility to develop acral lentiginous melanoma in Mexican Mestizo patients.

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An association between parameters of Th1 and Th2 cell-related functional activity and HLA gene polymorphism in individuals after anti-plague vaccination

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-2019-2-315-324 ◽

2019 ◽

Vol 9 (2) ◽

pp. 315-324 ◽

Cited By ~ 1

Author(s):

O. M. Kudryavtseva ◽

S. A. Bugorkova ◽

T. N. Shchukovskaya ◽

N. I. Mikshis ◽

A. Yu. Goncharova ◽

...

Keyword(s):

Immune Response ◽

Gene Polymorphism ◽

High Efficiency ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Live Attenuated Vaccine ◽

Leukocyte Antigen ◽

Immune Factor ◽

Hla Dqa1

In theRussian Federation, Y. pestis NIIEG strain-based live attenuated vaccine is used for immunization against plaque on epidemiological indications, displaying high efficiency. However, individual fluctuations in adaptive immunity after vaccination necessitate conducting a search for genes underlying variability of developing immune response. Of note, HLA (Human Leukocyte Antigen) gene polymorphism plays an important role in this process. In our study, we identified HLA class II haplotypes for HLA-DRB1, HLA-DQA1, and HLA-DQB1 in 120 residents of theterritoryofPre-Caspiannatural plague focus, who were immunized against plague. In addition, level of TNFα production correlated with detecting allelic groups HLA-DRB1*04 (р = 0.05) and DRB1*12 (р = 0.01). The data obtained show that HLA class II gene polymorphism can affect the level of cytokine secretion in response to plague immunization. Examining the genes regulating immune factor production will allow to get better insight into the mechanisms underlying immune response variations after vaccination as well as contribute to predicting immunogenicity and efficiency of developing vaccine preparations.

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Allelic Variation in HLA-DRB1 is Associated with Development of Anti-Drug Antibodies in Cancer Patients Treated with Atezolizumab that are Neutralizing in Vitro

10.1101/2021.04.29.21256008 ◽

2021 ◽

Author(s):

Christian Hammer ◽

Jane Ruppel ◽

Julie Hunkapiller ◽

Ira Mellman ◽

Valerie Quarmby

Keyword(s):

Cancer Patients ◽

Genetic Factors ◽

Allelic Variation ◽

Human Leukocyte ◽

Class Ii ◽

Biologic Agents ◽

Hla Class Ii ◽

Leukocyte Antigen ◽

Hla Dqa1

The treatment of diseases with biologic agents can result in the formation of anti-drug antibodies (ADA). The occurrence of ADA were reported for atezolizumab, an anti-PD-L1 monoclonal antibody widely used as immunotherapeutic treatment in cancer patients. Although drivers for ADA formation are unknown, a role for antigen presentation is likely, and variation in human leukocyte antigen (HLA) genes has been shown to be associated with occurrence of ADA for several biologics. Here, we performed an HLA-wide association study in 1,982 patients treated with atezolizumab across 8 clinical trials. On average, 29.8% of patients were ADA positive (N = 591, range of 13.5% - 38.4%), and 14.6% of patients were positive for ADA that were neutralizing in vitro (NAb, N = 278, range of 6.4% - 21.9%). We found statistically significant associations between HLA class II alleles and ADA status. The top-associated alleles were HLA-DRB1*01:01 for all ADA (p = 3.4*10-5, odds ratio = 1.96), and HLA-DQA1*01:01 when considering NAb only (p = 2.8 x 10-7, OR = 2.31). Both alleles occur together on a common HLA haplotype, and the ADA association was explained by the NAb subset. In conclusion, our study showed that HLA class II genotype contributes to the risk of developing ADA, and specifically NAb, in patients treated with atezolizumab, but suggests that genetic factors are not sufficient as clinically meaningful predictors.

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