<i><scp>HLA</scp>‐<scp>DRB</scp>1</i>shared epitope alleles in patients with rheumatoid arthritis: relation to autoantibodies and disease severity in a south Indian population

Mohan, Vasanth Konda; Ganesan, Nalini; Gopalakrishnan, Rajasekhar; Venkatesan, Vettriselvi

doi:10.1111/1756-185x.12948

Cited by 10 publications

(10 citation statements)

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“…Concerning CD, Goyette et al [ 45 ] found a significant association with DRB1*01, but there are no other studies correlating CD and HLA-A*29 and HLA-B*38. Differently from our findings, Konda Mohan et al [ 46 ] ] and Bizzari et al [ 47 ] indicated a protective role for HLA-DRB1*03 for RA in Indian and Arabic populations, respectively. These results may indicate that some relationships between AD and HLA background may be population-specific, which highlights the potential of spatial analyses to identify small-scale A*D clusters in populations from a similar background.…”

Section: Discussioncontrasting

confidence: 99%

Spatial analyzes of HLA data in Rio Grande do Sul, south Brazil: genetic structure and possible correlation with autoimmune diseases

et al. 2018

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BackgroundHLA genes are the most polymorphic of the human genome and have distinct allelic frequencies in populations of different geographical regions of the world, serving as genetic markers in ancestry studies. In addition, specific HLA alleles may be associated with various autoimmune and infectious diseases. The bone marrow donor registry in Brazil is the third largest in the world, and it counts with genetic typing of HLA-A, -B, and -DRB1. Since 1991 Brazil has maintained the DATASUS database, a system fed with epidemiological and health data from compulsory registration throughout the country.MethodsIn this work, we perform spatial analysis and georeferencing of HLA genetic data from more than 86,000 bone marrow donors from Rio Grande do Sul (RS) and data of hospitalization for rheumatoid arthritis, multiple sclerosis and Crohn’s disease in RS, comprising the period from 1995 to 2016 obtained through the DATASUS system. The allele frequencies were georeferenced using Empirical Bayesian Kriging; the diseases prevalence were georeferenced using Inverse Distance Weighted and cluster analysis for both allele and disease were performed using Getis-Ord Gi* method. Spearman’s test was used to test the correlation between each allele and disease.ResultsThe results indicate a HLA genetic structure compatible with the history of RS colonization, where it is possible to observe differentiation between regions that underwent different colonization processes. Spatial analyzes of autoimmune disease hospitalization data were performed revealing clusters for different regions of the state for each disease analyzed. The correlation test between allelic frequency and the occurrence of autoimmune diseases indicated a significant correlation between the HLA-B*08 allele and rheumatoid arthritis.ConclusionsGenetic mapping of populations and the spatial analyzes such as those performed in this work have great economic relevance and can be very useful in the formulation of public health campaigns and policies, contributing to the planning and adjustment of clinical actions, as well as informing and educating professionals and the population.Electronic supplementary materialThe online version of this article (10.1186/s12942-018-0154-8) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 99%

Spatial analyzes of HLA data in Rio Grande do Sul, south Brazil: genetic structure and possible correlation with autoimmune diseases

et al. 2018

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“…For example, DQB1*02 and DQB1*05 are significantly associated with a decreased risk and an increased risk of pemphigus vulgaris (PV), respectively [35]. DQB1*06 and DRB1*13 have a protective effect against rheumatoid arthritis (RA), while DRB1*01 and DRB1*04 have a detrimental effect [36,37,38]. DRB1*03 and DRB1*12 are respectively protective against or predisposing to autoimmune thyroid diseases (AITDs) [39].…”

Section: Discussionmentioning

confidence: 99%

HLA-DQB1 and HLA-DRB1 Variants Confer Susceptibility to Latent Autoimmune Diabetes in Adults: Relative Predispositional Effects among Allele Groups

Zhang

Lin

Yuan

et al. 2019

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Latent autoimmune diabetes in adults (LADA) was recently demonstrated to be the most frequent form of adult-onset autoimmune diabetes mellitus. Case–control studies have investigated the relationship between human leukocyte antigen (HLA)-DQB1 and HLA-DRB1 polymorphisms and LADA risk, but their conclusions are inconsistent. This study aimed to more precisely explore the correlation between these HLA gene variants and LADA development. Eight databases, including PubMed, Embase, and Medline, were systematically searched for relevant studies up to September 15, 2018. We performed this retrospective study using meta-analysis and relative predispositional effect (RPE) methods. The meta-analysis results indicated that DQB1*02 (odds ratio (OR) = 1.685, pc < 0.005) and DQB1*06 (OR = 0.604, pc = 0.010) have opposite effects on susceptibility to LADA, while a significant decrease in LADA risk caused by DQB1*05 (OR = 0.764, pc = 0.100) disappeared upon Bonferroni correction. The RPE method confirmed the roles of DQB1*02 (χ² = 46.475, p < 0.001) and DQB1*06 (χ² = 17.883, p < 0.001) and further suggested protective effects of DQB1*05 (χ² = 16.496, p < 0.001). Additionally, the meta-analysis results showed that DRB1*03 (OR = 2.685, pc < 0.013), DRB1*04 (OR = 1.954, pc < 0.013), and DRB1*09 (OR = 1.346, pc < 0.013) are associated with increased LADA risk, while DRB1*12 (OR = 0.600, pc < 0.013) and DRB1*13 (OR = 0.583, pc < 0.013) carriers have a decreased risk of developing LADA. Furthermore, the RPE method revealed that DRB1*03 (χ² = 98.754, p < 0.001), DRB1*04 (χ² = 94.685, p < 0.001), DRB1*09 (χ² = 40.489, p < 0.001), DRB1*01 (χ² = 12.181, p < 0.001), DRB1*07 (χ² = 10.882, p = 0.001), and DRB1*08 (χ² = 5.000, p = 0.025) play protective roles against LADA. LADA showed a close relationship with genetic polymorphisms of HLA-DQB1 and WHLA-DRB1, which could contribute to a better understanding of disease pathogenesis and the identification of predisposing loci in the diagnosis and treatment of LADA.

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“…MHC-II genes, particularly HLA (human leukocyte antigen) -DRB1 alleles (the so-called shared epitope [18,19]), constitute the strongest genetic risk factor, accounting for 50% of the genetic contribution to RA [20]. Association with HLA-DRB1 has been established in diferent populations across the world [21][22][23][24][25], especially in ACPApositive pathology, and diferent haplotypes of HLA-DRB1 associate with distinct RA severity and treatment response [26]. Single-nucleotide polymorphisms (SNPs) in other genes have also been linked to RA [16], including genes coding for molecules that regulate T cell activation, which will be discussed below.…”

Section: Aetiology Of Rheumatoid Arthritismentioning

confidence: 99%

Physiology and Pathology of Autoimmune Diseases: Role of CD4+ T cells in Rheumatoid Arthritis

Castro-Sánchez¹,

Roda-Navarro²

2017

Physiology and Pathology of Immunology

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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by synovial inlammation leading to bone erosion and to systemic manifestations in patients with long RA duration. Although the aetiology is unknown, several observations make currently clear that CD4 T cells play a key role in the pathogenesis: (1) RA associates with certain polymorphisms of HLA class II molecules, and (2) the repertoire and aging of CD4 T cells as well as the intracellular signalling mediating CD4 T cell activation are altered in RA patients. We describe herein the alterations found in CD4 T cells and the role of these cells in the development and progression of RA.

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HLA‐DRB1shared epitope alleles in patients with rheumatoid arthritis: relation to autoantibodies and disease severity in a south Indian population

Abstract: Our results indicate that HLA-DRB101, 04, 10 and 14 alleles are related with RA, while HLA-DRB103, 07, 11 and 13 protect against RA in our population. On the other hand, we failed to provide evidence for the association of the autoantibodies and DAS-28 with SE-positive RA patients.

Cited by 10 publications

References 32 publications

Spatial analyzes of HLA data in Rio Grande do Sul, south Brazil: genetic structure and possible correlation with autoimmune diseases

Spatial analyzes of HLA data in Rio Grande do Sul, south Brazil: genetic structure and possible correlation with autoimmune diseases

HLA-DQB1 and HLA-DRB1 Variants Confer Susceptibility to Latent Autoimmune Diabetes in Adults: Relative Predispositional Effects among Allele Groups

Physiology and Pathology of Autoimmune Diseases: Role of CD4+ T cells in Rheumatoid Arthritis

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