Association of anti‐cyclic citrullinated peptide antibodies and rheumatoid factor isotypes with HLA‐DRB1 shared epitope alleles in Egyptian rheumatoid arthritis patients

Raslan, Hala M.; Attia, Hazem Ali; Ibrahim, Mona H.; Hassan, Elham A.; Salama, Iman I.; Ismail, Sherif; Abdelmotaleb, Eman; Menyawi, Manal M. El; Amr, Khalda

doi:10.1111/1756-185x.13819

Cited by 8 publications

(7 citation statements)

References 33 publications

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“…Based on these data, the hypothesis of the importance of the conserved epitope structure, which forms the third β-chain hypervariable region (positions p. [70][71][72][73][74] for RA development, was postulated: whether it contains the unfavourable variants, i.e., QKRAA, QQRAA, KKRAA, QRRAA, RRRAA, or, on the contrary, the protective structure of DERAA. Moreover, amino acid substitutions at positions 11 and 13 of DR4 are also associated with RA (alleles *04:01/*04:04/*04:05 compared to DR1 *01:01) [1,8,9]. Association of the ACPAs and the hypervariable epitope alleles indicates the role of these variants in the T-cell presentation of citrullinated proteins and the further development of autoreactivity.…”

Section: Role Of Hla Genes In Rheumatoid Arthritis Developmentmentioning

confidence: 99%

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

Mikhaylenko

Немцова

Bure

et al. 2020

IJMS

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Rheumatoid arthritis (RA) is the most common inflammatory arthropathy worldwide. Possible manifestations of RA can be represented by a wide variability of symptoms, clinical forms, and course options. This multifactorial disease is triggered by a genetic predisposition and environmental factors. Both clinical and genealogical studies have demonstrated disease case accumulation in families. Revealing the impact of candidate gene missense variants on the disease course elucidates understanding of RA molecular pathogenesis. A multivariate genomewide association study (GWAS) based analysis identified the genes and signalling pathways involved in the pathogenesis of the disease. However, these identified RA candidate gene variants only explain 30% of familial disease cases. The genetic causes for a significant proportion of familial RA have not been determined until now. Therefore, it is important to identify RA risk groups in different populations, as well as the possible prognostic value of some genetic variants for disease development, progression, and treatment. Our review has two purposes. First, to summarise the data on RA candidate genes and the increased disease risk associated with these alleles in various populations. Second, to describe how the genetic variants can be used in the selection of drugs for the treatment of RA.

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Section: Role Of Hla Genes In Rheumatoid Arthritis Developmentmentioning

confidence: 99%

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

Mikhaylenko

Немцова

Bure

et al. 2020

IJMS

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“…In summary, our findings unraveled that low miR-124a expression in peripheral blood, PBMCs, and synovial fluid could assist in the diagnosis of RA. RF is believed to be a vital diagnostic and prognostic biomarker for RA, and the anti-CCP is regarded as a RA disease-specific humoral immune response [35]. Some researchers have illustrated the functionality of elevated IgM-RF, CRP, and ESR as validated laboratory parameters for the diagnosis of RA [36].…”

Section: Discussionmentioning

confidence: 99%

“…RF is believed to be a vital diagnostic and prognostic biomarker for RA, and the anti-CCP is regarded as a RA disease-specific humoral immune response [ 35 ]. Some researchers have illustrated the functionality of elevated IgM-RF, CRP, and ESR as validated laboratory parameters for the diagnosis of RA [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

The Diagnostic Value of miR-124a Expression in Peripheral Blood and Synovial Fluid of Patients with Rheumatoid Arthritis

Wu¹,

Zhang²,

Peng³

et al. 2023

Hum Hered

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Introduction: Rheumatoid arthritis (RA), a chronic autoimmune disorder, is currently a severe health threat. Previous studies have documented the altered expression of various miRNAs in RA patients. This study determined the expression of miR-124a in RA patients and estimated its diagnostic value for RA. Methods: Total 80 RA patients were enrolled as the study subjects and 36 patients with osteoarthritis were included, with another 36 healthy people as the controls. miR-124a expression levels in peripheral blood plasma, peripheral blood mononuclear cells (PBMCs), and synovial fluid were measured using RT-qPCR, followed by Pearson correlation analysis. Additionally, the association between miR-124a and major clinical indicators was assessed, such as rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and disease activity score of 28 joints (DAS28). The diagnostic efficacy of miR-124a expression in plasma, PBMCs, and synovial fluid for RA was evaluated by the receiver operating characteristic (ROC) curve, and the difference in the area under the curve (AUC) was analyzed. Results: miR-124a was downregulated in RA patients and the expression levels of miR-124a in plasma, PBMCs, and synovial fluid showed a certain degree of positive correlation. miR-124a was inversely linked with RF, ESR, and DAS28. For the diagnosis of RA patients, the AUC of plasma miR-124a was 0.899 and the cut-off value was 0.800, with 68.75% sensitivity and 94.44% specificity; the AUC of miR-124a in PBMCs was 0.937, and the cut-off value was 0.805, with 82.50% sensitivity and 91.67% specificity; the AUC of miR-124a in plasma combined with PBMCs was 0.961, with a higher diagnostic value than independent plasma or PBMCs; the AUC of miR-124a in synovial fluid was 0.929, and the cut-off value was 0.835, with 80.00% sensitivity and 88.89% specificity. Conclusion: miR-124a expression is downregulated in plasma, PBMCs, and synovial fluid of RA patients and has a high diagnostic value for RA.

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“…This association was reported in other studies [ 14 , 34 - 37 ]. Likewise, HLA-DRB1-SE, particularly the HLA-DRB1*04:05 allele, was found to be significantly associated with RA risk in ACCP-positive patients from Egypt [ 38 ] and Saudi Arabia [ 39 ]. Moreover, strong evidence suggests that HLA-DRB1*01, *04, and *10 behave as susceptible alleles, especially for ACPA seropositivity [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

The Association of Human Leukocyte Antigen Genotyping Among Sudanese Patients With Rheumatoid Arthritis: Reference to Ethnicity

Ali,

Khalid,

Hussien

et al. 2023

Cureus

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Introduction: Human leukocyte antigens (HLA) account for up to one-half of the total genetic contribution to rheumatoid arthritis (RA) risk. The study investigated the association of HLA class II genotyping with RA susceptibility in Sudanese ethnic groups. Methods: The DRB1 and DQB1 alleles and haplotypes were determined in 122 RA patients (i.e., Gaalia = 54, Johayna = 24, Baggara = 17, Nile Nubian = 12, and others = 15) and 120 healthy controls of ethnic groups (i.e., Gaalia = 44, Johayna = 11, Baggara = 15, Nile Nubian = 9, and others = 21) using a polymerase chain reaction with sequence-specific primers method. Results: Susceptibility to RA was associated with a high frequency of DRB1*04 (P = 0.04), DRB1*10 (P = 0.04), and DQB1*03 (P = 2.2 x 10 -8 /P c = 6.6 x 10 -8 ) between study ethnic groups, while protective effects were shown with DRB1*07 (P = 0.01), DQB1*02 (P = 0.02), and DQB1*06 (P = 2.2 x 10 -6 /P c = 6.6 x 10 -6 ), with an inconsistent frequency between study ethnic groups. The HLA haplotypes that were high in frequency among RA ethnic groups and showed susceptibility associations were DRB1*03-DQB1*03, DRB1*04-DQB1*03, DRB1*08-DQB1*03, DRB1*13-DQB1*02, and DRB1*13-DQB1*03 (P = 0.00003/P c = 0.0003, P = 0.0001/P c = 0.0001, P = 0.03, P = 0.004/P c = 0.03, and P = 3.79x10 -8 /P c = 3.3x10 -9 , respectively). On the contrary, DRB1*03-DQB1*02, DRB1*07-DQB1*02, and DRB1*13-DQB1*06 were lower in frequency in the ethnic groups with RA and may confer protection (P = 0.004/P c = 0.032, P = 0.002/P c = 0.02, and P = 0.01, respectively). Conclusions: Our findings indicate an association between HLA-DRB1 and DQB1 genotypes and the susceptibility to RA in the Sudanese population, with a moderate frequency between our ethnic groups.

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Association of anti‐cyclic citrullinated peptide antibodies and rheumatoid factor isotypes with HLA‐DRB1 shared epitope alleles in Egyptian rheumatoid arthritis patients

Cited by 8 publications

References 33 publications

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

The Diagnostic Value of miR-124a Expression in Peripheral Blood and Synovial Fluid of Patients with Rheumatoid Arthritis

The Association of Human Leukocyte Antigen Genotyping Among Sudanese Patients With Rheumatoid Arthritis: Reference to Ethnicity

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