Association of Human Leukocyte Antigen (HLA) class II (DRB1 and DQB1) alleles and haplotypes with Rheumatoid Arthritis in Sudanese patients

Ali, Adil; Khalid, Khalid Eltahir; Mohammed, Shehla; Akhtar, Mohammed; Saeed, Osman Khalafalla

doi:10.3389/fimmu.2023.1178546

Cited by 6 publications

(6 citation statements)

References 46 publications

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“…There was an increase in the levels of the HLA-DRB1*04 and *10 alleles in ACPA+ RA patients, according to our previous findings [ 12 ]. This association has been detected with HLA-DRB1*04 on its own [ 23 - 25 ], in combination with HLA-DRB1*10 [ 26 ], or with HLA-DRB1*09 [ 27 , 28 ].…”

Section: Discussionsupporting

confidence: 82%

“…Several studies that looked at HLA alleles and genotypes in ACPA+ RA patients found that certain subgroups of HLA-DRB1 polymorphisms, such as HLA-DRB1*01, *04, and *10, are linked to the severity of the disease’s structural damage. These polymorphisms are also likely to influence the production of ACPA by affecting antigen presentation [ 12 - 14 ]. This is the first study to look at the link between ACPA and hematological and biochemical markers, as well as the frequencies of HLA-DRB1 risk alleles in our RA population.…”

Section: Introductionmentioning

confidence: 99%

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Association of Hematological and Biochemical Parameters and HLA-DRB1 Alleles With Anti-cyclic Citrullinated Peptide Autoantibodies in Sudanese Rheumatic Patients

Khalid

2024

Cureus

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Introduction Anti-citrullinated protein/peptide antibodies (ACPA) are crucial for the diagnosis and prognosis of rheumatoid arthritis (RA) and are associated with class II HLA-DRB1 alleles. The study’s goal was to determine how DRB1 alleles and hematological and biochemical parameters affect ACPA production in RA patients from Sudan. Methods The study analyzed the hematological and biochemical parameters and the frequency of HLA-DRB1 alleles in 120 RA patients and 100 controls. Automated analyzers, ELISA, the latex agglutination test, and the Westergren method were utilized for hematological and biochemical testing. HLA class II alleles were genotyped using polymerase chain reaction-sequence-specific primers (PCR-SSP). The student’s t-test and the chi-square ( Χ 2 ) test were employed to identify significant alterations between the examined parameters and allele frequencies. Results A total of 51.7% of 120 RA patients tested positive for ACPA (ACPA+). Among those patients, the DRB1*04 and *10 alleles were significantly more prevalent (22.2% vs. 8.9%, P = 0.048 and 23.8% vs. 8.9%, P = 0.030, respectively). RA patients had significantly higher counts of platelet count test (PLT; P = 0.011), lymphocytes (LY; P = 0.000), neutrophils (NE; P = 0.025), monocytes (MO; P = 0.000), eosinophils (EO; P = 0.000), neutrophil-to-lymphocyte ratio (NLR; P = 0.006), C-reactive protein (CRP; P = 0.000), and erythrocyte sedimentation rate (ESR; P = 0.000) than controls. Patients also showed low counts of red blood cells (RBC; P = 0.003), hemoglobin (Hb; P = 0.024), mean platelet volume (MPV; P = 0.000), and basophils (BA; P = 0.048). ACPA+ RA patients had elevated white blood cells (WBC; P = 0.046), PLT (P = 0.029), and low mean corpuscular hemoglobin concentration (MCHC; P = 0.022). The hematological and biochemical parameters of ACPA+ RA patients with the DRB1*04 or *10 alleles did not differ significantly. Conclusions We found significant differences in hematological and biochemical parameters between RA patients and controls that had nothing to do with ACPA positivity or the frequency of DRB1*04 or *10 alleles.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Association of Hematological and Biochemical Parameters and HLA-DRB1 Alleles With Anti-cyclic Citrullinated Peptide Autoantibodies in Sudanese Rheumatic Patients

Khalid

2024

Cureus

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“…As early as 1976, Stastny (44) reported a correlation between RA and the HLA-DR4 allele of the human leukocyte antigen class II. Many studies have confirmed the association between RA and HLA-DR4 in a various of different ethnic groups, but the subtypes of HLA-DR4 and other types of HLA-DR vary widely among ethnic groups (45)(46)(47)(48). Given the limited sample size and racial difference in previous studies, more large-scale research should focus on investigating the genetic contribution of HLA risk loci in IAA patients worldwide.…”

Section: Discussionmentioning

confidence: 99%

The causal relationship between immune-mediated inflammatory diseases and aortic aneurysm: A bidirectional two-sample Mendelian randomization study

Sun,

et al. 2024

Preprint

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Introduction: Many observational studies have identified aortic aneurysm (AA) as a cardiovascular complication of immune-mediated inflammatory diseases (IMIDs). However, due to the effects of various confounders, it is still uncertainty whether this association holds or whether reverse causality is involved. Here we conducted a two-sample bidirectional MR study to infer the causal relationships between the two diseases. Method: We obtained genetic association datasets from public GWAS databases in populations of European ancestry. Abiding by the assumptions of Mendelian randomization (MR), we selected valid instrumental variables from genetic variants. Different statistic methods were performed for MR analysis and sensitivity analysis, and the inverse variance weighted (IVW) method was regarded as the most efficient estimate of the causal effect in this study. Results: The IVW method found evidence that genetically predicted AA had a causal effect on rheumatoid arthritis (RA) (OR = 1.06, 95%CI = 1.01-1.12, p = 0.029), but not of RA or other IMIDs on AA. Besides, no evidence showed that AA may increase the risk of inflammatory bowel disease (IBD), Crohn’s disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE) and psoriasis (PSO). The sensitivity analysis confirmed the absence of heterogeneity or horizontal pleiotropy effect. Conclusion: In summary, our study discovered that genetically predicted AA may increase the risk of RA, while no evidence was found that patients with RA had an increased risk of AA. Furthermore, we confirmed no evidence of association between IBD, CD, UC, SLE, PSO and AA. This is in accordance with other reports that demonstrated the human leukocyte antigen molecule in inflammatory aortic aneurysm was a genetic risk loci. Our study provides directions for future research on genetic susceptibility to inflammatory aortic aneurysm.

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“…We reported the high frequency of HLA-DRB1*04 and *10 alleles in RA patients compared with healthy controls [ 17 ]. In this study, the HLA-DRB1*04 and *10 allele frequencies were remarkably high between the RA ethical groups, which is in concordance with population studies from different races [ 13 , 26 - 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, HLA-DRB1*04 and *10 alleles were statistically associated with ACPA seropositivity [ 17 ]. This association was reported in other studies [ 14 , 34 - 37 ].…”

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 Human Leukocyte Antigen (HLA) class II (DRB1 and DQB1) alleles and haplotypes with Rheumatoid Arthritis in Sudanese patients

Cited by 6 publications

References 46 publications

Association of Hematological and Biochemical Parameters and HLA-DRB1 Alleles With Anti-cyclic Citrullinated Peptide Autoantibodies in Sudanese Rheumatic Patients

Association of Hematological and Biochemical Parameters and HLA-DRB1 Alleles With Anti-cyclic Citrullinated Peptide Autoantibodies in Sudanese Rheumatic Patients

The causal relationship between immune-mediated inflammatory diseases and aortic aneurysm: A bidirectional two-sample Mendelian randomization study

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

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