Relatedness and HLA-DRB1 typing may discriminate the magnitude of the genetic susceptibility to tuberculosis using a household contact model

Lucena‐Silva, Norma; Baliza, M. D.; Martins, Albert Eduardo Silva; Deghaide, Neifi Hassan Saloum; Teixeira, Kirte M.; Rodrigues, Laura C.; Ximenes, Ricardo Arraes de Alencar; Donadi, Eduardo Antônio; Albuquerque, Maria de Fátima Pessoa Militão de

doi:10.1136/jech.2008.086801

Cited by 8 publications

(5 citation statements)

References 24 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data emphasize a major role of HLA system in the regulation of the immune response against pulmonary TB. A study conducted in Recife, Northeast Brazil, also identified HLA-DRB1*04 associated with pulmonary TB [ 45 ]. A recent meta-analysis of 31 studies with 3,416 TB patients and 4,515 controls also found in the Asian population HLA-DRB1*04 associated with susceptibility to TB [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Alleles of HLA-DRB1*04 Associated with Pulmonary Tuberculosis in Amazon Brazilian Population

et al. 2016

View full text Add to dashboard Cite

Immunogenetic host factors are associated with susceptibility or protection to tuberculosis (TB). Strong associations of HLA class II genes with TB are reported. We analyzed the HLA-DRB1*04 alleles to identify subtypes associated with pulmonary TB and their interaction with risk factors such as alcohol, smoking, and gender in 316 pulmonary TB patients and 306 healthy individuals from the Brazilian Amazon. The HLA-DRB1*04 was prevalent in patients with pulmonary TB (p<0.0001; OR = 2.94; 95% CI = 2.12 to 4.08). Direct nucleotide sequencing of DRB1 exon 2 identified nine subtypes of HLA-DRB1*04. The subtype HLA-DRB1*04:11:01 (p = 0.0019; OR = 2.23; 95% CI = 1.34 to 3.70) was associated with susceptibility to pulmonary TB while DRB1*04:07:01 (p<0.0001; OR = 0.02; 95% CI = 0.001 to 0.33) to protection. Notably, the interaction between alcohol and HLA-DRB1*04:11:01 increased the risk for developing pulmonary TB (p = 0.0001; OR = 51.3; 95% CI = 6.81 to 386). Multibacillary pulmonary TB, the clinical presentation of disease transmission, was strongly associated with interaction to alcohol (p = 0.0026; OR = 11.1; 95% CI = 3.99 to 30.9), HLA-DRB1*04:11:01 (p = 0.0442; OR = 2.01; 95% CI = 1.03 to 3.93) and DRB1*04:92 (p = 0.0112; OR = 8.62; 95% CI = 1.63 to 45.5). These results show that HLA-DRB1*04 are associated with pulmonary TB. Interestingly, three subtypes, DRB1*04:07:01, DRB1*04:11:01 and DRB1*04:92 of the HLA-DRB1*04 could be potential immunogenetic markers that may help to explain mechanisms involved in disease development.

show abstract

Section: Discussionmentioning

confidence: 99%

Alleles of HLA-DRB1*04 Associated with Pulmonary Tuberculosis in Amazon Brazilian Population

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Yuliwulandari found that DRB1*1202 showed a protective effect against TB in Indonesia (Yuliwulandari et al, 2010), whereas Vejbaesya (Vejbaesya et al, 2002) reported no significant difference in DRB1 alleles between TB patients and controls in Thailand. Another report from Brazil showcased overrepresention of DRB1*04 and under-representation of DRB1*15 in TB patients (Lucena et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Association between HLA-DRB1 alleles and tuberculosis: a meta-analysis

Wang²,

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Although a number of studies have reported that human leukocyte antigen (HLA)-DRB1 alleles may be correlated with tuberculosis (TB), most were based on small samples or inconsistent and unclear results. Here, we present a meta-analysis to investigate the relationship between HLA-DRB1 alleles and TB susceptibility. We gathered relevant information from published studies on the association between HLA-DRB1 alleles and TB susceptibility through a systematic research. Data from eligible fifteen studies were included in the meta-analyses. Each dataset was statistically analyzed to evaluate the HLA-DRB1 alleles by calculating the respective odds ratios (ORs) and 95% confidence intervals (CIs). The results revealed that frequencies of two DRB1 alleles were significantly decreased in TB: DRB1*03 (P = 0.016, OR = 0.78, 95%CI = 0.67-0.95) and DRB1*07 (P = 0.017, OR = 0.81, 95%CI = 0.68-0.96). Thus, our data indicate that DRB1*03 and DRB1*07 may provide protective effects against TB susceptibility. However, well-designed studies with large sample sizes are required for better understanding of this association.

show abstract

“…In this context, our group have shown that intradomiciliary contacts with secondary tuberculosis presented a higher frequency of HLA DRB1*04 alleles (OR = 2.44; P = 0.032) with an aetiological fraction of 0.15, while intradomiciliary contacts resistant to tuberculosis presented a higher frequency of DRB1*15 alleles (OR = 0.48; P = 0.049). In this study, the presence of HLA‐DRB1 alleles shared between the primary cases and their intradomiciliary communicants was a risk factor to tuberculosis ( P = 0.028) .…”

Section: Discussionmentioning

confidence: 59%

Foxp3 Expression and Nitric Oxide Production in Peripheral Blood Mononuclear Cells of Communicants with Pulmonary Tuberculosis

Cavalcanti

Almeida²,

Almeida³

et al. 2013

Scand J Immunol

Self Cite

View full text Add to dashboard Cite

The understanding of the mechanisms involved in the immune response is of significant relevance to the control of tuberculosis (TB), especially in individuals living with patients with TB. To characterize the nitric oxide (NO) production and the Foxp3 marker expression in this population, peripheral blood mononuclear cells of intradomiciliary contacts of individuals with pulmonary tuberculosis with (CTb, susceptible) and without (STb, resistant) previous history of active infection were stimulated in vitro with Mycobacterium tuberculosis antigen (TbAg) and with the mitogen Concanavalin A for 24 and 48 h. The groups analysed did not present significant difference in the Foxp3 mRNA expression nor in the NO production. Negative correlation (P = 0.09) between NO and Foxp3 after a 48-h stimulation with TbAg was observed in the STb group. In this group, after a 24-h culture stimulated with TbAg (P = 0.03), this same correlation was observed. In comparison with the cytokines previously studied by our group (Cavalcanti et al., 2009), a positive correlation was observed between IL-10 and Foxp3 after a 48-h culture of cells from communicants susceptible to tuberculosis (STb) stimulated with TbAg (P = 0.04). Evaluating the entire population, a positive correlation was observed between the cytokine TNF-a and the Foxp3 marker in the cultures stimulated for 24 (P = 0.03) and 48 (P = 0.02) hours with TbAg. Therefore, considering the similarity in the exposure and the individual capacity of responding to the contact with M. tuberculosis, the present study contributes to the comprehension of the immune regulation in individuals living with patients with TB.

show abstract

Relatedness and HLA-DRB1 typing may discriminate the magnitude of the genetic susceptibility to tuberculosis using a household contact model

Abstract: This household contact model together with the utilisation of two genetic variables permitted the evaluation of genetic factors contributing towards tuberculosis development.

Cited by 8 publications

References 24 publications

Alleles of HLA-DRB1*04 Associated with Pulmonary Tuberculosis in Amazon Brazilian Population

Alleles of HLA-DRB1*04 Associated with Pulmonary Tuberculosis in Amazon Brazilian Population

Association between HLA-DRB1 alleles and tuberculosis: a meta-analysis

Foxp3 Expression and Nitric Oxide Production in Peripheral Blood Mononuclear Cells of Communicants with Pulmonary Tuberculosis

Contact Info

Product

Resources

About