Investigação de tuberculose latente utilizando os ensaios de produção de interferon-gama (IGRA) e da proteína de 10kDa induzida por interferon (IP-10/CXCL-10) em pacientes com doença renal crônica

Abstract

There is increasing evidence that patients with chronic kidney disease (CKD) or on routine dialysis are at high risk of acquiring latent tuberculous infection (LTBI) or developing active TB. However, diagnosing LTBI remains a challenge based on current tests that reflect the cellular immune response against Mycobacterium tuberculosis infection – which may be compromised in this population. It is known that cellular immunity, represented mainly by T lymphocytes capable of producing high concentrations of interferon-gamma (IFN-γ), constitutes the main defense mechanism against Mtb. Particularly, patients with chronic kidney disease in more advanced stages of the disease present significant changes in the innate and adaptive immune response due to the accumulation of toxins, which are normally excreted by the kidneys, which makes them more vulnerable to infections by different pathogens.A prospective cross-sectional study was conducted in a tertiary nephrology reference hospital, Rio de Janeiro, Brazil. LTBI was diagnosed using interferon-gamma release assay (IGRA; QuantiFERON-TB Gold Plus [QFT-Plus]). CXCL-10/IP-10 release assay determined from QFT-Plus supernatants was also used to identify Mtb-specific immune response. Sociodemographic, clinical, and laboratorial data were obtained from medical reports and analyzed for LTBI predictors. A total of 123 patients were enrolled in the study, 111 (90.2%) from the CKD group and 12 (9,8%) from the hemodialysis (HD) group. IGRA showed 39 (31.7%) positive results in the general study population: 36/111 (32.4%) in CKD and 3/12 (25%) in HD groups. Indetermined IGRA results were observed in 4/123 (3.3%) patients. CXCL-10/IP-10 positive results were seen in 39/123 (39.8%) patients. Multivariate regression analysis identified that non-vaccination with BCG (aOR 7.41 [CI 2.15-25.48]; p = 0.0014) and the positivity for CXCL-10/IP-10 assay (aOR 4.48 [CI 1.87-10.76]; p = < 0.001) were independent risk factors for LTBI among DRC and HD patients. The IGRA QFT-Plus was shown to be a useful method in the surveillance of LTBI in critical stages of CKD and routine hemodialysis. Mtb-specific CXCL-10/IP-10 responses were associated with a positive IGRA and could provide an useful adjuvant biomarker of LTBI in this population.