IP-10 measured by Dry Plasma Spots as biomarker for therapy responses in Mycobacterium Tuberculosis infection

Abstract

Tuberculosis (TB) has huge impact on human morbidity and mortality and biomarkers to support rapid TB diagnosis and ensure treatment initiation and cure are needed, especially in regions with high prevalence of multi-drug resistant TB. Soluble interferon gamma inducible protein 10 (IP-10) analyzed from dry plasma spots (DPS) has potential as an immunodiagnostic marker in TB infection. We analyzed IP-10 levels in plasma directly and extracted from DPS in parallel by ELISA from 34 clinically well characterized patients with TB disease before and throughout 24 weeks of effective anti-TB chemotherapy. We detected a significant decline of IP-10 levels in both plasma and DPS already after two weeks of therapy with good correlation between the tests. This was observed both in pulmonary and extrapulmonary TB. In conclusion, plasma IP-10 may serve as an early biomarker for anti-TB chemotherapy responses and the IP-10 DPS method has potential to be developed into a point-of care test for use in resource-limited settings. Further studies must be performed to validate the use of IP-10 DPS in TB high endemic countries.

Individualizing management of extensively drug-resistant tuberculosis: diagnostics, treatment, and biomarkers

“…Therefore, although highly specific pathogen-derived biomarkers remain challenging to detect in all patients this combined with the lack of highly specific antibodies associated with TB infection is the main challenge for TB diagnostics. We suggest that the kinetics of relatively less specific host biomarkers in response to treatment may have advantages over monitoring pathogen-derived biomarkers for many patients [80][81][82].…”

Biomarcadores da tuberculose: uma revisão da literatura.

“…De forma similar um trabalho chinês (TONBY et al, 2015) pesquisou o comportamento da IP-10 em pacientes em regime quimioterápico. Não é possível avaliar com clareza se os resultados trazem padrões semelhantes ou distintos dos expostos por Chung et al (2016), devido os critérios particulares adotados por estes citados acima, contudo a IP-10 permaneceu responsiva a terapia com quedas notáveis no ponto de 8 semanas, assim como a conversão de grande parte dos pacientes em cultura negativa neste período de tempo presente nos dois trabalhos.…”

Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

“…Some of these biomarkers have the potential for point-of-care measurement, notably IP-10. [63,64] The clinical value for treatment optimization and the predictive power of these markers needs to be established in larger trials in different patient populations. To date, no biomarkers have been included in treatment evaluation.…”

“…TB is associated with increased serum IP-10 levels [93,[95][96][97], and at completion of therapy, levels are significantly lower than before treatment/at diagnosis. [64,98,99] This decrease is also measurable in the first weeks of therapy, [63,93] and therefore measurement of the kinetics of this cytokine during treatment may provide useful information on whether patients are responding to the prescribed drugs. It is also notable that host markers are present and detectable in all individuals.…”

“…Unlike bacterial-derived markers such as LAM, which is one of the most promising bacterial derived biomarkers, which are still undetectable in most infected patients. [100,101] In fact, IP-10 is a particularly interesting treatment response biomarker as it has been shown to be stable in dried plasma spots [64] and is present at high levels that are measurable with the new generation of simple near patient assays, [102] which should facilitate rapid repeated costs effective measurement. IP10, however, measured at a single-time point cannot specifically identify TB, nor distinguish between TB and latent-TB infection.…”