25 Ago LEISHMANIA INFANTUM: HUMAN ASYMPTOMATIC INFECTION IN PATIENTS WITH CHRONIC RHEUMATIC DISEASES TREATED WITH BIOLOGIC AGENTS AND LIVING IN RURAL AREAS OF NORTHERN ITALY. MOLECULAR, IMMUNOLOGICAL AND METABOLOMICS ANALYSIS.
Molecular and immunologic data regarding Leishmania infantum asymptomatic infections are lacking. Aim of our study was: i) to assess the level of Li circulant kDNA in patients with chronic rheumatic diseases treated with biologic drugs and to correlate the positive detections to the area of residence; ii) to investigate the patient’s immune response and iii) to test novel compounds that can inhibit Li growth.
PBMC and sera from both 50 patients with inflammatory reumatisms and healthy controls were analyzed for Li kDNA (qPCR) and cytokines (Luminex technology), respectively. The activity of 6-aminonicotinamide against L. mexicana and L. infantum promastigotes was also investigated.
Among the 50 analyzed samples, 18 (36%) resulted positive for Li kDNA, with high parasite loads. Positive patients mainly come from rural areas and displayed higher cytokine levels of IL-12p70, IFN-γ, IL-2, TNF-α, IP-10, IL-10 and IL-13, compared to healthy controls. In both L. mexicana and L. infantum. 6-aminonicotinamide caused significant depletion in phosphoribosylpyrophosphate and nicotinate resulting in purine and pyrimidine nucleotides reduction.
The high parasitaemia detected in rheumatic patients suggests that biological drugs can lead to cryptic Li infection; consequently, molecular screening should be performed before starting with these drugs. 6-AN is responsible of depletion of cellular phosphoribosylpyrophosphate and lack of nucleotides required for nucleic acid biosynthesis of Li.