Circulating IP-10/CXCL10 Correlates With Parasitemia and Disease Severity in Patients With Babesiosis: A Pilot Study
Miranda S Oakley, Clifford T H Hayashi, Anne Spichler-Moffarah, Victoria Majam, Marjorie Golden, Scott Meredith, Hong Zheng, David E Leaf, Audrey Monson, Scott C Roberts, Demerise Johnston, Peter J Krause, Sanjai KumarAbstract
Background
Human babesiosis is an emerging tick-borne zoonosis that can cause serious complications, including death. Immune mechanisms that confer protection or promote disease severity in human babesiosis are poorly understood.
Methods
We measured the cytokine and antibody profile in a cohort of hospitalized patients who had babesiosis. Cytokine levels were measured in plasma using the Bio-Plex Pro Human Cytokine 27-Plex Assay, and Babesia microti–specific total IgG and its 4 isotypes were measured using an immunofluorescence assay. Cytokine profile was analyzed in relation to immune status, peak parasitemia, lowest hemoglobin levels, and disease severity.
Results
There were enhanced levels of 8 cytokines (eotaxin, IL-6, IL-8, IL-10, IP-10/CXCL10, MCP-1, MIP-1α, and TNF-α) in the plasma of 16 patients with babesiosis as compared with 7 controls. A positive correlation was found between IP-10 levels and parasitemia (Spearman R = 0.52, P = .04). Patients with severe babesiosis had elevated levels of IP-10 and IL-5 as compared with the other 2 clinical categories (ie, moderate and moderately severe). Immunosuppression was associated with low levels of the VEGF and FGF basic angiogenic factors. There was also an inverse correlation between hemoglobin and IL-1β or IL-9 levels. Last, patients with babesiosis produced abundant levels of immunofluorescence assay total IgG and IgG1 and IgG3 but low levels of IgG2 and no IgG4.
Conclusions
IP-10 and other cytokines that exhibited elevated levels should be further investigated as biomarkers of severe babesiosis.