Arginase 1 is a marker of protection against illness in contacts of leprosy patients

Abstract

Leprosy household contacts are generally more prone to develop the disease compared to the general population. Previous studies have demonstrated that genes related to the alternative activation (M2) profile in macrophages are associated with the increased bacillary load in multibacillary leprosy patients (MB), and that contacts of MB patients have a higher risk of contracting the disease. In addition, positive serological responses to PGL-1 or LID-1 are associated with a higher risk of disease. We performed a 5-year follow-up of contacts of leprosy patients and evaluated the pattern of gene and protein expression in cells from contacts that developed leprosy during this period. Leprosy household contacts had decreased soluble CD163 and heme oxygenase 1 (HO-1) serum levels when compared with healthy donors and leprosy patients. In contrast, arginase 1 activities were higher in contacts when compared with both healthy donors and leprosy patients. Of the contacts, 33 developed leprosy during the follow-up. Gene expression analysis revealed reduced ARG1 expression in these contacts when compared with contacts that did not develop disease. Arginase activity was a good predictive marker of protection in contacts (sensitivity: 90.0%, specificity: 96.77%) and the association with serology for anti-PGL-1 and anti-LID-1 increased the sensitivity to 100%. Altogether, the data presented here demonstrate a positive role of arginase against leprosy and suggest that the evaluation of arginase activity should be incorporated into leprosy control programs in order to aid in the decision of which contacts should receive chemoprophylaxis.

Figure 1

Contacts of leprosy patients present higher arginase activity than healthy controls and patients. Serum from healthy donors of endemic areas (HD, n = 18), paucibacillary patients (PB, n = 42), multibacillary patients (MB, n = 59), household contacts of PB patients (HC-PB, n = 58), and household contacts of MB patients (HC-MB, n = 83) were collected and levels of soluble (A) CD163 and (B) HO-1 were evaluated by ELISA. In addition, (C) arginase activity was evaluated. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.

Figure 2

Arginase activity is associated with protection against leprosy in contacts. Whole blood cells and serum from 141 contacts were evaluated. Of these contacts, 33 developed leprosy during the follow-up (HC-DD). HC-NDD, household contacts that did not develop disease. (A) HMOX1 expression, (B) HO-1 levels in sera, (C) ARG1 expression and, (D) arginase activity. *p ≤ 0.05, ****p ≤ 0.0001.

Figure 3

Evaluation of HO-1 and Arginase as predictive markers of illness in leprosy contacts. Receiver operating characteristic curves (ROC) for contacts showing the two markers tested (HO-1, red and Arginase, blue).