Glycosylation profile of Mycobacterium leprae-specific antibodies associated with disseminated infection

Leprosy still affects hundreds of thousands of new patients each year and can result in permanent nerve damage if not treated timely. Mycobacterium leprae -specific antibodies directed against the major cell-wall component, phenolic glycolipid-I (PGL-I), are associated with disseminated infection, suggesting that these antibodies do not provide adequate protection. Despite widespread use in diagnostic applications, the exact function of anti-PGL-I antibodies remains unknown. Therefore, antibody subclass distribution and Fc glycosylation of total and PGL-I-specific IgG were assessed by liquid chromatography-mass spectrometry, including leprosy patients from outpatient clinics in the Netherlands ( n = 160) and Brazil ( n = 55). The Fc domain of PGL-I-specific IgG1, the predominant subclass observed, showed elevated fucosylation, in combination with reduced sialylation and galactosylation. This distinctive glycoprofile of PGL-I specific IgG is generally linked to dampened effector functions, and points toward poor activation of effector mechanisms by these M. leprae- specific antibodies associated with disseminated infection.