Distinct N-Linked IgG glycosylation profiles observed in Lymphatic filariasis

Distinct N-Linked IgG glycosylation profiles observed in Lymphatic filariasis

A group from Institute of Medical Microbiology, Immunology and Parasitology Institute for Medical Microbiology, University Hospital Bonn, Bonn, Germany, etc. has reported about distinct N-Linked IgG glycosylation profile observed in Lymphatic filariasis.

Lymphatic filariasis, commonly known as elephantiasis, is a tropical disease caused by vector-borne filarial parasites Wuchereria bancrofti, Brugia malayi, and Brugia timori. In endemic areas, most infected individuals remain asymptomatic, showing no external signs of the infection while bearing microfilaria (MF+) and contributing to the transmission of the parasite. In contrast, putatively immune individuals, also known as endemic normals (EN), remain infection-free despite continuous exposition to the vector. In some of the exposed individuals, the infection develops into chronic pathology (CP), manifesting as lymphoedema (tissue swelling), elephantiasis (skin/tissue thickening) of limbs, or hydrocele (scrotal swelling).

The clinical outcomes of the infection are tightly linked to the host’s immune reactivity. Typically, alongside classical parasite-induced Th2 immune responses, asymptomatic patients present a strong immune-regulated profile with high levels of regulatory cells, anti-inflammatory cytokines.

The Fc glycans in the IgG molecule are bi-antennary glycans with varying fucose content, bisecting N-acetylglucosamine (GlcNAc), galactose (Gal), and sialic acid; most IgG molecules are fucosylated. These glycan structures have profound impacts on antibody functions and thereby on health. Agalactosylated and asialylated IgG glycoforms, for example, were seen to be particularly abundant in chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease (IBD), HIV, and mycobacterial infections.

Distinct N-Linked IgG glycosylation profiles observed are as follows:
CP patients presented significantly more glycan residues compared to MF+ and EN,
IgG from EN presented the highest numbers of agalactosylated residues,
IgG from CP patients presented the highest levels of both mono- and bigalactosylated residues,
IgG from MF+ patients presented lower Level of afucosylation, higher Level of sialylated residues, and bisecting GlcNAc.

This study has identified clear differences in IgG glycan profiles between CP, MF+ individuals, and EN and suggests that IgG glycome alterations might potentially be useful as biomarkers for disease severity prediction in lymphatic filariasis.

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