Identification and characterization of Loa loa antigens responsible for cross-reactivity with rapid diagnostic tests for lymphatic filariasis

• Published in: PLoS neglected tropical diseases 2018-11, Vol.12 (11), p.e0006963-e0006963
• Main Authors: Hertz, Marla I, Nana-Djeunga, Hugues, Kamgno, Joseph, Jelil Njouendou, Abdel, Chawa Chunda, Valerine, Wanji, Samuel, Rush, Amy, Fischer, Peter U, Weil, Gary J, Budge, Philip J
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Helminth - blood; Antibodies, Helminth - immunology; Antigen-antibody reactions; Antigens; Antigens, Helminth - blood; Antigens, Helminth - immunology; Biology; Biology and Life Sciences; Blood; Blood circulation; Carbohydrates; Care and treatment; Cross Reactions; Cross-reactivity; Diagnosis; Diagnostic systems; Diagnostic tests; Diagnostic Tests, Routine; Elephantiasis, Filarial - blood; Elephantiasis, Filarial - diagnosis; Elephantiasis, Filarial - immunology; Elephantiasis, Filarial - parasitology; Endemic species; Female; Filariasis; Glycoproteins; Helminth Proteins - genetics; Helminth Proteins - immunology; Hostages; Humans; Immunoglobulins; Infectious diseases; Loa - genetics; Loa - immunology; Loa loa; Medical tests; Medicine; Medicine and Health Sciences; Molecular weight; Monoclonal antibodies; Nematodes; Parasites; Parasitology; Proteins; Reactivity; Research and Analysis Methods; Risk factors; Tests; Tropical diseases; Vector-borne diseases; Wuchereria bancrofti - genetics; Wuchereria bancrofti - immunology; Wuchereria bancrofti - isolation & purification
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0006963

The Global Program to Eliminate Lymphatic Filariasis (LF) relies on rapid diagnostic tests (RDTs) to determine where annual mass drug administration for LF is required and when it can be stopped. These tests detect a Wuchereria bancrofti glycoprotein in the blood of infected persons via a carbohydrate moiety recognized by the monoclonal antibodies AD12 and DH6.5. Loiasis cross-reactivity with LF RDTs has recently been recognized as a serious obstacle to LF elimination in loiasis-endemic areas. To better understand the nature of this cross-reactivity, we used the DH6.5 antibody to immunoaffinity purify Loa loa antigens from the sera of individuals with a positive RDT due to loiasis. Immunoblot analysis revealed many circulating AD12/DH6.5-reactive antigens, and proteomic analysis identified multiple L. loa proteins in LF RDT-positive loiasis sera. These included both secreted and somatic proteins, suggesting that they may be released by dying L. loa adult worms and/or microfilariae. Unlike the single high molecular weight W. bancrofti circulating filarial antigen that is reliably present in the blood of persons with bancroftian filariasis, reactive L. loa antigens appeared to be only transiently present in the blood of a subset of persons with loiasis. These key differences between the circulating antigens of W. bancrofti and L. loa can be used to differentiate positive results generated by both species and may lead to improved diagnostic tests for LF and loiasis.