Use of Protein Microarrays To Define the Humoral Immune Response in Leprosy Patients and Identification of Disease-State-Specific Antigenic Profiles

Abstract

Although the global prevalence of leprosy has decreased over the last few decades due to an effective multidrug regimen, large numbers of new cases are still being reported, raising questions as to the ability to identify patients likely to spread disease and the effects of chemotherapy on the overall incidence of leprosy. This can partially be attributed to the lack of diagnostic markers for different clinical states of the disease and the consequent implementation of differential, optimal drug therapeutic strategies. Accordingly, comparative bioinformatics and Mycobacterium leprae protein microarrays were applied to investigate whether leprosy patients with different clinical forms of the disease can be categorized based on differential humoral immune response patterns. Evaluation of sera from 20 clinically diagnosed leprosy patients using native protein and recombinant protein microarrays revealed unique disease-specific, humoral reactivity patterns. Statistical analysis of the serological patterns yielded distinct groups that correlated with phenolic glycolipid I reactivity and clinical diagnosis, thus demonstrating that leprosy patients, including those diagnosed with the paucibacillary, tuberculoid form of disease, can be classified based on humoral reactivity to a subset of M. leprae protein antigens produced in recombinant form.

Lateral flow assay for simultaneous detection of cellular- and humoral immune responses

“…Concentration values for unstimulated whole blood and PBMC cultures were typically ≤10 pg/ml. Anti-PGL-I IgM antibody levels were determined by ELISA as previously described [25]. …”

ML1419c Peptide Immunization InducesMycobacterium leprae-Specific HLA-A*0201–Restricted CTL In Vivo with Potential To Kill Live Mycobacteria

“…This response is primarily directed to PGL-I but also M. leprae protein antigens can be recognized by sera from lepromatous patients (30,31). In view of this, antibody levels against the ML1419c protein were analyzed after immunisation with its HLA-A*0201-restricted nonamer (Figure 3).…”

Biosensors as rapid diagnostic tests for tropical diseases

“…Protein microarrays 131 and phage display 132 have been used for such purpose, with the potential for discovery of new disease biomarkers. As many different peptide antigens are produced by the leprosy bacterium, leading to different antigenic responses in different individuals, 133 it is likely that a multiple-target assay would improve leprosy diagnosis.…”