03081nas a2200337   4500000000100000008004100001653003600042653001900078653001200097653002200109100001300131700001200144700001700156700001400173700001800187700001800205700001600223700001500239700001300254700001200267700001100279700001400290700001300304700001500317245013800332856009900470300001300569490000700582520214000589022001402729       2019                            d10aErythema nodosum leprosum (ENL)10aimmunoglobulin10aleprosy10aReversal reaction1 aAmorim F1 aNobre M1 aNascimento L1 aMiranda A1 aMonteiro GR G1 aFreire-Neto F1 aQueiroz MCP1 aQueiroz JW1 aDuthie M1 aCosta M1 aReed S1 aJohnson W1 aDupnik K1 aJeronimo S00aDifferential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum.  uhttps://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0007089&type=printable  ae00070890 v133 a<p><strong>BACKGROUND: </strong>Leprosy is a treatable infectious disease caused by Mycobacterium leprae. However, there is additional morbidity from leprosy-associated pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. There is currently no predictive marker in use to indicate which people with leprosy will develop these debilitating immune reactions. Our peripheral blood mononuclear cell (PBMC) transcriptome analysis revealed that activation of the classical complement pathway is common to both RR and ENL. Additionally, differential expression of immunoglobulin receptors and B cell receptors during RR and ENL support a role for the antibody-mediated immune response during both RR and ENL. In this study, we investigated B-cell immunophenotypes, total and M. leprae-specific antibodies, and complement levels in leprosy patients with and without RR or ENL. The objective was to determine the role of these immune mediators in pathogenesis and assess their potential as biomarkers of risk for immune reactions in people with leprosy.</p>

<p><strong>METHODOLOGY/FINDINGS: </strong>We followed newly diagnosed multibacillary leprosy cases (n = 96) for two years for development of RR or ENL. They were compared with active RR (n = 35), active ENL (n = 29), and healthy household contacts (n = 14). People with leprosy who subsequently developed ENL had increased IgM, IgG1, and C3d-associated immune complexes with decreased complement 4 (C4) at leprosy diagnosis. People who developed RR also had decreased C4 at leprosy diagnosis. Additionally, elevated anti-M. leprae antibody levels were associated with subsequent RR or ENL.</p>

<p><strong>CONCLUSIONS: </strong>Differential co-receptor expression and immunoglobulin levels before and during immune reactions intimate a central role for humoral immunity in RR and ENL. Decreased C4 and elevated anti-M. leprae antibodies in people with new diagnosis of leprosy may be risk factors for subsequent development of leprosy immune reactions.</p>
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