03258nas a2200277   4500000000100000008004100001260003200042653001800074653002000092653002200112653001700134653001200151100002100163700001700184700001100201700001600212700001300228700001500241700001900256245011900275856009200394300001100486490000700497520246200504022001402966       2026                            d  c06/2026bFrontiers Media SA10aTranscriptome10aImmune response10aImmune regulation10aSm29 antigen10aleprosy1 aKaroline Silva J1 ade Farias LN1 aLago T1 aCardoso LDS1 aKhouri R1 aMachado PR1 aCastellucci LC00aThe Sm29 antigen differentially shapes transcriptomic and regulatory landscapes across reactional forms of leprosy  uhttps://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1844112/pdf  a1 - 130 v173 a<p><strong>Background</strong></p>

<p>It is documented that Schistosoma mansoni antigens can induce immune responses able to regulate complex diseases. Conversely, the dysregulated inflammatory response in leprosy increases morbidity and leads to reactional episodes, impairing the disease pathogenesis. The goal of this study was to evaluate the potential of the S. mansoni (Sm29) antigen in regulating the immune response in leprosy through a transcriptome study across clinical reactional forms: reversal reaction (RR), and erythema nodosum leprosum (ENL), and without reaction (WR).</p>

<p><strong>Methods</strong></p>

<p>Peripheral blood mononuclear cells (PBMCs) were cultured and stimulated with sonicated M. leprae antigen and rSm29 antigen. Total RNA was extracted by the TRIzol ® (Ambion) according to the manufacturer’s protocol. RNA libraries were constructed with the TruSeq Stranded Total RNA Prep Globin kit (Illumina) and quantified by qPCR with the KAPA Library Quantification Kit (Roche). Sequencing was performed by Nextseq 2000 (Illumina) with 2x100 base pairs (bp) reads. Differential expression was analyzed using DESeq2 to identify differentially expressed genes (DEGs) between conditions. Identified DEGS were subjected to Ingenuity Pathway Analysis (IPA)for enrichment pathway analysis.</p>

<p><strong>Results</strong></p>

<p>The Sm29 antigen was able to modulate immune response pathways in leprosy, with this response being more pronounced in the reactional forms of the disease, especially in RR. Interestingly, when compared to sonicated M. leprae , Sm29 had an opposite effect in RR-ENL, evidenced by the top genes most expressed in RR and less in the ENL ( C2CD4B, CEMIP, IL23A, CD7, GPC5, EBF1, SIGLEC15, ADAT2, ZC3H12D ); Additionally, IPA analysis shown that in RR, modulation of the CSF2 by Sm29 increases IL10 , while modulation by IFN-α modulates CXCL9, CXCL-10, IL15, TLRs 2 and 4 ; On the other hand, in ENL, modulation of IL1B and FN1 genes by rSm29 appear related to several chemokines and cytokines such as IL6, CCL2 and CXCL8 .</p>

<p><strong>Conclusion</strong></p>

<p>Leprosy proves to be an efficient model for investigating products capable of regulating the host inflammatory response. Here, we open perspectives for new insights in the use of immunobiological, expanding attention to this field that might help management of leprosy patients, especially in reactional episodes.</p>
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