Immuno

Rheumatoid arthritis (RA) is triggered by dysregulated cytokine networks, but the distributional association of conventional synthetic (csDMARDs) and biologic DMARDs (bDMARDs) with circulating mediators has not been fully described. In this study, we aimed to investigate the treatment-associated modulation of TNF-α, IL-17, IL-13, and soluble CTLA-4 (sCTLA-4) in 64 RA patients (untreated, n = 14; csDMARD, n = 32; bDMARD ± csDMARD, n = 18) and 20 controls. ELISA was used to determine the serum levels, and Kruskal–Wallis tests and false discovery rate correction were used to determine the differences between groups, accompanied by DAS28- and CRP-adjusted quantile regression. Group-level analysis demonstrated that the levels of IL-17 were higher in patients treated with csDMARDs and bDMARDs than in the controls (FDR-adjusted p = 0.0009 and <0.0001, respectively), and the levels of IL-13 were higher in patients treated with bDMARDs than in the controls (p = 0.026). However, quantile regression did not reveal consistent treatment-related associations, suggesting that long-term pathway-specific immune responses and context-dependent regulation may be involved. Smoking independently predicted higher IL-13 at lower quantiles (β = 35.5; p < 0.0001), while TNF-α showed treatment-related increases only at the upper quantile in CRP-adjusted models (β = 323.7; p = 0.049). On the other hand, sCTLA-4 had the largest and most significant treatment-based increase (p < 0.0001), regardless of disease activity, and constant effects across mid-quantiles. Taken together, these findings suggest that sCTLA-4 shows therapy-responsive distributional changes, supporting its potential utility as a biomarker of biological efficacy. In contrast, the observed increases in IL-17 and IL-13 reflect ongoing immune activity and possible environmental influences. Distribution-sensitive biomarker profiling provides a nuanced approach to capturing immune response diversity in RA and may enhance precision in monitoring procedures.

The balance of alveolar macrophage (AM) polarization is severely disrupted in chronic inflammatory diseases like bronchiectasis, where a persistent pro-inflammatory (M1) phenotype perpetuates inflammation. To address this, we developed a high-throughput platform using a series of synthetic glycoligands (L1-L5) on a polyethyleneimine (PEI) scaffold. These ligands, which have varying affinities for macrophage lectin-like receptors, were used for phenotypic “fingerprinting” of AM subpopulations from pediatric bronchiectasis patients and a healthy control. Analysis of bronchoalveolar lavage fluid (BALF) revealed a pathogenic, M1-dominant profile (55% M1) in patients, confirming a state of chronic inflammation, which starkly contrasted with the quiescent, M0-dominant profile in the healthy control. We then leveraged this platform for targeted immunomodulation, using a drug-ligand conjugate to steer the dysregulated macrophage population toward a healthy state. The most potent conjugate, Dox-L5, dramatically suppressed the pathogenic M1 population (from 55% to 16%). This M1 suppression was accompanied by a significant shift toward the M2a (tissue-repair) phenotype and the emergence of a quiescent M0-like population, effectively remodeling the AM profile. This work validates a glycan-based platform for both diagnosing and correcting pathological macrophage imbalances. Our targeted approach offers a precise strategy to resolve chronic inflammation in bronchiectasis by suppressing M1 macrophages and promoting a pro-resolving M0/M2 phenotype, thereby restoring lung homeostasis.

Chagas disease, caused by Trypanosoma cruzi, affects a significant proportion of patients who develop digestive and cardiac complications, including megaviscera. This pathogenesis has been associated with autoimmune mechanisms mediated by molecular mimicry. In this study, an in silico evaluation of the potential structural basis of cross-reactivity of β-tubulin 1.9 of T. cruzi and the human β-4A tubulin isoform 3 was conducted. Using bioinformatics tools, homologous regions were identified and potentially immunogenic epitopes were predicted, considering their structural modeling and molecular docking. The proteins shared 87% sequence identity and 95% similarity, with an almost identical structural overlap, RMSD 0.291 Å. Three epitopes, VPFPRLHFF, NDLVSEYQQYQDATI, and GQSGAGNNWAKGHYTEGAELIDS, exhibited high predicted antigenicity, with the 9-mer and 16-mer peptides displaying structurally compatible docking poses within the binding grooves of MHC class I and class II molecules, respectively, while B-cell epitope potential was inferred from sequence-based property predictions. Normal mode analysis, used as an exploratory approach, suggested comparable flexibility profiles for the parasitic- and human-derived peptide–MHC complexes. These findings provide an exploratory structural framework supporting a potential role of β-tubulin epitopes in molecular mimicry processes implicated in the development of chagasic megaviscera.