Viegas, S. | Search bioRxiv

bioRxiv2025

Imbalance of Tregs/B cells and elevated complement signalling are hallmarks of Refractory Myasthenia Gravis

BackgroundA significant proportion of patients with myasthenia gravis (MG) remain refractory to standard immunosuppressive therapy, and biomarkers to help guide treatment decisions are lacking. MethodsWe examined the circulating immune profile of patients with acetylcholine receptor antibody positive MG with differing treatment requirements and compared them to controls. FindingsRefractory patients displayed the highest frequency of memory B cells, and increased production of interleukin (IL)-6 and tumour necrosis factor (TNF)- upon toll-like receptor/ CD40 activation in vitro, mirrored by a dramatic loss of regulatory T cells (Tregs) and dendritic cells. Refractory MG was further characterised by elevated circulating complement proteins (C3, C5 and clusterin) and increased expression of complement receptors on lymphocytes. Following anti-CD20 therapy, residual plasmablasts persisted in circulation. Notably, a low baseline B cell frequency (<3%) was associated with poor clinical response to rituximab in refractory disease, although the sample size was limited. ConclusionOur findings define a distinct immune signature in refractory MG, identify potential biomarkers of treatment resistance, and highlight plasma cell depletion, IL-6 or complement inhibition, and Treg expansion as promising therapeutic avenues. FundingFunding was received from the NorthCare Charity, Myaware, Academy of Medical Sciences and the Neuromuscular Study Group. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/643341v3_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@13df9e2org.highwire.dtl.DTLVardef@1e086eborg.highwire.dtl.DTLVardef@1b9bb92org.highwire.dtl.DTLVardef@c9a164_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2019

Improving diagnosis and monitoring of treatment response in pulmonary tuberculosis using the molecular bacterial load assay (MBLA)

ObjectivesBetter outcomes in tuberculosis require new diagnostic and treatment monitoring tools. In this paper we evaluated the utility of a marker of M. tuberculosis viable count, the Molecular Bacterial Load assay (MBLA) for diagnosis and treatment monitoring of tuberculosis in a high burden setting. MethodsPatients with smear positive pulmonary tuberculosis from two sites in Tanzania and one each in Malawi and Mozambique. Sputum samples were taken weekly for the first 12 weeks of treatment and evaluated by MBLA and mycobacterial growth indicator tube method (MGIT). ResultsThe results of high and low positive control samples confirmed inter site reproducibility. Over the 12 weeks of treatment there was a steady decline in the viable bacterial load as measured by the MBLA that corresponds to rise in time to a positive result (TTP) in the Mycobacterial Growth Indicator Tube. Both MBLA and MGIT provided similar time to test negativity. Importantly, as treatment progressed samples in MGIT were increasingly likely to be contaminated, which compromised the acquisition of results but did not affect MBLA samples. ConclusionsMBLA produces a reproducible measure of Mtb viable count comparable to that of MGIT that is not compromised by contamination in a real-world setting. As a molecular test, the results can be available in as little as four hours and could allow health care professionals to identify rapidly patients who are failing therapy.

microbiology↗