Hepcidin and conventional markers to detect iron deficiency in severely anaemic HIV-infected patients in Malawi.

Huibers, M. N.; Calis, J.; Allain, T. J.; Coupland, S. E.; Phiri, C.; Phiri, K.; Swinkels, D. W.; Boele van Hensbroek, M.; Bates, I.

doi:10.1101/666727

bioRxiv · 10.1101/666727

Hepcidin and conventional markers to detect iron deficiency in severely anaemic HIV-infected patients in Malawi.

Huibers, M. N.·Calis, J.·Allain, T. J.·Coupland, S. E.·Phiri, C.·Phiri, K.·Swinkels, D. W.·Boele van Hensbroek, M.·Bates, I.

View original source ↗Export metadata ↓

Abstract

IntroductionIron deficiency is a treatable cause of severe anaemia in low-and-middle-income-countries (LMIC). Diagnosing it remains challenging as peripheral blood markers poorly reflect bone-marrow iron deficiency (BM-ID), especially in the context of HIV-infection.\n\nMethodsSevere anaemic (haemoglobin [≤]70g/l) HIV-infected adults were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. BM-ID was evaluated. Accuracy of blood markers including hepcidin alongside mean corpuscular volume, mean cellular haemoglobin concentration, serum iron, serum ferritin, soluble transferrin receptor (sTfR), sTfR -index, sTfR-ratio to detect BM-ID was valued by ROC area under the curve (AUCROC).\n\nResultsSeventy-three patients were enrolled and 35 (48.0%) had BM-ID. Hepcidin and MCV performed best; AUCROC of 0.593 and 0.545. Other markers performed poorly (ROC<0.5). The AUCROC of hepcidin in males was 0.767 (sensitivity 80%, specificity 78%) and in women 0.490 (sensitivity 60%, specificity 61%).\n\nConclusionBM-ID deficiency was common in severely anaemic HIV-infected patients and is an important and potential treatable contributor to severe anaemia. Hepcidin was the best, though still suboptimal, marker of BM-ID. Hepcidin, which is directly linked to iron absorption, is a very promising marker to guide curative iron supplementation policies in severely anaemic HIV-infected patients.

Source connections

Published article ↗

Explore related subjects

biochemistry Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Huibers, M. N., Calis, J., Allain, T. J., Coupland, S. E., Phiri, C., Phiri, K., Swinkels, D. W., Boele van Hensbroek, M., Bates, I.. 2019-06-10. Hepcidin and conventional markers to detect iron deficiency in severely anaemic HIV-infected patients in Malawi.. https://doi.org/10.1101/666727

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Structural basis for inefficient G protein coupling by Frizzled receptors

Frizzleds (FZDs) are class F G protein-coupled receptors (GPCRs) that primarily signal through Dishevelled (DVL) to initiate Wnt signalling, with evidence for context-specific coupling to heterotrimeric G proteins. Every FZD-G protein structure to date has been determined without an agonist, implying that agonist binding is not required for stable complex formation in vitro and directly contradicting the difficulty of demonstrating G protein coupling in cells. All these structures contain unassigned density between the receptor and the heterotrimeric G protein. From structures generated by single-particle cryo-electron microscopy (cryo-EM) of FZD7-Gs and FZD5-Gq, we identify this density as the detergent lauryl maltose neopentyl glycol (LMNG), which bridges the receptor and G protein to stabilise a weak, shallow interface. Absence of LMNG - in biochemical preparations and molecular dynamics simulations - destabilises the complex, showing that constitutive FZD-G protein engagement is intrinsically weak. The weak G protein coupling is governed by a conserved intracellular interface that when mutated differentially influences DVL and G protein signalling. Our findings show that LMNG has masked the instability of purified FZD-G protein complexes and provide the structural basis of FZDs as inherently weak G protein activators that are predisposed to DVL signalling.

biochemistry↗

bioRxiv2026

A Binuclear Cluster Supports Functional Asymmetry in Dark-Operative Protochlorophyllide Reductase

Many photosynthetic bacteria rely on the nitrogenase-like dark-operative protochlorophyllide oxidoreductase (DPOR) to sustain (bacterio)chlorophyll synthesis in the dark. DPOR couples ATP hydrolysis to electron transfer from a reducing component (L-protein) to a catalytic component (NB-protein) that reduces protochlorophyllide. NB-protein is an 2{beta}2 heterotetramer, and each heterodimeric half contains an active site and a [Fe4S4] cluster. Although the two halves are identical, they react sequentially rather than in parallel. How the two halves communicate has remained unknown. Here we show, using Cu K-edge x-ray absorption spectroscopy and cryo-EM, that the NB-protein tetramer interface holds a binuclear, sulfur-bridged [Cu2S2] cluster. Each Cu is reduced and three-coordinate, with short Cu-S and Cu-Cu distances (2.26 and 2.62 &Aring). Mutagenesis excludes the nearest cysteine as the bridging ligand, supporting inorganic sulfide as the most likely sulfur donor. To our knowledge, this is the first sulfide-bridged dicopper cluster identified in a protein. The cluster is conserved in three purple non-sulfur bacteria and connects the BchB C-terminal helices that contact opposing active sites. Loss of Cu abolishes DPOR activity and asymmetric L-protein binding without disturbing overall fold. We propose that the cluster relays substrate-binding information between active sites, suggesting a metal-mediated mechanism for cooperativity in nitrogenase-like enzymes.

biochemistry↗

bioRxiv2026

Jade1S SUMOylates tau and targets oligomers for degradation

The accumulation of insoluble tau aggregates is a pathological hallmark of tauopathies, including Alzheimer's disease. While molecular chaperones and clearance pathways regulate tau homeostasis, the mechanisms governing tau oligomerization and degradation remain incompletely defined. Recent genome-wide association studies (GWAS) have linked the JADE1 locus to tauopathy, and the PHD zinc finger protein Jade1S has been identified in complexes with tau in post-mortem brain tissue, prompting investigation into their biochemical relationship. Here, we characterize the reciprocal interactions between Jade1S and 0N4R tau stability and turnover. Covalent labeling mass spectrometry and co-immunoprecipitation mappings reveal that Jade1S binds wild-type 0N4R tau through redundant sites within its N-terminal and plant homeodomain (PHD) zinc finger domains. In vitro assays demonstrate that Jade1S functions as a SUMO E3 ligase, utilizing its PHD domains to mediate tau SUMOylation. Cell-based cycloheximide chase assays reveal a reciprocal stabilization dynamic: tau co-expression extends the overall physiological half-life of Jade1S from less than an hour to ~17 hours, arresting its turnover specifically within sarkosyl-insoluble fractions. Conversely, Jade1S selectively accelerates the degradation of sarkosyl-insoluble tau without altering the turnover of the soluble monomeric pool over chased time. Mechanistically, Jade1S redirects the clearance of SUMO2/3-modified tau oligomers away from basal autophagic-lysosomal pathways and toward proteasome-dependent degradation. Furthermore, Jade1S exhibits intrinsic molecular chaperone activity, inhibiting arachidonic acid-induced tau oligomerization in vitro. Together, these data characterize Jade1S as a dual-function SUMO ligase and chaperone that regulates tau stability, prevents oligomer assembly, and promotes the targeted proteasomal clearance of aggregated tau.

biochemistry↗