Identification of CD163 as an antiinflammatory receptor for HMGB1-haptoglobin complexes

Original citation: JCI Insight. 2016;1(7):e85375. https://doi.org/10.1172/jci.insight.85375

Citation for this corrigendum: JCI Insight. 2018;3(24):e126617. https://doi.org/10.1172/jci.insight.126617

The Editors posted an Expression of Concern for this article following notification that an investigative committee at the University of Liverpool had data integrity concerns regarding the NMR experiments contributed by Daniel J. Antoine, shown in Figure 1, E and F. The Journal has published a corrected version of this article, and the authors have provided a description of changes, which is below:

In our published work, we reported that HMGB1 binds to haptoglobin, the acute phase protein that binds extracellular hemoglobin. We based our conclusions on multiple lines of evidence: (a) haptoglobin-conjugated beads captured HMGB1 after hemoperfusion of septic rats (Figure 1A); (b) immune-precipitation assays using pure proteins confirmed binding of haptoglobin and HMGB1 (Figure 1B); (c) surface plasmon resonance analysis (BIACore) using pure proteins revealed the binding interaction of haptoglobin and HMGB1 had an affinity (Kd) around 64 nM (Figure 1C); (d) there are three redox isoforms of HMGB1. We showed that haptoglobin effectively binds fully reduced and disulfide isoforms of HMGB1, but not the fully oxidized sulfonyl HMGB1, as revealed by immune-precipitation assay (Figure 1D); and (e) we observed HMGB1-haptoglobin complexes in human serum from patients with severe sepsis by coimmunoprecipitation using haptoglobin-specific antibodies (Figure 1G in the original article; Figure 1E in the corrected article).

In Figures 1, E and F, an analysis of HMGB1 isoforms by NMR was undertaken in a separate laboratory by Daniel J. Antoine. In November 2018, we learned that these data were likely compromised. We contacted the Journal, and the Editorial Board agreed to publish an updated online version of the article. In the updated version, all conclusions based on Figure 1, E and F, have been removed. The Journal has also published an online version of the original article with the unreliable statements crossed out (Supplemental File, Redaction). We believe that the major conclusions of the study are accurate and that the corrected paper is reliable.

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Footnotes

See the related article at Identification of CD163 as an antiinflammatory receptor for HMGB1-haptoglobin complexes.