Utility of HACOR Score in Patients with Acute Exacerbation of Post-tuberculosis Obstructive Airway Disease: A Retrospective Observational Study.

OBJECTIVE: In this study, we tried to analyze the utility of the HACOR score in the acute exacerbation of post-tuberculosis obstructive airway disease (post-TB-OAD). MATERIALS AND METHODS: The HACOR score for patients in acute exacerbation of post-TB-OAD who needed noninvasive ventilation (NIV) support was calculated at 1, 12, 24, and 48 hours. The history of NIV success or failure was noted. Using a cutoff score of >5, the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. The receiver operating characteristic (ROC) curve was plotted based on the HACOR score 1 hour after the NIV trial. In subjects requiring NIV for up to 2 days, the trend in the HACOR score was analyzed using a paired t-test. RESULTS: A total of 38 out of 100 patients belonged to the NIV failure group. The mean HACOR score at 1 hour was 9.47 in the NIV failure group. The sensitivity was 89.47%, and the specificity was 87.09% for a score of >5. The positive predictive value and negative predictive value were 80.95 and 93.10%, respectively. The area under the curve (AUC) for the ROC was 0.853. The mean score showed an upward trend in the NIV failure group and a downward trend in the NIV success group. The change in the score in the NIV success group was statistically significant (t = -4.290, p-value = 0.00044). CONCLUSION: The HACOR score can predict NIV failure in patients with acute exacerbation of post-TB-OAD.

Disrupted degradative sorting of TLR7 is associated with human lupus.

Hyperactive TLR7 signaling has long been appreciated as driver of autoimmune disease in mouse models. Recently, gain-of-function mutations in TLR7 were identified as a monogenic cause of human lupus. TLR7 is an intracellular transmembrane receptor, sensing RNA breakdown products within late endosomes. Here, we show that endosome dysfunction leads to unrestricted TLR7 signaling and is associated with human lupus. The late endosomal BORC complex together with the small GTPase Arl8b controls intracellular TLR7 levels by regulating receptor turnover. This requires a direct interaction between the TLR7-associated trafficking factor Unc93b1 and Arl8b. We identified an UNC93B1 mutation in a patient with childhood-onset lupus, which results in reduced BORC interaction and endosomal TLR7 accumulation. Therefore, a failure to control TLR7 turnover is sufficient to break immunological tolerance to nucleic acids. Our results highlight the importance of an intact endomembrane system in preventing pathological TLR7 signaling and autoimmune disease.