Serum complement component C1q levels in Quantiferon positive uveitis: improved stratification of high versus low risk active tuberculosis?

Abstract

Purpose : Rapid initiation of anti-tuberculosis treatment (ATT) in patients suffering from active tuberculosis (TB) associated uveitis is crucial to obtain optimal visual outcomes. We previously identified a type-1 interferon transcriptional signature (IFN-sig) associated with active pulmonary tuberculosis (APTB). This signature may be useful to stratify QuantiFERON-TB Gold test (QFT)⁺ uveitis patients into those with a high or low probability of an active TB infection. A study by Lubbers et al. found an association between elevated serum C1q levels and APTB, and consequently proposed serum C1q as a marker for active TB. Therefore, we determined serum C1q levels in APTB, QFT⁺ uveitis of unknown etiology and QFT^- uveitis patients, and compared this with the IFN-sig.

Methods : Sera from 12 uveitis patients with APTB, 58 QFT⁺ patients with uveitis of unknown etiology and 51 QFT^- uveitis patients were included. Also, sera from 10 APTB patients without uveitis, and 23 QFT^- healthy controls (HC) were included. Serum C1q levels were determined by ELISA.

Results : Serum C1q levels were significantly increased in patients with APTB as well as in QFT⁺ uveitis patients of unknown etiology as compared to HC. While serum C1q levels of QFT^- uveitis patients did not differ from HC (Fig. 1A). APTB patients with uveitis displayed significantly higher serum C1q levels than APTB patients without uveitis (Fig. 1B). Pearson’s r revealed an inverse correlation between serum C1q levels in APTB patients with the IFN-sig (Fig. 1C).

Conclusions : We confirmed the reported association between increased serum C1q levels and APTB. Serum C1q levels were further increased in APTB patients with uveitis. Here, we propose a two-step analysis to stratify QFT⁺ patients into groups with low or high risk of active TB-induced uveitis. First, the IFN-sig is determined, a positive signature is indicative of active infection. Subsequently, serum C1q levels are determined in patients with a negative IFN-sig. Levels above the upper limit of the 95% probability interval of the HC are indicative of an active infection. Patients with a negative IFN-sig and low serum C1q levels are considered at low risk of suffering from active TB-induced uveitis. In these patients it might be more appropriate to monitor disease development instead of direct initiation of toxic ATT.

This is a 2020 ARVO Annual Meeting abstract.