Inverse correlation between serum complement component C1q levels and whole blood type-1 interferon signature in active tuberculosis and QuantiFERON-positive uveitis: implications for diagnosis

Objectives: To examine the relation between serum C1q levels and blood type-1 interferon signature (type-1 IFN signature) in active pulmonary tuberculosis (APTB) and to determine whether combined measurement of serum C1q and type-1 IFN signature may add to the diagnosis of QuantiFERON-positive (QFT⁺) patients with uveitis of unknown cause. Methods: C1q was determined (ELISA) in serum from two distinct Indonesian cohorts, and in total, APTB (n = 72), QFT⁺ uveitis of unknown aetiology (n = 58), QFT⁻ uveitis (n = 51) patients and healthy controls (HC; n = 73) were included. The type-1 IFN signature scores were previously determined. Results: Serum C1q was higher in APTB than HC (P < 0.001). APTB patients with uveitis had higher serum C1q than APTB patients without uveitis (P = 0.0207). Serum C1q correlated inversely with type-1 IFN signature scores in APTB (P = 0.0036, r² = 0.3526), revealing that these biomarkers for active TB disease can be mutually exclusive. Stratification of QFT⁺ patients with uveitis of unknown cause, by serum C1q and type-1 IFN signature, yielded four groups with different likelihood of suffering from active TB uveitis. Conclusion: Serum C1q is elevated in APTB, especially in those cases with uveitis. We propose that combined measurement of blood type-1 IFN signature and serum C1q may provide added value in the diagnosis of active TB disease. Combined measurement of type-1 IFN signature and serum C1q in QFT⁺ patients without signs of active TB disease, but suffering from uveitis of unknown cause, may be of help to identify cases with low or high likelihood of having active TB uveitis, which may facilitate clinical management decisions.