Complement activation products in idiopathic pulmonary fibrosis: relevance of fragment Ba to disease severity.

Immune complexes have been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a chronic inflammatory disease of unknown etiology. Using newly developed techniques to measure complement fragments, we assessed whether complement activation occurs in IPF and its relationship to circulating immune complexes (CIC), disease severity, and prognosis. We measured the fragments C3d, C4d, and Ba of the common, classical, and alternative pathway, respectively, along with the components C3, C4, and Factor B and CIC, in 18 patients and 19 healthy subjects. The fragment to parent molecule ratios C3dC3, C4dC4, and Ba/Factor B were derived. Complement determinations were repeated in 14 of the patients on a second occasion separated by 8–33 months (median 17 months) from the first. All parameters were higher in patients than controls, and the difference between the two groups was significant for C3d, C4dC4, C3, CIC (P < 0.05) and for C4d and Ba (P < 0.01). Fragment Ba was found to correlate with disease duration and indices of disease severity, i.e., positively with the dyspnoea score (RS = 0.44, P < 0.04), the physiological score (RS = 0.50, P < 0.02), the fibrosis score (RS = 0.45, P < 0.04), and a composite clinical, radiological, and physiological score (RS = 0.48, P < 0.03) and negatively with the forced vital capacity (RS = −0.47, P < 0.03). Ba was higher in those patients who deteriorated on follow-up analysis than those who improved or remained unchanged (P < 0.04). These results show that conversion products of all complement pathways are increased in IPF and demonstrate classical pathway activation. They also show that the measurement of Ba might prove a useful laboratory test of disease severity in this condition.