Zeitschrift für klinische und zelluläre Immunologie
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Deficiency of Mannose Associated Serine Protease2 (MASP2) in Patients with Idiopathic Pulmonary Fibrosis

Varney VA, Parnell H, Quirke G, Bansal A, Sumar N, Nicholas A and Evans J

Background: Idiopathic pulmonary fibrosis (UIP/IPF) is increasing. The condition occurs both sporadically and in close blood relatives suggesting a genetic predisposition. Histology suggests that the fibrosis is linked to disordered apoptosis, but the causal agent is so far unrecognised. We previously published evidence of mannose binding lectin deficiency (MBL) in early onset disease and in those with a family history of UIP/IPF. MBL is part of the innate immune system with levels genetically determined. MBL activation is impaired if the mannose associated serine protease2 (MASP2) is severely deficient in the serum (levels<100 ng/ml). The MBL/MASP2 complex is involved in phagocytosis, complement activation and clearance of apoptotic cells. Levels of MASP2 are genetically determined and not influenced by inflammation.
Aims and Method: We examined plasma MASP2 levels in healthy controls (HC) and in patients with frequently exacerbating COPD, pulmonary TB and sarcoid along with UIP/IPF including those with or without a family history.
Results: Mean serum MASP2 levels were lowest in those with UIP/IPF (304 ng/ml) compared with healthy controls (537 ng/ml), COPD (1090 ng/ml), TB (659 ng/ml) and sarcoid (385 ng/ml). Chisquare analysis for the frequency of severe MASP2 deficiency (<100 ng/ml versus >100 ng/ml) showed no differences between Healthy Controls, COPD, TB and sarcoid. UIP/IPF showed a significant increase in the frequency of severe deficiency. This was seen for early onset disease<55yrs (33% p=0.0001), late onset>55yrs (20% p=0.0001) and those with a family history (19% p=0.0143). The expected frequency for the Caucasian population is <1%.
Conclusion: The data shows that severe MASP2 deficiency is seen in our UIP/IPF patients and is highest in those with early onset disease. For TB and Sarcoid there is an increased frequency of deficiency (67%) compared with healthy controls (3%): and these diseases can also give fibrotic scarring to the lung. Since MASP2 levels<100 ng/ml are considered to cause impaired function of the lectin pathway it could have relevance to complement activation, apoptosis and fibrosis in this disease.