Marker Panels For Idiopathic Pulmonary Fibrosis Diagnosis And Evaluation
The present invention relates to the discovery that of a panel of serum or plasma markers may be used to diagnose Idiopathic Pulmonary Fibrosis (“IPF”) and distinguish this condition from other lung ailments. It further relates to the identification of markers associated with IPF disease progression.
1 . A method of diagnosing idiopathic pulmonary fibrosis in a subject, comprising measuring the serum or plasma levels of a plurality of markers, wherein increases in the levels of MMP7, MMP1, and MMP8 as well as either or both of IGFBP1 and TNFRSF1A collectively indicate a diagnosis of idiopathic pulmonary fibrosis.
2 . The method of claim 1 , wherein increases in the levels of MMP7, MMP1 and MMP8 as well as either or both of IGFBP1 and TNFRSF1A have been determined, further comprising the step of confirming the diagnosis of idiopathic pulmonary fibrosis by a procedure selected from the group consisting of broncheoalveolar lavage and surgical lung biopsy.
3 . A method of diagnosing idiopathic pulmonary fibrosis in a subject, comprising measuring the serum or plasma levels of a plurality of markers, wherein increases in the levels of MMP7, MMP1, and MMP8 as well as either or both of IGFBP1 and TNFRSF1A, and a decrease in the level of AGER, collectively indicate a diagnosis of idiopathic pulmonary fibrosis.
4 . The method of claim 3 , wherein increases in the levels of MMP7, MMP1 and MMP8 as well as either or both of IGFBP1 and TNFRSF1A and a decrease in the level of AGER have been determined, further comprising the step of confirming the diagnosis of idiopathic pulmonary fibrosis by a procedure selected from the group consisting of broncheoalveolar lavage and surgical lung biopsy.
5 . A method of diagnosing idiopathic pulmonary fibrosis in a subject, comprising measuring the serum or plasma levels of a plurality of markers, wherein changes in the levels of MMP7, MMP 1, MMP8 and at least two markers selected from the group consisting of IGFBP1, TNFRSF1A, TNFRSF1B, MMP2, MMP3, AGER, CXCL10, CCL11, CCL2, FAS, IL12B, IL1RA, S100A12, B2M, MPO, ICAM-1, TF, VWF, SPA, SPD, and MUC1 (KL-6) collectively indicate a diagnosis of idiopathic pulmonary fibrosis.
6 . The method of claim 5 , wherein changes in the levels of MMP7, MMP1, MMP8 and at least two markers selected from the group consisting of IGFBP1, TNFRSF1A, TNFRSF1B, MMP2, MMP3, AGER, CXCL10, CCL11, CCL2, FAS, IL12B, IL1RA, S100A12, B2M, MPG, ICAM-1, TF, VWF, SPA, SPD and MUC1 (KL-6) have been determined, further comprising the step of confirming the diagnosis of idiopathic pulmonary fibrosis by a procedure selected from the group consisting of broncheoalveolar lavage and surgical lung biopsy.
7 . A method of identifying progression of idiopathic pulmonary fibrosis in a subject, comprising measuring the serum or plasma level of a marker selected from the group consisting of MMP7, DEFA-3, S100A12, and IL12P40, and a combination thereof, wherein an increase in the level of MMP7, an increase in the level of DEFA-1, an increase in the level of DEFA-2, an increase in the level of DEFA-3, an increase in the level of S100A12, and an increase in the level of IL12P40 indicate progression of idiopathic pulmonary fibrosis.
8 . The method of claim 7 , wherein an increase in the level of MMP7, an increase in the level of DEFA-1, an increase in the level of DEFA-2, an increase in the level of DEFA-3, an increase in the level of S100A12, and an increase in the level of IL12P40, has been determined, further comprising the step of recommending or performing a lung transplant.
9 . A kit for diagnosing idiopathic pulmonary fibrosis comprising means for determining the plasma levels of a panel of markers comprising MMP7, MMP1, and MMP8 as well as either or both of IGFBP1 and TNFRSF1A, wherein the set of markers MMP7, MMP1, MMP8 and IGFBP1 and/or TNFRSF1A constitute at least 30 percent of the total markers in the panel.
10 . A kit for diagnosing idiopathic pulmonary fibrosis comprising a means for determining the plasma levels of a panel of markers comprising MMP7, MMP1, MMP8 and AGER as well as either or both of IGFBP1 and TNFRSF1A, wherein MMP7, MMP1, MMP8, AGER and IGFBP1 and/or TNFRSF1A constitute at least 30 percent of the total markers in the panel.
11 . A kit for diagnosing idiopathic pulmonary fibrosis, comprising a means for determining the plasma levels of a panel of markers comprising MMP7, MMP1, MMP-8 and at least two markers selected from the group consisting of IGFBP1, TNFRSF1A, TNFRSF1B, MMP2, MMP3, AGER, CXCL10, CCL11, CCL2, FAS, IL12B, IL1RA, S100A12, B2M, MPO, ICAM-1, TF, VWF, SPA, SPD, and MUC1 (KL-6), wherein MMP7, MMP1, MMP-8 and at least two of IGFBP1, TNFRSF1A, TNFRSF1B, MMP2, MMP3, AGER, CXCL10, CCL11, CCL2, FAS, IL12B, IL1RA, S100A12, B2M, MPO, ICAM-1, TF, VWF, SPA, SPD, and MUC1 (KL-6), constitute at least 30 percent of the total markers in the panel.
12 . A kit for evaluating the progression of idiopathic pulmonary fibrosis in a subject, comprising a means for determining the plasma levels of a marker selected from the group consisting of MMP7, DEFA-1 DEFA-2, DEFA-3, S100A12, and IL12P40, wherein said kit does not contain means for determining the plasma levels of more than twenty other markers.
13 . A kit for diagnosing idiopathic pulmonary fibrosis comprising means for determining the plasma levels of a panel of markers comprising MMP7, MMP1, and MMP8 as well as either or both of IGFBP1 and TNFRSF1A, further comprising a positive control sample which, when reconstituted, comprises MMP7, MMP1, MMP8, IGFBP1 and/or TNFRSF1A at levels which are increased relative to normal plasma levels and optionally AGER at a level which is decreased relative to its normal plasma level.