title: The role of microvascular injury in the evolution of idiopathic pulmonary fibrosis.
abstract: Interstitial lung disease compatible with idiopathic pulmonary fibrosis (IPF) developed in 19 previously healthy patients. Although interstitial and/or honeycomb parenchymal fibrosis was present in all, there were patchy areas of paucicellular septal capillary injury along with corroborative direct immunofluorescent evidence of a humorally mediated microvascular injury syndrome. Significantly elevated factor VIII levels were seen in 17 of 18 patients tested. Antiphospholipids were present in all 18 patients tested, comprising antibodies of phosphatidylethanolamine, beta-2 glycoprotein, phosphatidylcholine, and/or phosphatidylserine. Anti-Ro and/or anti-ribonucleoprotein (RNP) antibodies were seen in 4 patients. Serologic evidence of infection with cytomegalovirus (CMV) was found in 9 patients and parvovirus B19 (B19) in 9 patients; 1 patient was not tested. Molecular studies revealed B19 DNA in 6 of 6 B19-seropositive patients. In situ hybridization studies revealed CMV RNA in pulmonary cells in patients with serologic evidence of active CMV infection despite the absence of cytopathic changes typical of CMV infection. Antiphospholipid antibodies, antiendothelial cell antibodies, and/or endotheliotropic viral infections related to B19 and CMV may be of pathogenetic importance to the evolution of IPF. This report underscores the potential importance of microvascular injury in the evolution of IPF.
authors.affiliation: Department of Pathology, Ohio State University, N816 Doan Hall, 410 W 10th Ave, Columbus, OH 43210, USA.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Magro
authors.forename: James
authors.initials: J
authors.lastname: Allen
authors.forename: Amy
authors.initials: A
authors.lastname: Pope-Harman
authors.forename: W James
authors.initials: WJ
authors.lastname: Waldman
authors.forename: Patrick
authors.initials: P
authors.lastname: Moh
authors.forename: Susan
authors.initials: S
authors.lastname: Rothrauff
authors.forename: Patrick
authors.initials: P
authors.lastname: Ross
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000276:immunology; D017152:Antibodies, Antiphospholipid / Q000097:blood; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000150:complications / Q000473:pathology; D004279:DNA, Viral / Q000032:analysis; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005169:Factor VIII / Q000032:analysis; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D017403:In Situ Hybridization; D008168:Lung / Q000098:blood supply / Q000473:pathology*; D008297:Male; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D010322:Parvoviridae Infections / Q000150:complications / Q000473:pathology; D016732:Parvovirus B19, Human / Q000235:genetics / Q000302:isolation & purification; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000473:pathology* / Q000821:virology; D012367:RNA, Viral / Q000032:analysis; D012261:Ribonucleoproteins / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D017152:Antibodies, Antiphospholipid; D004279:DNA, Viral; D012367:RNA, Viral; D012261:Ribonucleoproteins; C035356:SS-A antibodies; D005169:Factor VIII