We aimed to identify peripheral blood mononuclear cell (PBMC) gene expression profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) by performing microarray experiments of PBMCs in discovery and replication cohorts of IPF patients. Microarray analyses identified 52 genes associated with transplant-free survival (TFS) in the discovery cohort. Clustering the microarray samples of the replication cohort using the 52-gene outcome-predictive signature distinguished two patient groups with significant differences in TFS. We studied the pathways associated with TFS in each independent microarray cohort and identified decreased expression of “The costimulatory signal during T cell activation” Biocarta pathway and, in particular, the genes CD28, ICOS, LCK, and ITK, results confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A proportional hazards model, including the qRT-PCR expression of CD28, ICOS, LCK, and ITK along with patient’s age, gender, and percent predicted forced vital capacity (FVC%), demonstrated an area under the receiver operating characteristic curve of 78.5% at 2.4 months for death and lung transplant prediction in the replication cohort. To evaluate the potential cellular source of CD28, ICOS, LCK, and ITK expression, we analyzed and found significant correlation of these genes with the PBMC percentage of CD4+CD28+ T cells in the replication cohort. Our results suggest that CD28, ICOS, LCK, and ITK are potential outcome biomarkers in IPF and should be further evaluated for patient prioritization for lung transplantation and stratification in drug studies.

In recipients of allogeneic bone marrow, asymptomatic CMV infection of the lung is a major risk factor for subsequent CMV interstitial pneumonia. Prophylactic ganciclovir is effective in preventing the development of CMV interstitial pneumonia in patients with asymptomatic infection.

IgG autoantibodies with avidity for pulmonary epithelium, and the potential to mediate cytotoxicity, are prevalent in patients with COPD. Autoreactive adaptive immune responses may be important in the etiology of this disease.

Patients with IPF with anti-HSP70 autoantibodies have more near-term lung function deterioration and mortality. These findings suggest antigen-specific immunoassays could provide useful clinical information in individual patients with IPF and may have implications for understanding IPF progression.

Bronchiolitis obliterans syndrome (BOS) is a progressive, insidious, and often fatal lung allo-reaction that can occur following allogeneic hematopoietic stem cell transplantation (HCT) or allogeneic lung transplantation. Current estimates in the literature suggest that approximately 2–3% of all allogeneic HCT recipients and 6% of patients who develop chronic GVHD will develop this syndrome. However, based on newer data it is likely that the true incidence of BOS is higher. Unfortunately, the survival and treatment of patients with BOS after HCT has not improved over the last 20 years. Attempts at clinical trials have been hindered by the lack of uniform diagnostic criteria and inability to detect the syndrome at a reversible stage in its natural history. Recently, the NIH consensus project for criteria in chronic GVHD has made recommendations regarding the diagnosis of BOS and monitoring of lung disease among long term survivors. Although a rare and poorly understood manifestation of chronic GVHD, BOS occurs commonly after lung transplantation and is similar in pathology, clinical presentation, radiographic presentation, and presumed immunologic pathogenesis. This review describes the current understanding of the epidemiology and pathogenesis of BOS and presents information on evaluations and therapies for patients with BOS after HCT.