The pulmonary involvement in disorders of immune or inflammatory regulation can range from a primary manifestation such as with sarcoidosis or a relatively minor manifestations such as seen with the Mendelian Susceptibility to Mycobacterial Disease immune deficiencies. While both of these can be associated with granulomatous inflammation in the lung, the clinical pulmonary manifestations are quite different as are the management strategies. The Pulmonary Clinical Medicine Section (PCMS) has sought to capitalize on the close collaboration with the Laboratory of Clinical Infectious Diseases and other branches within the NIAID and NIAMS focused on these disorders to describe the pulmonary manifestations of known and emerging immune and inflammatory diseases. Over the past year we have completed characterization of the lung manifestations seen in Autoimmune Lymphoproliferative Syndrome (ALPS) and compared and contrasted these to similar presentations seen in newly described diseases which may have previously been categorized as ALPS or Common Variable Immune Deficiency (CVID). These include disease associated with mutations in CTLA4, PI3K, and LRBA. The PCMS has been actively involved in characterizing the protean lung manifestations of GATA Binding Protein 2 (GATA2) deficiency have provided unique insight into the role of alveolar macrophage dysfunction in development of pulmonary alveolar proteinosis and intracellular control of mycobacteria and fungi in the lung. Lung manifestations associated with Mycobacterium kansasii presenting with significant mediastinal adenopathy were recently reported. The first comprehensive report of a prospectively evaluated cohort of patients with Autoimmune Polyendocrinopathy, Candidiasis, and Ectodermal Dystrophy (APECED) Syndrome was recently published. This included detailed description of the unique pulmonary manifestations of disease aided by obtaining bronchial and alveolar specimens for research under the NHLBI Research Respiratory Tract Procedures protocol (07-H-0142). Recent collaboration with investigators at the University of North Carolina seeks to better define the role of STAT3 in altered airway clearance. We recently published a review of lung disease associated with STAT3 mutated hyper IgE syndrome and compared that to lung manifestations of other hyper IgE syndromes. Preliminary data suggest that STAT3 through IL6 signaling may have a significant role in repair mechanisms in the airways.
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