Activation of CD8+ T Cells in Chronic Obstructive Pulmonary Disease Lung.

Rationale: Despite the importance of inflammation in chronic obstructive pulmonary disease (COPD), the immune cell landscape in the lung tissue of patients with mild-moderate disease has not been well characterized at the single-cell and molecular level. Objectives: To define the immune cell landscape in lung tissue from patients with mild-moderate COPD at single-cell resolution. Methods: We performed single-cell transcriptomic, proteomic, and T-cell receptor repertoire analyses on lung tissue from patients with mild-moderate COPD (n = 5, Global Initiative for Chronic Obstructive Lung Disease I or II), emphysema without airflow obstruction (n = 5), end-stage COPD (n = 2), control (n = 6), or donors (n = 4). We validated in an independent patient cohort (N = 929) and integrated with the Hhip+/- murine model of COPD. Measurements and Main Results: Mild-moderate COPD lungs have increased abundance of two CD8+ T cell subpopulations: cytotoxic KLRG1+TIGIT+CX3CR1+ TEMRA (T effector memory CD45RA+) cells, and DNAM-1+CCR5+ T resident memory (TRM) cells. These CD8+ T cells interact with myeloid and alveolar type II cells via IFNG and have hyperexpanded T-cell receptor clonotypes. In an independent cohort, the CD8+KLRG1+ TEMRA cells are increased in mild-moderate COPD lung compared with control or end-stage COPD lung. Human CD8+KLRG1+ TEMRA cells are similar to CD8+ T cells driving inflammation in an aging-related murine model of COPD. Conclusions: CD8+ TEMRA cells are increased in mild-moderate COPD lung and may contribute to inflammation that precedes severe disease. Further study of these CD8+ T cells may have therapeutic implications for preventing severe COPD.

Idiopathic pulmonary hemosiderosis - A rare cause of chronic anemia.

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease marked by alveolar bleeding and accumulation of hemosiderin in the lungs. Here we present three cases of IPH. The first case is of a 26-year-old male with anemia, hemoptysis and dyspnea. Bronchoscopy confirmed diffuse alveolar hemorrhage (DAH). A diagnosis of IPH was made after ruling out other causes of DAH and observing good response to steroids. The patient's condition improved with prednisolone and azathioprine. The second case is of 26-year-old female with severe anemia. Imaging suggested IPH and lung biopsy confirmed it. She died shortly afterwards. The third case is of a 7-year-old male with chronic anemia. CT was suggestive of IPH and lung biopsy confirmed the diagnosis. Later, patient developed posterior reversible encephalopathy syndrome (PRES). This patient is stable on azathioprine and prednisolone. We aim to emphasize the importance of considering IPH as a differential in patients with DAH or chronic anemia.

Autosomal Recessive Agammaglobulinemia - first case with a novel TCF3 mutation from Pakistan.

Autosomal Recessive Agammaglobulinemia (ARA) is an uncommon type of primary immunodeficiency characterized by mutations in genes responsible for early B cell differentiation and function. One such gene is the TCF3 gene, which encodes a transcription factor important for immunoglobulin gene expression. We present the case of a 9 year old girl with history of diarrhea and recurrent pneumonias. Laboratory investigation showed significantly reduced levels of immunoglobulins along with a significant fall in the number of CD19+ cells. Genetic analysis identified a TCF3 gene base deletion covering exons 5-11.