Increased RP105-Negative B Cells in IgG4-Related Disease.

Four patients with IgG4-related disease (IgG4-RD) showed increased percentages of RP105-negative B cells in the peripheral blood. Case 1: A 66-year-old man having retroperitoneal fibrosis had 18.8% of RP105-negative B cells. Oral prednisolone improved the affected lesions and the percentage of RP105-negative B cells decreased (3.2%) after the treatment. Case 2: A 53-year-old man with retroperitoneal fibrosis had 27.9% of RP105-negative B cells. Case 3: A 38-year-old man with follicular hyperplasia showed increased percentage of RP105-negative B cells (8.3%). Case 4: A 60-year-old man with interstitial nephritis had 27.5% of RP105-negative B cells. The treatment decreased the numbers of RP105-negative B cells. Increased numbers of RP105-negatvie B cells is possibly associated with disease activity of IgG4-RD. Analysis of expression of RP105 on B cells may be helpful in evaluation of disease activity of IgG4-RD.

Relationship between inflammatory cells in bronchoalveolar lavage fluid and pathologic changes in the lung interstitium.

Bronchoalveolar lavage (BAL) is recognized as an important research tool for various lung diseases, but it is still uncertain whether inflammatory cells in BAL fluid (BALF) accurately reflect pathologic changes in the lung interstitium. We used a morphometric method to quantify the density of inflammatory cells in the lung interstitium by utilizing a computer-aided graphic analyzer and compared those findings with BALF results. Two types of animal models were studied, i.e., endotoxemia (Escherichia coli endotoxin) and hypersensitivity pneumonitis (inhaled ovalbumin). Male Wistar rats were used; the right lungs were lavaged and the left lungs were prepared for morphometric study. In the endotoxemia model, the neutrophil fraction in BALF and the neutrophil density in the lung interstitium correlated significantly at 18 h (r = 0.81, p < 0.05) and 24 h (r = 0.81, p < 0.05) but not at any other time points after injection. In the hypersensitivity pneumonitis model, the neutrophil fraction in BALF and the neutrophil density in the lung interstitium correlated significantly (r = 0.80, p < 0.05) only at 3 h after inhalation. The lymphocyte fraction in BALF and the lymphocyte density in the lung interstitium were correlated positively at 3 h (r = 0.83, p < 0.05), 1 day (r = 0.82, p < 0.05), 2 days (r = 0.67, p = NS), and 4 days (r = 0.87, p < 0.05), but not at 6 days after inhalation. Our data suggest that neutrophil fraction in BALF does not reflect neutrophil populations in the lung interstitium except at the time of maximal neutrophil count in lung lavage. For lymphocytes in the hypersensitivity pneumonitis model, those in BALF and in the lung interstitium roughly correlate in the majority of measurements.

Characterization of amiodarone pneumonitis as related to inflammatory cells and surfactant apoprotein.

STUDY OBJECTIVE: To characterize the inflammation observed in amiodarone-induced pneumonitis. DESIGN: The density of inflammatory cells in BAL fluid (BALF) and lung interstitium was quantified in a rat model of amiodarone pneumonitis. Immunoperoxidase staining for surfactant apoprotein was evaluated in lung tissue. ANIMALS AND INTERVENTIONS: Male Fischer 344 rats weighing 170 to 180 g received amiodarone, 150 mg/kg/d, suspended in 0.5% methylcellulose by gavage 5 d/wk. Control animals were given only methylcellulose. Rats were killed after 3, 5, 7, 9, and 12 weeks. Histologic sections were prepared for hematoxylin-eosin staining and the immunoperoxidase method. MEASUREMENTS AND RESULTS: Significant positive correlations between the density of neutrophils in BALF and the interstitium were seen at 5 weeks (r=0.90, p<0.05) and 7 weeks (r=0.90, p<0.05). Significant positive correlations were observed between the density of lymphocytes in BALF and the interstitium at 9 weeks (r=0.90, p<0.05) and 12 weeks (r=0.90, p<0.05). The density of type II pneumocytes was significantly increased in the amiodarone-fed rats. Extracellular surfactant apoprotein was found in the alveolar space and the cytoplasm of type II pneumocytes, Clara cells, and large, foamy macrophages throughout drug treatment. Extracellular surfactant apoprotein filled some alveoli at 9 weeks. CONCLUSIONS: The density of lymphocytes and neutrophils increased significantly in the BALF and the lung interstitium throughout amiodarone administration. The relationship between the density of lymphocytes in BALF and in the interstitium differed from that of neutrophils. In addition, amiodarone caused hyperplasia of type II pneumocytes and deposition of conglomerated, extracellular surfactant apoprotein in the alveolar space.