Changes in Urinary Microbiome Populations Correlate in Kidney Transplants With Interstitial Fibrosis and Tubular Atrophy Documented in Early Surveillance Biopsies.

An unbalanced microbiome may lead to disease by creating aberrant immune responses. A recent association of cellular rejection with the development of interstitial fibrosis and tubular atrophy (IFTA) suggests the role of immune-mediated tissue injury. We hypothesized that developing IFTA correlates with altered urinary tract microbiomes (UMBs). UMBs at two serial time points, 1 and 6-8 months posttransplant, were assessed by 16S microbial ribosomal gene sequencing in 25 patients developing biopsy-proven IFTA compared to 23 transplant patients with normal biopsies and excellent function (TX) and 20 healthy nontransplant controls (HC). Streptococcus, the dominant genera in HC males, was lower in IFTA and TX males at 1 month compared to HCs. At 6-8 months, Streptococcus was further decreased in IFTA males, but normalized in TX. IFTA males and females had increases in number of genera per sample at 6-8 months. UMB composition varied substantially between individuals in all groups. Despite the wide variation in UMBs between individuals, IFTA was associated with a loss in dominant resident urinary microbes in males, and a parallel increase in nonresident, pathogenic bacteria in males and females. UMB changes may contribute to IFTA development by alteration of the host immune response.

Interstitial lung disorders in the indium workers of Korea: an update study for the relationship with biological exposure indices.

BACKGROUND: Korea is one of the highest indium-consuming countries worldwide. The present study aims to determine the relationship between interstitial lung disorders and indium exposure in Korea. METHODS: In 50 indium workers from seven plants, the effect of serum indium on the lungs was determined using laboratory tests, spirometry, and high-resolution computed tomography (HRCT). RESULTS: Higher serum indium and Krebs von den Lungen-6 (KL-6) levels were associated with HRCT-detected interstitial lung changes. Workers with high serum indium levels (≥3 µg/L) had longer exposure durations and a higher prevalence of HRCT-detected interstitial lung changes. KL-6 and surfactant protein-D (SP-D) levels were significantly higher in the highest serum indium quartile than the lowest quartile. Significant dose-effect relationships existed between serum indium levels and KL-6, SP-D levels and the prevalence of HRCT-detected interstitial lung changes. CONCLUSIONS: Workforce medical surveillance should be established to prevent indium-induced interstitial lung disease in Korea.

Cigarette smoking is associated with subclinical parenchymal lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA)-lung study.

RATIONALE: Cigarette smoking is a risk factor for diffuse parenchymal lung disease. Risk factors for subclinical parenchymal lung disease have not been described. OBJECTIVES: To determine if cigarette smoking is associated with subclinical parenchymal lung disease, as measured by spirometric restriction and regions of high attenuation on computed tomography (CT) imaging. METHODS: We examined 2,563 adults without airflow obstruction or clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis, a population-based cohort sampled from six communities in the United States. Cumulative and current cigarette smoking were assessed by pack-years and urine cotinine, respectively. Spirometric restriction was defined as a forced vital capacity less than the lower limit of normal. High attenuation areas on the lung fields of cardiac CT scans were defined as regions having an attenuation between -600 and -250 Hounsfield units, reflecting ground-glass and reticular abnormalities. Generalized additive models were used to adjust for age, gender, race/ethnicity, smoking status, anthropometrics, center, and CT scan parameters. MEASUREMENTS AND MAIN RESULTS: The prevalence of spirometric restriction was 10.0% (95% confidence interval [CI], 8.9-11.2%) and increased relatively by 8% (95% CI, 3-12%) for each 10 cigarette pack-years in multivariate analysis. The median volume of high attenuation areas was 119 cm(3) (interquartile range, 100-143 cm(3)). The volume of high attenuation areas increased by 1.6 cm(3) (95% CI, 0.9-2.4 cm(3)) for each 10 cigarette pack-years in multivariate analysis. CONCLUSIONS: Smoking may cause subclinical parenchymal lung disease detectable by spirometry and CT imaging, even among a generally healthy cohort.

Tissue targeting of anti-RNP autoimmunity: effects of T cells and myeloid dendritic cells in a murine model.

OBJECTIVE: To explore the role of immune cells in anti-RNP autoimmunity in a murine model of pneumonitis or glomerulonephritis, using adoptive transfer techniques. METHODS: Donor mice were immunized with 50 mug of U1-70-kd small nuclear RNP fusion protein and 50 mug of U1 RNA adjuvant. Whole splenocytes as well as CD4+ cell and dendritic cell (DC) subsets from the immunized mice were infused into naive syngeneic recipients. Anti-RNP and T cell responses were assessed by immunoblotting, enzyme-linked immunosorbent assay, and flow cytometry. Development of renal or lung disease was assessed by histology and urinalysis. RESULTS: Unfractionated splenocytes from donor mice without proteinuria induced predominantly lung disease in recipients (8 [57%] of 14 versus 2 [14%] of 14 developing renal disease; P = 0.046). However, infusion of CD4+ cells from donors without proteinuria induced renal disease more frequently than lung disease (7 [70%] of 10 versus 2 [20%] of 10; P = 0.01); adoptive transfer of RNP+CD4+ T cells from short-term culture yielded similar results (renal disease in 8 [73%] of 11 recipients versus lung disease in 3 [27%] of 11). Cotransfer of splenic myeloid DCs and CD4+ T cells from immunized donors prevented induction of renal disease in all 5 recipients (P = 0.026 versus recipients of fresh CD4+ cells alone), although lung disease was still observed in 1 of 5 mice. Transfer of myeloid DCs alone from immunized donors induced lung disease in 3 (60%) of 5 recipients, without evidence of nephritis. Cotransfer of splenocytes from mice with and those without nephritis led to renal disease in 4 of 5 recipients, without evidence of lung disease. CONCLUSION: These findings indicate that RNP+CD4+ T cells are sufficient to induce anti-RNP autoimmunity, tissue targeting in anti-RNP autoimmunity can be deviated to either a renal or pulmonary phenotype depending on the presence of accessory cells such as myeloid DCs, and DC subsets can play a role in both propagation of autoimmunity and end-organ targeting.

Analysis of the effect of surgical lung biopsy on serum KL-6 Levels in patients with interstitial pneumonia: surgical lung biopsy does not elevate serum KL-6 levels.

OBJECTIVE: It is well known that the serum level of KL-6 can be an indicator of disease activity in patients with interstitial pneumonia (IP). However, surgical lung biopsy is often required for the diagnosis of IP, although this can result in IP exacerbation. METHODS: The effect of surgical lung biopsy on the serum level of KL-6 in patients with IP was analyzed. Thirty-two cases of IP were examined in this study. There were no cases showing exacerbation of IP. RESULTS: The serum level of KL-6 demonstrated 1067+/-550 U/ml (mean+/-SD) before lung biopsy, 991+/-471 U/ml a day, 824+/-377 U/ml 4 days and 826+/-384 U/ml 7 days after lung biopsy. The serum KL-6 levels on the 1st, 4th, 7th day after the lung biopsy were significantly lower than that before the lung biopsy (P<0.05, P<0.01 and P<0.01, respectively). The percent decrease of the serum KL-6 levels on the 4th day (the lowest level) was dependent on the urine volume, and the analysis of the urinary levels of KL-6 showed a transient increase in urinary KL-6 excretion, suggesting that the decrease in serum KL-6 levels associated with surgical lung biopsy may be caused by this increase in urinary KL-6 excretion. CONCLUSION: Surgical lung biopsy of patients with IP has little effect on the increase in serum KL-6 levels. An elevation of serum KL-6 after surgical lung biopsy may indicate exacerbation of IP.

Endothelin-1 excretion in urine in active pulmonary sarcoidosis and in other interstitial lung diseases.

Endothelin-1 (ET-1) is a vasoactive, mitogenic peptide that is variably increased in Bronchoalveolar Lavage Fluid (BALF) and immunohistochemically found in lung tissue of patients with Interstitial Lung Disease (ILD). To assess if endogenous ET-1 production is increased in ILD we evaluated 24 hour (24h) urine excretion of ET-1 in 20 patients with ILD and 10 healthy age-matched controls (HC). Eight patients with active pulmonary sarcoidosis (S), 6 with idiopathic pulmonary fibrosis (IPF) and 6 with focal lung fibrosis due to inactive pulmonary tuberculosis (hTB) were studied. Plasma ET-1 levels (ET-1pl, pg/ml) and 24h ET-1 levels in urine (ET-1ur, ng/24h) were measured by a specific radio-immunoassay. Determinations of ET-1p1 and ET-1ur were repeated in S and IPF patients after 30 days of prednisone (0.75 mg/kg/day) treatment. ET-1p1 concentrations were not different between HC (5.34 +/- 0.48), S (5.95 +/- 0.96), IPF (4.75 +/- 1.37) and hTB (5.97 +/- 1.05) groups. ET-1ur was significantly higher in S (189.50 +/- 60.57) than in HC (69.00 +/- 10.76), IPF (62.17 +/- 19.07) and hTB (82.00 +/- 24.97). After prednisone, ET-1ur in the S group decreased significantly (189.50 +/- 60.57 to 94.00 +/- 13.60), and the decrease paralleled the improved clinical status. In S patients, ET-1ur was not significantly correlated to the degree of respiratory impairment, but it was significantly correlated to the intensity of lymphocytic alveolitis (r = 0.80).(ABSTRACT TRUNCATED AT 250 WORDS)