Consistent with the hypothesis that pulmonary epithelial apoptosis is the key to the acute exacerbation of idiopathic pulmonary fibrosis (IPF), we conducted serological identification of Ags by recombinant expression cloning (SEREX) analysis using type II alveolar cell carcinoma (A549) cell lines to identify disease-related Abs. In a survey of Abs to the recombinant autoantigens identified by SEREX analysis, five Abs were identified as novel candidates for the acute exacerbation of IPF. Abs to annexin 1 were detected in 47 and 53% of the sera and bronchoalveolar lavage materials from patients with acute exacerbation of IPF. Some identical TCR Vβ genes were identified in sequential materials obtained at 1–3 mo in all 10 acute exacerbation IPF cases, suggesting that some infiltrating CD4-positive T cells sharing limited epitopes expand by Ag-driven stimulation during disease extension. The CDR3 region of these identical TCR Vβ genes showed high homology with the N-terminal portion of annexin 1, including in the HLA-DR ligand epitopes predicted by TEPITOPE analysis. By Western blotting analysis and observation of the CD4-positive T cell responses in bronchoalveolar lavage samples, the N-terminal portion of annexin 1 was cleaved and found to induce marked proliferative responses of CD4-positive T cells in three patients. Our study demonstrates that annexin 1 is an autoantigen that raises both Ab production and T cell response in patients with acute exacerbation of IPF, and that the N-terminal portion of annexin 1 plays some role in the pathogenesis of acute exacerbation in IPF patients.
The concentrations of elements in urine obtained from cats with urolithiasis were compared with those of healthy cats. The concentration of several elements, such as sodium (Na), phosphorus (P), sulfur (S), and potassium (K), in urine obtained from cats with urolithiasis was significantly higher than that of healthy cats. A significant correlation (p<0.01) was found between the concentration of magnesium (Mg) and that of other elements, such as P (r=0.8913), S (r=0.6817), and K (r=0.8391), in the urine obtained from healthy cats. A significant correlation (r=0.7422, p<0.05) was also obtained between the concentration of K and that of P in urine collected from cats with urolithiasis, but the slope of regression line was significantly different from that of the urine obtained from healthy cats. Other correlations observed in healthy cats were not obtained from cats with urolithiasis. However, a significant correlation between the concentration of magnesium (Mg) and that of calcium was obtained only from cats with urolithiasis. The results of the present study suggest that urinary concentrations of various elements in cats with urolithiasis are higher than those of healthy cats. Furthermore, the balance of elements in the urine of cats with urolithiasis was altered.
We examined the immunoglobulin heavy chain variable (Ig VH) region genes of 11 low-grade pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas by a two-step polymerase chain reaction (PCR) and sequencing analysis. We observed frequent somatic mutations with the positive selective pressure of the rearranged Ig VH genes in all cases, indicative of postgerminal center cell origin. Eight cases demonstrated intraclonal variations (hypermutation with intraclonal variation type), but the other cases showed only one major clone without intraclonal heterogeneity (hypermutation without intraclonal variation type). The former might reflect the reentry of marginal zone B cells into a germinal center environment leading to further mutations. The latter might be no longer susceptible to hypermutation mechanisms and seemed to be stable. Four cases used Ig VH genes (hv3019b9, VH26, and VH4.21), which are frequently found in a variety of autoantibodies, such as cold agglutinins, rheumatoid factors, and anti-DNA antibodies.
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