Detection of anti-cytokeratin 8 antibody in the serum of patients with cryptogenic fibrosing alveolitis and pulmonary fibrosis associated with collagen vascular disorders.
BACKGROUND: It has been suggested that the humoral immune system plays a role in the pathogenesis of cryptogenic fibrosing alveolitis (CFA). Although circulating autoantibodies to lung protein(s) have been suggested, none of the lung proteins have been characterised. The purpose of this study was to determine the antigen to which the serum from patients with pulmonary fibrosis reacted. METHODS: The anti-A549 cell antibody was characterised in a patient with CFA using Western immunoblotting and immunohistochemical staining of A549 cells. As we identified that one of the antibodies against A549 cells was anti-cytokeratin 8, the expression of mRNA of cytokeratin 8 in A549 cells was evaluated. In addition, we attempted to establish an enzyme linked immunosorbent assay to measure the levels of anti-cytokeratin 8 antibody in the serum of patients with CFA and pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). RESULTS: Initially two anti-A549 cell antibodies were detected in the serum of patients with pulmonary fibrosis, one of which was characterised as anticytokeratin 8 antibody by Western immunoblotting. We were able to establish an ELISA to measure anti-cytokeratin 8 antibody and found significantly higher levels in patients with CFA and PF-CVD than in normal volunteers, patients with sarcoidosis, pneumonia, and pulmonary emphysema. CONCLUSIONS: One of the anti-A549 cell antibodies in the serum of patients with CFA was against cytokeratin 8. The serum levels of anti-cytokeratin 8 antibody were increased in patients with CFA and PF-CVD. These results suggest that anticytokeratin 8 antibody may be involved in the process of lung injury in pulmonary fibrosis. (+info)
Collagenous gastritis and collagenous colitis: a report with sequential histological and ultrastructural findings.
The case is reported of a young adult man with collagenous gastritis, an extremely rare disorder with only three case reports in the English literature, who subsequently presented with collagenous colitis. Sequential gastric biopsies showed a notable increase in thickness of the subepithelial collagen band. Ultrastructural study of gastric and rectal mucosa showed the characteristic subepithelial band composed of haphazardly arranged collagen fibres, prominent degranulating eosinophils, and activated pericryptal fibroblasts. (+info)
Elevated serum and BAL cytokeratin 19 fragment in pulmonary fibrosis and acute interstitial pneumonia.
Cytokeratin 19 fragment (CK19) levels in serum have already been documented as a useful tumour marker for lung cancer. In the present study, it was hypothesized that CK19 may be increased in the serum and epithelial lining fluid of the respiratory tract from patients with pulmonary fibrosis. CK19 was measured in the serum and bronchoalveolar lavage fluid (BALF) of patients with pulmonary fibrosis and the correlation between CK19 levels and clinical parameters evaluated. Nineteen patients diagnosed with idiopathic pulmonary fibrosis (IPF), eight with pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD), seven patients with acute interstitial pneumonia (AIP), and 10 normal smokers as a control group were studied. CK19 levels in sera of patients with IPF and patients with PF-CVD were significantly increased compared to those of normal smokers. CK19 levels in sera of patients with AIP were significantly increased compared to those of other groups. CK19 values in the BALF of patients with pulmonary fibrosis were significantly elevated compared to those of normal smokers. CK19 values in sera charged according to the progression or improvement of the acute lung injury. Immunohistochemical study using pulmonary tissues obtained from patients with AIP demonstrated that the hyaline membrane and proliferating type II pneumocytes were stained by anti-human cytokeratin 19 antibody. These data demonstrated that the measurement of cytokeratin 19 fragment is a useful parameter to evaluate the activity of lung epithelial cell damage and repair. (+info)
Collagen dysplasia (cutaneous asthenia) in a cat.
Hereditary collagen dysplasias comprise a complex group of connective-tissue disorders that result in the reduced tensile strength of affected tissues. These processes are called cutaneous asthenia in the skin of dogs and cats. We report here the case of a crossbred male cat, aged 6 months, that presented with two skin wounds in the region of the right thorax and right iliac tuberosity. The skin of these regions and of the animal's dorsum was hyperextensible, smooth to the touch, and easily torn with minor trauma. Microscopic examination of skin samples revealed reduced dermal connective tissue consisting of shortened and fragmented collagen fibers. Normal fibers were intermingled with altered fibers. Ultrastructural changes in collagen fibers included disorientation of fibrils within the same bundle, marked spacing differences, and variation in the diameter of transverse sections. The fibrils maintained the transverse striations characteristic of normal collagen. (+info)
Report of five novel and one recurrent COL2A1 mutations with analysis of genotype-phenotype correlation in patients with a lethal type II collagen disorder.
Achondrogenesis II-hypochondrogenesis and severe spondyloepiphyseal dysplasia congenita (SEDC) are lethal forms of dwarfism caused by dominant mutations in the type II collagen gene (COL2A1). To identify the underlying defect in seven cases with this group of conditions, we used the combined strategy of cartilage protein analysis and COL2A1 mutation analysis. Overmodified type II collagen and the presence of type I collagen was found in the cartilage matrix of all seven cases. Five patients were heterozygous for a nucleotide change that predicted a glycine substitution in the triple helical domain (G313S, G517V, G571A, G910C, G943S). In all five cases, analysis of cartilage type II collagen suggested incorporation of the abnormal alpha1(II) chain in the extracellular collagen trimers. The G943S mutation has been reported previously in another unrelated patient with a strikingly similar phenotype, illustrating the possible specific effect of the mutation. The radiographically less severely affected patient was heterozygous for a 4 bp deletion in the splice donor site of intron 35, likely to result in aberrant splicing. One case was shown to be heterozygous for a single nucleotide change predicted to result in a T1191N substitution in the carboxy-propeptide of the proalpha1(II) collagen chain. Study of the clinical, radiographic, and morphological features of the seven cases supports evidence for a phenotypic continuum between achondrogenesis II-hypochondrogenesis and lethal SEDC and suggests a relationship between the amount of type I collagen in the cartilage and the severity of the phenotype. (+info)
Clinical evaluation of idiopathic interstitial pneumonia and interstitial pneumonia associated with collagen vascular disease using logistic regression analysis.
OBJECTIVE: To clarify the differences in the clinical features between idiopathic interstitial pneumonia (IIP) and interstitial pneumonia associated with collagen vascular diseases (CVD-IP). METHODS: Symptoms, radiographic findings, pulmonary function, blood chemistry data including autoantibody, and bronchoalveolar lavage fluid (BALF) findings were compared using multiple logistic regression analysis. PATIENTS: The subjects were 44 patients clinically diagnosed with IIP and 33 patients with CVD-IP. RESULTS: The clinical features related to IIP were as follows: male sex, advanced age, past history of hypertension, presence of cough, exertional dyspnea, digital clubbing, an increased level of gamma-globulin, decreased lung volume on chest X-ray, and typical type according to the criteria for IIP on chest X-ray. Increased levels of rheumatoid factor and total cell number in BALF were related to CVD-IP. CONCLUSION: These findings are considered to be useful to differentiate IIP and CVD-IP. (+info)
Role of carbohydrate antigens sialyl Lewis (a) (CA19-9) in bronchoalveolar lavage in patients with pulmonary fibrosis.
BACKGROUND: It has been reported that carbohydrate antigen sialyl Lewis (a) (CA19-9) levels are elevated in serum as well as in bronchoalveolar lavage fluid (BALF) of patients with pulmonary fibrosis. However, the biological significance of CA19-9 is unclear. OBJECTIVE: The purpose of the present study was to evaluate correlations between CA19-9 levels in BALF and several biochemical as well as clinical parameters in patients with pulmonary fibrosis. In addition, biological functions of CA19-9 were also examined. METHODS: We studied 24 patients with a diagnosis of pulmonary fibrosis: 16 with idiopathic pulmonary fibrosis (IPF) and 8 with pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD). In BALF, carbohydrate antigens sialyl Lewis (a) (CA19-9), elastase: alpha(1)-proteinase inhibitor complex (E-PI), hepatocyte growth factor (HGF), LDH, IgG, IgA, albumin, and cell differentiation were measured. We also evaluated the effects of CA19-9 on neutrophil functions. RESULTS: CA19-9/albumin levels in BALF significantly correlated with HGF/albumin, elastase/albumin, LDH/albumin, total number of alveolar macrophages, and total number of neutrophils. Purified CA19-9 had a chemotactic activity for neutrophils. In addition, neutrophil chemotactic activity to C5a, fMLP, and interleukin 8 was significantly stimulated after incubation with purified CA19-9. Furthermore, CA19-9 increased the expression of CD15s on neutrophils. CONCLUSIONS: Our data demonstrated (i) CA19-9 in BALF correlated with other markers of inflammation in pulmonary fibrosis, and (ii) CA19-9 can modify neutrophil functions. These results suggest that CA19-9 may play a role in the process of lung injury in patients with pulmonary fibrosis. (+info)
Alternate-day prednisone therapy and human lymphocyte subpopulations.
The mechanisms and kinetics of the immunosuppressive effects of alternate-day prednisone were investigated in a group of patients with a variety of inflammatory diseases receiving a range of alternate-day prednisone doses from 5 to 120 mg. Total circulating lymphocyte and monocyte counts, as well as proportions of lymphocyte subpopulations defined both by surface markers and by in vitro functional capacities, were studied. At 8 a. m. of the day on prednisone, just before drug administration, lymphocyte and monocyte counts, proportions of lymphocyte subpopulations, as well as in vitro lymphocyte blastogenic responses to various mitogenic and antigenic stimuli were normal. 4 h after the administration of prednisone, there was a profound lymphocytopenia and monocytopenia, with a differential depletion of thymus-derived lymphocytes as well as various functionally defined lymphocyte subpopulations. Lymphocyte kinetic studies using a radioactive chromium-labeled autologous lymphocytes showed that the lymphocytopenia was due predominantly to a transient depletion of the recirculating portion of the intravascular lymphocytepool. All these parameters returned to normal by 8 a.m. of the following day (off prednisone) and remained normal throughout the day. This very transient lymphocytopenia and monocytopenia after prednisone, with normal cell numbers, proportions, and functions throughout the remainder of the 2-day cycle, was associated with suppression of disease activity, yet did not affect cutaneous delayed hypersensitivity in these patients nor increase the likelihood of infectious complications. This drug-associated cyclic and transient monocytopenia and selective lymphocytopenia is best explained by a redistribution of recirculating lymphocytes to other body compartments, particularly the bone marrow. (+info)