Antibodies to collagen in patients with idiopathic pulmonary fibrosis.
STUDY OBJECTIVE: The pathogenesis of idiopathic pulmonary fibrosis (IPF) is uncertain. This investigation was undertaken to determine if antibodies to human native collagens and their chains are present in the serum of the patients with IPF and to examine their relationship with clinical factors. MATERIALS: Serum specimens were obtained from 45 subjects. The subjects were separated into three distinct groups: group 1 consisted of 16 patients with IPF; group 2a, 9 patients with pulmonary fibrotic scars from previous tuberculosis were examined as a control group; group 2b, 20 normal individuals matched by age and sex. The collagen antigens used in this study consisted of four genetically distinct types, I, II, III, IV and their corresponding chains alpha 1(I) + alpha 2(I), alpha 1(II), and alpha 1(III). METHODS: a passive microhemagglutination assay was used to test the antibody activity in the sera of both patients and controls. Titration was performed in microtiter plastic plates, using 0.5 percent cell suspension. The specificity of anticollagen antibodies was then tested using an absorption serum technique with native collagens and their chains. Hemagglutination enhancement and inhibition tests, as well as chromatography, were used to determine the type of antibodies. RESULTS: Thirteen of 16 (81 percent) patients with IPF (group 1) had antibodies against at least one type of native collagen or one type of collagen chain in titers up to 1:512. Twelve patients exhibited anticollagen antibodies with titers above 1:16. By contrast, only 2 of 9 (22 percent) subjects with fibrotic scars (group 2a) and 3 of 20 (15 percent) normal subjects (group 2b) had antibody activity in titers up to 1:8. The differences between group 1 and group 2a and 2b were statistically significant, (p < 0.05 and p < 0.001, respectively). There was an inverse, statistically significant correlation between duration of the disease (IPF) and antibody activity. The correlation coefficient between duration of the disease and titers of antibodies to type III collagen (native and/or chain) was higher than the correlation coefficient between duration of the disease and titers to collagen I. The enhancement and inhibition of agglutination tests, as well as the chromatography, showed that the agglutination factors were antibodies of IgG and IgM classes. The antibody absorption test revealed that the anticollagen antibodies were specific for each collagen and its chain and there was no cross-reaction. CONCLUSION: This study suggests that the anticollagen antibodies could be a marker of IPF activity and may perpetuate the lung tissue inflammation. It is still unclear if the autoimmunity of the collagen participates in the pathogenesis of IPF or the presence of the anticollagen antibodies is simply an epiphenomenon.