The examination of serum samples from coalminers for the presence of auto antibodies that might be involved in the development of progressive massive fibrosis. Final report on CEC Contract 6244-00/8/104

1. The possibility that the development of pneumoconiosis is associated with an autoimmune reaction was explored by the examination of serum samples from coalminers in all the geographical areas of the BritishNational Coal Board.2. Lists of men asked to donate a blood sample were prepared to include equal numbers of men in each radiographic category as far as possible.However, there were few men available with category 3 simple pneumoconiosis and very few younger men with progressive massive fibrosis.3. At the time of blood collection a questionnaire was completed foreach man to obtain information on his general health, smoking habits and working history.4. A total of 2,455 serum samples was collected from coalminers and the number of samples from each mining area reflected the distribution of the workforce of the National Coal Board throughout Britain.Of this total there were 712 men with no radiological evidence of pneumoconiosis, 563 with category 1, 668 with category 2, 58 with category 3 simple pneumoconiosis, 420 with progressive massive fibrosis and a further 34 with no recent radiographic reading available. In addition, serum samples were obtained from blood donors with the co-operation of the National Blood Transfusion Service, 175 from Edinburgh and 85 from Cardiff. These samples were required mainly to act as baseline controls for the test systems employed in the study.5. Sera from both the controls and the coalminers were tested for the presence of antinuclear factor, rheumatoid factor, and antibodiesto connective tissue compoments such as reticulin. Where anti-nuclear factor antibodies were detected their immuno globulin type was determined.6. The presence of antinuclear factor in both coalminers and controls appeared to be largely dependent on age. An apparent weak association between antinuclear factor and the presence ofpneumoconiosis disappeared when cases were grouped into equalage brackets. 7. The predominant type of immunoglobulin in sera containing anti-nuclear factor was IgM in both coalminers and controls (56% and 57% respectively). In the controls all antibodies showing a “”speckled”” staining pattern were IgM. In young miners this was also true but an increase in the proportion of IgG antibodies was evident with increase in disease in the older groups. Most antibodies giving a “”chromatin”” staining pattern were IgM although the proportion of IgG sera increased with simple pneumoconiosis category in the older group of coalminers. Antibodies giving a “”nucleolar”” staining pattern were mainly IgG although the proportion of IgM sera increased with radiographic category in the older coalminers. Where both rheumatoid factor and antinuclear factor were present, the antinuclear factor staining pattern was mainly of the “”speckled”” or the “”chromatin”” type.8. Only two categories had rheumatoid factor at frequencies different from that expected within the- normal population. The older category 0 men had less than expected while a rising percentage with increasing lesion size was evident in the progressive massive fibrosis group. These differences in rheumatoid factor gave a highly significant association with pneumoconiosis category (X2 4 = 22.35, P < 0.0005, assuming independence of the tests). However, when men believed to have rheumatoid arthritis were excluded, this association was not statistically significant (X2 5 = 11.99, P < 0.05).9. There was no association between the occurrence of ""reticulin"" antibodies and the presence of pneumoconiosis.10. Men who had shown progression of their radiographic category during the five year period prior to blood collection showed little difference in the frequency of circulating antinuclear factor and rheumatoid factor when compared to miners who had not progressed.11. For antinuclear factor and anti-reticulin antibodies there""were""no differences between (a) men who had worked on the coal face forat least ten years, (b) men who had only worked on the surface, and (c) all other miners. Surface workers appeared to have less rheumatoid factor than underground workers but the differences werenot statistically significant.12. Heavy smokers (> 210 cigarettes per week) regardless of their radiographic category appeared to have higher levels of circulating autoimmune factors than men who smoked less. Initially there appeared to be an association of antinuclear factor with radiographic into narrow age brackets this association was found to be age-related.13. The frequencies of circulating antinuclear factor and rheumatoid factor appeared to be higher in coalminers from South Wales than in men from the Midlands of England or the North East of England and Scotland. However, this applied mainly to cases with progressive massive fibrosis and men with no pneumoconiosis although in this study relatively few of the latter were from South Wales. The difference in antinuclear factor frequency between the areas was apparent even within the same age brackets and thus may representa geographical difference either in the men themselves or in the conditions in which they work.14. In conclusion, this study has produced little evidence that.the development of pneumoconiosis is related to the appearance of the circulating autoimmune factors,””antinuclear factor, rheumatoid factor or “”reticulin”” antibodies. If there is an autoimmune phenomenon involved in the pathogenesis of this disease it must depend on other immunological factors and future studies will include tests for the presence of antibodies to lung tissues and the reactivity of T and B lymphocytes. “”

Publication Number: TM/79/12

First Author: Boyd JE

Other Authors: Robertson MD , Davis JMG

Publisher: Edinburgh: Institute of Occupational Medicine

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