Serum Protein Changes in Caplan's Syndrome

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Abstract
The British literature on Caplan''s syndrome is briefly reviewed, with particular reference to the pathogenesis of the pulmonary lesions, and an investigation is described which was designed to throw fresh light upon this problem. Statistical analysis of the results revealed an association between the levels of several serum protein fractions and the severity of the lung lesions independently of the severity of the arthritis. Elevation of [alpha]2- and gamma-globulin and reduction of albumin and of the albumin/[alpha]2-globulin ratio are consistent with the tuberculous theory of the etiology of these lesions, but a tend was also observed towards higher levels of [beta]-globulin with increasing severity of pulmonary lesions. Rheumatoid arthritis itself rarely produces this effect and no increase of [beta]-globulin has been reported in tuberculosis. The previously observed association between the presence of "Caplan lesions" in the lungs and positive hemagglutination tests for rheumatoid arthritis was confirmed, a significant correlation was demonstrated between the sheep cell agglutination titer and the [beta]-globulin level. The literature on the nature of the rheumatoid factor is reviewed and the conclusion reached that R. F. exists naturally as a 19S macroglobulin migrating electrophoretically as a [beta]2-globulin, but that transformation to a 22S gamma-globulin occurs when serum is stored in the liquid state. Based on this conclusion and on the three-fold relationship observed between the severity of "Caplan lesions", the hemagglutination titer, and the [beta]-globulin level, a hypothesis is proposed that the nodular lesions described by Caplan, and perhaps some other lesions associated with rheumatoid arthritis such as subcutaneous necrobiotic nodules, may be sites of synthesis of the rheumatoid factor. It is further suggested that the raw material for this synthesis may consist of [beta]-glycoprotein derived from the ground-substance of degenerating collagenous tissue.