Circulating thymic hormone activity in patients with primary and secondary immunodeficiency diseases

Levels of circulating thymic hormone, facteur thymique serique (FTS), were quantitated in the serum of normal subjects ranging in age from three days to 85 years and in a wide variety of patients with primary and secondary immunodeficiency diseases. FTS levels were low in the serum of a high proportion of patients with common variable immunodeficiency and selective absence or deficiency of IgA. Patients with DiGeorge syndrome always had low levels. In infants with severe combined immunodeficiency (SCID) FTS levels were low in 21 of 23 instances and normal in only two. In patients classified as having primary T-cell deficiency FTS levels were regularly lower than normal as in those with osteopetrosis and ataxia telangiectasia. In patients with Wiskott-Aldrich syndrome and chronic mucocutaneous candidiasis FTS levels were frequently lower than normal. In patients with systemic lupus erythematosus (SLE) FTS levels were below the normal range in the majority of instances, whereas FTS levels within the normal range were characteristic of patients with the X-linked infantile form of agammaglobulinemia (Bruton's disease) and patients with progeria. Serums from seven patients were shown to inhibit FTS activity. Of these, serum from six patients with common variable immunodeficiency was studied for its capacity to inhibit synthetic FTS and FTS activity in normal serum. In two of these, FTS activity was inhibited in normal serum, and in five synthetic FTS activity was inhibited. Another patient with immunodeficiency, who had increased IgM levels and neutropenia, also had a serum inhibitor that was active against FTS. Search for an inhibitor of FTS in the serum of individual patients with SCID, chronic mucocutaneous candidiasis and a thymectomized infant revealed no such inhibition. Twenty-seven patients with common variable immunodeficiency were studied for both FTS activity and lymphocytic proliferative responses to phytomitogens and antigens. In 10 of these patients, FTS levels were low and in three of these 10 the responses to both mitogens and antigens were deficient; in four, responses were normal for both, and in three, the responses to antigen were low but the responses to mitogen were normal. In four of 27 patients with low FTS titers, however, an inhibitor against FTS activity was present in their serum, but their proliferative response to mitogens was normal and in two responses to antigens were reduced as well. This finding may explain the frequent dissociation of FTS activity and lymphocyte functions.