Immunologic and clinical correlates of bronchial challenge responses to Bermuda grass pollen extracts.

We have studied 26 patients with asthma who had positive skin tests for Bermuda grass pollen antigen (BGP) with history, immunologic assays, and bronchial challenge with BGP. In these patients IgE anti-BGP RAST titers were higher in those with positive, 6.8 +/- 4.4% (mean +/- SEM) compared to those with negative bronchial challenges, 2.7 +/- 0.4% (p less than 0.02). Historical data did not predict bronchial challenge response. IgG4 anti-BGP RAST was not different in patients with positive and negative challenges but was markedly increased, 15.3 +/- 11.9%, in patients who had previously had BGP immunotherapy when compared to untreated patients, 3.6 +/- 5.1% (p less than 0.01). IgE anti-Bermuda grass appears to be the major contributor to susceptibility to BGP bronchial challenge. IgG4 anti-Bermuda grass is apparently unrelated to the sensitivity to challenge but appears to be a significant component of the immunologic response to immunotherapy.

Studies of complement activation and IgG subclass restriction of anti-thyroglobulin.

Using a sensitive radioimmunoassay, it was demonstrated that autoantibodies to human thyroglobulin (hTg) did not activate complement upon interaction with solid phase adsorbed hTg. Since IgG4 immunoglobulins do not activate complement, we studied sera containing large amounts of anti-thyroglobulin (anti-Tg) with a sensitive radioimmunoassay for IgG4 anti-Tg. Antibodies of the IgG4 subclass were detected in the sera of each of the eight patients studied and not in control subjects. Quantitative assays of IgG4 anti-Tg were performed by comparing the removal of anti-Tg and total IgG4 during immunoadsorption of anti-Tg. The contribution of IgG4 anti-Tg antibodies to the total quantity of anti-Tg ranged from 6 to 30%, an amount inadequate to explain the lack of complement activation by anti-Tg.

Complement activation by antibodies to Sm in systemic lupus erythematosus.

An enzyme linked immunosorbent assay was developed to quantitate antibodies to Sm (anti-Sm) and to measure complement activation by anti-Sm in vitro. Anti-Sm in plasma of patients with systemic lupus erythematosus (SLE) were bound to purified Sm bound to polyvinyl chloride microtitre plates and assayed for bound IgG or IgM using enzyme linked anti-gamma or anti-mu. The activation of C4 by anti-Sm was measured by adding diluted normal human serum (complement) to the wells and quantitating the amount of C4 bound to the well surface using (Fab')2 goat anti-C4 followed by enzyme linked rabbit anti-goat IgG. The plasmas of 12 of 36 patients with SLE contained anti-Sm and all 12 activated complement (complement activating anti-Sm). Twenty-eight plasmas containing anti-Sm from 12 patients with SLE were studied. Ten of the 12 patients had anti-Sm of the IgG class whereas two had anti-Sm of both IgG and IgM classes. The amount of C4 activating anti-Sm correlated significantly with the in vivo activation of C4 measured by rocket immunoelectrophoresis for C4d and C4, suggesting that complement activation by anti-Sm is important in vivo.

Activation of the classical pathway of complement by rheumatoid factors. Assessment by radioimmunoassay for C4.

A simple, sensitive solid-phase radioimmunoassay to quantitate the activation of the classical pathway of complement by rheumatoid factor (RF) is described. RF (purified, in serum or synovial fluid) was bound to reduced and alkylated IgG adsorbed to polyvinyl chloride microtiter plates and reacted with diluted normal human serum (complement). The activation and binding of C4 were quantitated with 125I-Fab'2-anti-C4. Purified, polyclonal IgM--RF was 100- to 1,000-fold more effective than purified IgG--RF in activating complement. The amount of complement activation produced by RF in each of the 57 sera and 2 synovial fluid samples correlated directly with the amount of IgM--RF present. The complement activating abilities of polyclonal IgM--RF in the sera of 15 rheumatoid arthritis patients were homogeneous. This novel technique is readily applicable to the investigation of complement activation by RF in disease.

Frentizole therapy in systemic lupus erythematosus.

Seven corticosteroid dependent patients with active systemic lupus erythematosus (SLE) were given frentizole in order to assess its effect on their clinical manifestations. Three patients exhibited slight clinical improvement, 2 patients did not change, and 2 deteriorated. Five of the 7 patients developed subclinical and reversible liver damage related to frentizole. This study, although preliminary and uncontrolled, suggests that frentizole is of limited value in the management of patients with SLE.