Immunmodulation durch inkomplettes Freund-Adjuvans im Frühstadium der rheumatoiden Arthritis

Abstract Investigations were carried out in a longitudinal study on the clinical and immunological effects of therapy with Freund's incomplete adjuvant (FIA) in early cases of rheumatoid arthritis (RA). Forty-four patients in the anatomical A.R.A.-class I (42 cases) and II (2 cases) and in the functional A.R.A.-class (44 cases) were randomly allocated into 3 treatment groups: experimental (FIA, 1 cc inj. sc/weekly for 5 weeks) positive (gold salts) and negative (placebo) controls. A course of the disease was mainly evaluated by clinical index (CI), ESR and an immunoregulatory index (IRI) calculated as the ratio of T-cell subsets determined by high affinity (HA) to low-affinity (LA) rosette formation with sheep erythrocytes. Clinical improvement started as early as 3 weeks after FIA therapy and was evident at 3 months in 76% of treated patients (25/33 cases); remission of the disease was progressive during the 1 year follow-up. Significant decrease (p < 0,001) of CI was associated with reduction of ESR and normalisation of IRI. Such objective changes were also detected in 82% of cases treated with gold but they were absent in patients treated with placebo. Beside the formation of nodules (which disappeared at the end of 1 year) and delayed hypersensitivity reactions at the site of FIA injections, no other side effects were encountered. The imbalanced T-cell subset ratio found initially in most of our patients mainly resulted from an abnormal proportion of LA rosettes formed by suppressor lymphocytes. It can therefore be assumed that restoration of a correct T-cell balance and suppressor cell activity which brought about remission of the disease was caused by the systemic immunoregulatory mechanisms triggered by local effects of FIA administration as revealed by the formation of granulomas associated in most patients with clinically positive response, with delayed hypersensitivity reactions.