Humoral immunity in juvenille rheumatoid arthritis.
Authors: H M Hoyeraal, O J Mellbye
Journal: Annals of the Rheumatic Diseases (1974)

Autoantibodies are not infrequently found in sera from patients with juvenile rheumatoid arthritis (JRA), and recent studies suggest that humoral immune responses are responsible, in part, for the inflammatory synovitis observed in these patients.Whether these antibodies result from non-specific antigenic stimulation of an abnormal immunological apparatus, or from specific antigenic stimulation in a normal immunological apparatus, is not known.We know of no controlled study of the antibody response after antigen stimulation in patients with JRA.Reports from such studies in adult patients with rheumatoid arthritis (RA) have given conflicting results.Meiselas, Zingale, Lee, Richman, and Siegel (1961) found increased responses to Brucella immu- nization, whereas Shearn, Epstein, and Engleman (1963) and Waller, Ellman, and Toone (1966) found normal responses, and Bandilla, Pitts, and McDuffie (1970) found a selective deficiency in IgM antibody production.Similar conflicting results have been reported in the response to tetanus toxoid.Green- wood and Barr (1960) showed higher responses than in the controls, and Vaughan and Butler (1962) found no difference in the response, whereas Barr, Buchanan, Doniach, and Roitt (1964), and Whaley, Glen, MacSween, Deodhar, Dick, Nuki, Williamson, and Buchanan (1971) found lower responses.De- creased responses in patients with RA have also been observed after immunizations with incompatible blood group antigens A and B (Creger, Choy, and Rantz, 1951; Rawson, Abelson, and McCarty, 1961).Recently, Hazleman and Currey (1973) reported normal antibody responses after primary monovalent typhoid immunization in seropositive patients with RA.These conflicting results could be due to the different immunization procedures used, individual variations in the responses to various antigens, and the use of inadequate controls.The purpose of the present investigation was to study the immunological apparatus in patients with JRA.This presentation describes the results obtained by testing for antibody production after immuniza- tion with microbial antigens, in a group of patients and in a matched group of healthy controls.In addition, comparisons of the serum levels of immu- noglobulins and naturally-occuffing antibodies were performed.A report of delayed hypersensitivity in the same individuals is given elsewhere (Hoyeraal, 1973). Materials and methods PATIENTS AND CONTROLS34 hospitalized patients with JRA, diagnosed according to the criteria of Ansell and Bywaters (1969), and 34 non- hospitalized healthy controls matched in age and sex were studied.There were 22 female and 12 male pairs with a mean age of 9-1 years (2 range to 16).Examination for rheumatoid factor was performed by a modified Waaler- Rose test, latex slide test (Hyland, Los Angeles, Calif., USA), and Ripley test, and antibody to pepsin site of IgG was titrated as described by Mellbye and Natvig (1970).Antinuclear antibodies were tested using undiluted sera by indirect immunofluorescence on acetone-fixed (10 min.at 4°C.) frozen sections from mouse liver (Munthe, 1970) and by an indirect LE test (Larsen and Boyum, 1972).Titration of immunoconglutinin was performed as described by Coombs, Coombs, and Ingram (1961).The frequency of these autoantibodies in the two groups are summarized in Table I.Further clinical and laboratory details of the patients and the controls have been given in a previous report (Hoyeraal, 1973). COLLECTION AND STORAGE OF SERASerum was separated within a few hours and stored at -20°C.until analysed.Sera from each patient/control pair were always tested together. ANTIBODY PRODUCTION AFTER IMMUNIZATIONThe antigen used for testing of the primary humoral response was Brucella, since the typhoid paratyphoid A and B vaccine first tried, gave unpleasant side-effects.For testing the secondary response, diphtheria and tetanus vaccines were used (Fudenberg, Good, Goodman, Hitzig, Kunkel, Roitt, Rosen, Rowe, Seligmann, and Soothill, 1971).Blood was taken before and 2 weeks after sub- cutaneous injection of the vaccines.The vaccines and