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19S anti-gamma-globulins were isolated in a high state of purity from the sera of two patients with rheumatoid arthritis. Following reduction with ethyl mercaptan and alkylation by iodoacetamide, fragments were produced which retained the capacity to combine with 7S gamma-globulin. The fragments from one of the 19S anti-gamma-globulins agglutinated red cells coated with incomplete anti-Rh antibodies. This activity was shown by density gradient ultracentrifugation to be associated with low molecular weight fractions. The agglutination of the coated red cells by the fragments was strongly inhibited by normal and myeloma 7S gamma-globulins and showed a greater specificity than the parent 19S material. Analytical ultracentrifuge experiments demonstrated that the fragments from either of the 19S anti-gamma-globulins formed complexes with 7S gamma-globulin. Reassociation of the dissociated fragments through reformation of disulfide bonds resulted in the formation of fast sedimenting molecules having properties similar to those of the untreated 19S material in respect to precipitation with aggregated gamma-globulin and agglutination of coated red cells.
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In order to measure the reciprocal nonspecific effect of the genetic regulation of antibody responsiveness to bovine serum albumin (BSA) and rabbit gamma-globulin (RGG), two independent bidirectional selective breedings for responses to these two antigens were carried out: selection V/BSA and selection V/RGG respectively. The total interline separation at selection limit (RT) was 5.3 log2 for selection V/BSA and 2.6 log2 for selection V/RGG. The sum of these two values (7.9 log2) is similar to the RT in selection V carried out by alternating these two antigens in consecutive generations. In selection V/BSA, the nonspecific effect for responsiveness to RGG was 72%. In selection V/RGG, the nonspecific effect for BSA responsiveness was 135%. The F1 hybrids between homologous lines of selection V/BSA and selection V/RGG presented a larger difference in antibody response to both antigens than their parental lines. This demonstrates an additive effect of the loci controlling the two responses.
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Twenty-seven lots of standard immunoglobulin from 5 different producers and 18 lots of specific immunoglobulin (non anti-Hepatitis B) were titrated by RIA test for anti-HBs content. The highest titre in lots of standard IG (1:40) was lower than the lowest titre of the lots of specific IG (non anti-Hepatitis B) (1:44). The difference between means (1:17 and 1:42) was statistically significant (p less then 0,01). The reasons for the difference are discussed.
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A gamma-globulin preparation for intravenous use was given to 11 patients with antibody deficiency syndromes. Most of them had reacted earlier to intramuscular injections of normal gamma-globulin. The gamma-globulin employed produced adverse reactions, often quite severe in 8 of 9 intravenous infusions in three patients. After premedication with hydrocortisone, side effects appeared on 18 of 48 occasions in 10 patients, but only twice were they so severe that the infusions had to be interrupted. Thus, it seems that hydrocortisone diminishes the risk of side effects. The intravenously administered gamma-globulin seemed to be just as effective as the preparations for intramuscular use, and no severe infections appeared during the period of observation. There was no indication that the single hydrocortisone injections, usually 200 mg, increased the risk of contracting infections, but still such medication should be used with great caution in antibody-deficient patients.
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