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Renal function was studied in twenty-nine of thirty-four surviving renal allograft recipients from an initial group of sixty-four patients two years after transplantation. Mean clearances of inulin and PAH were, respectively, greater than and equal to half the donors’ initial predicted clearances. Minimum urine osmolality during water diuresis was greater, and maximum urine osmolality during hydropenia was less than normal, an effect attributable partly to enhanced solute load in a single transplanted kidney.

A clinically distinct pneumonitis occurred in six renal transplant recipients receiving azathioprine and prednisone immunosuppressive therapy. The patients ranged in age from 3 to 20 years. The onset was 42 to 102 days postoperatively, coinciding with decrease in prednisone dosage below approximately 1 mg per kilogram of body weight per day. Mild nonproductive cough, fever, and cynanosis were present. Chest x-rays demonstrated extensive hazy to nodular infiltrates usually involving both hila and lower lung fields. Cold agglutinins were present in five patients. Pulmonary function studies demonstrated an alveolar capillary block. The duration of illness was 12 to 34 days and was not influenced by antibiotic therapy. Autopsy of the single case in which death occurred revealed Pneumocystis carinii pneumonia and disseminated cytomegalic inclusion-body disease.

ALG raised against lymphoblasts grown in pure culture for many generations contained antiplatelet activity. The thromboagglutinins could be completely removed by absorption with lymphoblasts, indicating that they had been raised to antigens shared by lymphoblasts and platelets. Anti-spleen ALG possessed levels of such anti-platelet antibodies but in substantially higher titres, because an additional contribution was made by contaminating thrombocytes in the immunizing injectate. By chromatographic separation and immunoelectrophoretic analysis of the eluate from platelet–antibody complexes generated during the absorption of anti-spleen ALG with thrombocytes, the thromboagglutinins were shown to reside almost exclusively (97·7%) in the area of the IgA fraction. The direct Coombs' test, reacting platelets from patients receiving equine anti-spleen ALG with guinea-pig antisera against normal horse serum, showed a highly significant, but not invariable correlation with clinical platelet depression, which was not, however, clearly related to the thromboagglutinin titre of the ALG being administered.

Horse anti-dog and anti-mouse ALS were digested for varying intervals with acid Taka-protease, a proteolytic enzyme. A progressive reduction in antigenicity was demonstrated, as determined by in vitro precipitin reactions with standard antisera and by passive cutaneous and systemic anaphylaxis tests. Leukoagglutinins and lymphocytotoxins were conserved in anti-dog ALS but there was a marked diminution in anti-platelet and anti-erthrocyte activity. Both anti-red cell and anti-white cell antibodies of anti-mouse ALS were reduced. Digestion appeared to completely degrade some protein fractions such as albumin and to alter the immunoglobulin molecule, possibly by cleavage of the terminal portion of the Fc fragment. Digestion of ALS with Taka-protease may prove to be a useful procedure particularly since it was demonstrated that immunosuppressive potency was partially retained. For further evaluation a better standardized Taka-protease will be required.

Tissues obtained from 34 human renal allografts by biopsy, 1 to 31 months after transplantation, were studied by histologic, immunofluorescence, and immunoferritin techniques. Our purpose was to gain more precise information concerning the localization of immunoglobulins and complement in glomeruli and to describe the associated tubular and vascular changes. Localization of fluorescein-labeled antibodies (Fl-Abs) to IgG, IgM, β1C, and C′1q was seen in glomeruli from 25 allografts and showed the following distribution of patterns: (a) diffuse linear, four; (b) diffuse granular, four; (c) focal linear, six; (d) focal granular, six; and (e) indeterminate, five. Ferritin-conjugated antibodies (Fer-Abs) localized in 21 allografts. Electron microscopic findings correlated with the foregoing immunofluorescence patterns. (a) Fer-Abs were bound on the endothelial side of the glomerular basement membrane and in the subendothelial space. (b) Fer-Abs were bound in subendothelial and subepithelial deposits similar to those seen in experimental acute or chronic serum sickness. (c and d) Fer-Abs were seen in the subendothelial space and mesangial matrix. Deposits were present in these areas and some bound Fer-Abs. The two groups were not readily separable on the basis of immunopathologic data. (e) Fer-Abs were mostly seen in the mesangial area.Nine allografts displaying little or no binding of Fl-Abs failed to bind Fer-Abs.Small amounts of fibrinogen were found in only six allografts, three of which showed diffuse granular fluorescence.In 12 allografts either Fl-Abs or Fer-Abs or both were bound in walls of blood vessels. The position of these reactants was in foreign deposits and in basement membranes of arteries and veins.

In the sera of ten normal humans and twenty-eight candidates for organ transplantation, the passive haemagglutination test detected a 50% incidence of preformed antibodies of low titre directed against horse serum. Such antibodies were also found to cross react with goat or rabbit sera in most instances. Seventeen of the organ recipients were later studied after the institution of treatment with horse antihuman-lymphocyte globulin (ALG). The incidence of anti-horse-serum antibodies rose to 100%. At the same time, an increased activity against goat serum developed; cross-reactions against rabbit serum were also demonstrated but to a less pronounced degree. With immunoelectrophoresis and Ouchterlony diffusion tests, it was shown that the cross-reactivity was to similar although not necessarily identical protein components of the different heterologous sera.