Richard Hong

IMMUNOGLOBULIN LEVELS FROM THE NEWBORN PERIOD TO ADULTHOOD AND IN IMMUNOGLOBULIN DEFICIENCY STATES

Beta-2A globulin and the 7S and 19S gamma globulins are the major proteins of the serum derived from the immune system. Collectively they have been termed the immunoglobulins. The 19S gamma globulin, also known as the gamma-1 macroglobulin, the 82 macroglobulin or 82M, has been the subject of intensive study in recent years. The rheumatoid factor as well as a variety of antibodies fall into this protein group, and abnormally high levels are found in Waldenstroems macroglobulinemia. Less is known about 82A globulin (gamma 1-A). It is like gammaglobulin in that it has a sedimentation constant of 7S, but contains more carbohydrate (1). Recent observations imply that it is the carrier of the reaginic activity of the serum (2). All of immunoglobulins are easily detectable in normal adult serum by immunoelectrophoretic analysis. 82A and 82M are absent in cord serum, and in agammaglobulinemia all three immunoglobulins are absent or in greatly reduced concentrations. Other antibody deficiency states have been described in which only one or two immunoglobulins are in low concentration (3-6). The present paper reports the levels of the immunoglobulins in cord serum and in the serum of infants, children, and adults as determined by a method based on a combination of immunoelectrophoretic analysis and the quantitative precipitin reaction (7). The data reveal a variable rate of maturation of the synthetic mechanisms for these proteins that is not apparent from semi-quantitative estimates based on simple immunoelectrophoretic analysis of serum. Also reported are the

Immunoglobulin E Deficiency in Ataxia-Telangiectasia

Abstract An IgE deficiency was demonstrated in 11 of 16 patients with ataxia-telangiectasia. No relation to age or to the level of IgG, IgM or IgD was found. Nine out of 11 patients with IgE and Ig...

Hereditary lymphopenic agammaglobulinemia associated with a distinctive form of short-limbed dwarfism and ectodermal dysplasia†

Lymphopenic agammaglobulinemia was associated with short-limbed dwarfism and ectodermal dysplasia in a brother and sister. Four similar cases have been reported as sporadic experiences. Our observations, together with these cases, indicate an autosomal recessive transmission and suggest a basic association between skin, bone, and immunologic development. the dwarfism in these children is not, as was previously suggested, characteristic of achondroplasia. One child died of a graft-versus-host reaction following blood transfusion, emphasizing the hazards of transfusion in lymphopenic immunologic disorders.

Prediction of persistent immunodeficiency in the DiGeorge anomaly

To assess the natural history of the immune defect in DiGeorge anomaly, we reviewed serial immunologic studies in 18 patients. The diagnosis was made with criteria based on the concept of the DiGeorge anomaly as a field defect. Initial or early follow-up laboratory examination suggested moderate to normal T cell function in 14 patients. None of these patients have lost T cell capability; they have never had infections characteristic of T cell deficiency. Four patients had clinical and laboratory evidence of profound immunodeficiency. A decreased number of CD4+ cells (less than 400/microliters) and a decrease in phytohemagglutinin responsiveness (stimulation index less than 10) may be useful in discriminating patients with immunodeficiency; absolute lymphocyte count and immunoglobulin values were not informative. At the time of surgery, the thymus was not found in 11 of 14 patients; however, only two of these patients had immunodeficiency. Patients with a persistently low number of CD4+ cells and decreased phytohemagglutinin response are candidates for immunologic reconstitution.

Treatment of Lymphopenic Hypogammaglobulinemia and Bone-Marrow Aplasia by Transplantation of Allogeneic Marrow

Abstract A patient with lymphopenic hypogammaglobulinemia was treated with two bone-marrow transplantations, with establishment of immunologic competence after the first transplant. After this transplant, an immunologically induced pancytopenia occurred, attributed to a reaction of the grafted lymphoid cells against host constituents. The patients bone marrow was then repopulated with a second marrow graft from the same donor. No further evidence of graft-versus-host disease was observed, and the recipient now possesses red blood cells and lymphocytes of donor type. The successful outcome of these transplantations depends to a large extent on the existence of histocompatibility between donor and host.

RECONSTITUTION OF B AND T LYMPHOCYTE FUNCTION IN SEVERE COMBINED IMMUNODEFICIENCY DISEASE AFTER TRANSPLANTATION WITH THYMIC EPITHELIUM

A patient with severe combined immunodeficiency has been given a transplant of thymic epithelium obtained from short-term culture of normal human thymus. 4 wk after transplantation immunoglobulin was detected and the patient now has normal levels of the three main classes. Functional antibodies of four specificities have been detected. An increase in reactivity to allogeneic cells and phytohaemagglutinin has been observed, with an increase in E rosettes; a positive delayed skin test to candida antigen is now present. The patient has shown reversal of wasting and has been free of infection for 7 months since receiving the transplant. It appears that under certain circumstances thymic epithelium reconstitutes both T and B cell functions.

Fatal Lymphoma after Transplantation of Cultured Thymus in Children with Combined Immunodeficiency Disease

A fatal, widespread, polyclonal, B-cell immunoblastic lymphoproliferative disorder developed in three children with combined immunodeficiency shortly after intra-abdominal transplantation of cultured thymus epithelium for immunoreconstitution. All three had surface immunoglobulin-bearing cells (15 to 20 per cent) in the peripheral blood before transplantation and polyclonally elevated immunoglobulins afterward. Abnormal immunoregulation was demonstrated by a lack of concanavalin A-induced suppressor-cell activity in mixed leukocyte culture in all three patients before transplantation and in two afterward. We suggest that the transplant acted as a promoter through immunostimulation or production of promoter factors, and that excessive polyclonal B-cell proliferation resulted because of inadequate immunoregulatory mechanisms. Although this complication occurred in only three of 30 patients with various forms of immunodeficiency treated with cultured thymus, these cases illustrate a potential problem in immunoreconstitution of combined immunodeficiency disorders.

The "active" rosette test in immunodeficiency diseases.

Abstract The “active” rosette test is a clinically useful test for assessing T cell function. When there is disparity between the result of the “active” and “total” rosette test, the clinical status and in vitro studies of the patient correlate better with active rosette formation. These studies also suggest that active rosette formation may serve as a marker of T cell differentiation.

The immune nature of subacute bacterial endocarditis (SBE) nephritis

Abstract Antibody was eluted from the kidney of a patient who died of renal failure with nephritis secondary to subacute bacterial endocarditis (SBE). The eluate was shown to specifically recombine with the bacteria cultured from the patients blood antemortem. Antiglomerular basement membrane antibody was also present, but rheumatoid factor activity could not be demonstrated in the eluate. These findings support the concept of antigen-antibody complex mediated renal damage in the pathogenesis of SBE nephritis.

Lymphocyte studies in congenital thymic dysplasia: The one-way stimulation test.

Lymphocytes from children with congenital thymic dysplasia were stimulated withmitomycin-C treated lymphocytes in the one-way stimulation test and with phytohemagglutinin (PHA). Cells of a patient with the sex-linked form of congenital thymic dysplasia consistently responded to allogeneic lyphocytes although the response to PHA was usually negative. Lymphocytes of two other patients did not respond to any form of stimulation; conversion of the PHA response took place in one of these children after transfusion with maternal and fetal lymphoid cells and was followed by a fatal graft-versus-host disease. Plasma from these children supported the growth of normal lymphocytes adequately. By our methods the carrier state could not be detected in patients relatives. There is suggestive evidence that lymphocyte response, as demonstrated by these in vitro tests, depends upon the integrity of the thymus. Failure to respond to PHA in the presence of a response to allogeneic cells suggests functional heterogeneity within the lymphoid system. Allogeneic stimulation may be more useful than PHA in the study of patients with congenital thymic dysplasia.