Biomedical subjects

R Krakauer

Publications and source records attributed to R Krakauer.

23 records · Page 2Linked to original sources

PubMed1976

Secretory component deficiency. A disorder of the IgA immune system.

We studied a 15-year-old boy with chronic intestinal candidiasis who had normal serum IgA levels without IgA in his secretions. There was an elevated number of peripheral blood lymphocytes bearing surface IgA. In addition, the lymphocytes cultured in vitro with pokeweed mitogen produced IgA as well as other immunoglubulins. Despite this evidence of normal IgA synthetic capacity, the patient had greatly diminished levels of IgA in the saliva and jejunal fluid, and, as estimated by 14C-L-leucine incorporation, could not synthesize IgA locally at intestinal-mucosal sites. Finally, the patient had no detectable free secretory component in saliva or jejunal fluid in contrast to normal persons and to patients with IgA deficiency. The basis of this disorder is probably a defect in the homing of IgA precursor cells to secretory sites or in the selective proliferation/differentiation of IgA cells at such sites.

Adolescent↗

PubMed1976

The role of suppressor cells in the pathogenesis of common variable hypogammaglobulinemia and the immunodeficiency associated with myeloma.

The role of suppressor cells in the pathogenesis of immunodeficiency was analyzed using a technique that permits study of the differentiation of B lymphocytes into immunoglobulin-synthesizing plasma cells. Lymphocytes from normals synthesized 4,910 ng of IgM, 1,270 ng of IgA, and 1,625 ng of IgG per 2 X 10(6) cells when cultured for 7 days in the presence of pokeweed mitogen. In contrast the lymphocytes from patients with common variable hypogammaglobulinemia did not synthesize significant quantities of immunoglobulin. When lymphocytes from 9 of 13 patients with common variable hypogammaglobulinemia studied were cocultured with normal lymphocytes, the synthesis of immunoglobulin by the normal lymphocytes was depressed by 75-100%. A comparable suppression of immunoglobulin synthesis by normal lymphocytes was observed when they were cocultured with T cells from hypogammaglobulinemic patients. These studies suggest that in some patients the disease common variable hypogammaglobulinemia may not be due to an intrinsic defect of B cells alone but may be cuased or perpetuated by an abnormality of regulatory T cells that act to suppress B-cell maturation and antibody production. Peripheral blood lymphocytes from myeloma patients also had a drastically reduced capacity to produce polyclonal immunoglobulins. Three of 6 myeloma patients tested had circulating mononuclear cells that suppressed immunoglobulin production by cocultured normal lymphocytes. Purified T cells from myeloma patients did not mediate this suppressor effect. These observations suggest that one mechanism for the humoral immune deficiency observed in myeloma patients is a block of polyclonal B-cell maturation by suppressor cells.

Agammaglobulinemia↗

PubMed1976

Defect in IgA secretion and in IgA specific suppressor cells in patients with selective IgA deficiency.

The nature of the defect in patients with selective IgA deficiency was investigated using a technique established to study terminal differentiation of B lymphocytes into immunoglobulin synthesizing and secreting cells. The peripheral blood lymphocytes from normal individuals had geometric mean synthetic rates of 4910 ng for IgM, 1625 ng for IgG and 1270 ng for IgA per 2 x 10(6) cells in culture for 7 days in the presence of pokeweed mitogen. The cultured lymphocytes from each of the 14 patients with selective IgA deficiency studied synthesized normal quantities of IgG and IgM but secreted less than 100 ng of IgA into the media. However, 11 of the 14 patients studied synthesized IgA by the 7th day in PWM stimulated cultures as assessed by staining for cytoplasmic IgA using fluorescein-labeled anti-IgA antisera. Synthesis and secretion of IgA by normal cells was not suppressed when they were co-cultured with lymphocytes from these patients that synthesize but do not secrete IgA. Three of the 14 patients did not have lymphocytes with IgA demonstrable in their cytoplasm following culture. When the lymphocytes from these 3 patients were co-cultured with normal lymphocytes and pokeweed mitogen the synthesis of IgA by the normal cells was depressed by 80 to 100%. Synthesis of IgG and IgM was not depressed. These studies suggest that lymphocytes cultured with pokeweed mitogen from the majority of patients with selective IgA deficiency can synthesize IgA but have a defect in IgA secretion. A smaller group of the patients do not synthesize IgA and have IgA specific suppressor cells that prevent B cells from maturing into IgA synthesizing and secreting cells.

Adolescent↗

PubMed1975

Suppressor T cells in the pathogenesis of hypogammaglobulinemia associated with a thymoma.

The nature of the immunological defect in patients with hypogammaglobulinemia associated with a thymoma was investigated using a technique established to study the differentiation of lymphocytes into immunoglobulin synthesizing and secreting cells. Exhaustively washed peripheral blood lymphocytes were cultured for 7 days in RPMI-1640 medium supplemented with fetal calf serum in the presence of the lectin, pokeweed mitogen. The IgG, IgA, and IgM synthesized and secreted into the medium were measured by competitive double antibody radio-immunoassays. Twenty-two normal individuals synthesized 1625 ng of IgG, 1270 ng of IgA, and 4910 ng of IgM per 2 million lymphocytes in culture. In contrast, the three patients with hypogammaglobulinemia and a thymoma synthesized less than 100 ng of each class of immunoglobulin. When lymphocytes from 2 of the 3 patients studied were cocultured with normal lymphocytes and pokeweed mitogen, the synthesis of immunoglobulin by normal lymphocytes was depressed by a factor of 66 to 97%. Co-cultue of purified T cells from the hypogammaglobulinemic patients with normal lymphocytes resulted in an 87% suppression of immunoglobulin synthesis by the normal cells. However, no suppression of immunoglobulin synthesis was observed when preparations of B cells and macrophages depleted of T cells from the hypogammaglobulinemic patients were co-cultured with normal lymphocytes. In addition, in control studies no such suppression of immunoglobulin synthesis was seen when normal cells were co-cultured with lymphocytes from unrelated normals, patients with isolated IgA deficiency, patients with chronic lymphocytic leukemia or patients with the Sezary syndrome, a T cell leukemia nor were they inhibited when incubated with T cells from unrelated normals. These observations suggest that in some patients the hypogammaglobulinemia associated with a thymoma may be caused or perpetuated by an abnormality of regulatory T cells which suppress the maturation of lymphocytes into antibody producing cells.

Adolescent↗

PubMed1975

Deficiency of secretory Ig-A and intestinal malabsorption.

A patient under treatment with hemodialysis suffered increasing clinical and laboratory evidence of intestinal malabsorption. Jejunal aspirates revealed heavy bacterial and mycotic flora within the proximal jejunum. Secretory Ig-A and secretory component were present only in trace amounts. The deficiency of the generally ubiquitous secretory component is particularaly striking. Oral administration of 20-30 ml. colostrum daily reversed not only the clinical evidence but also laboratory findings of intestinal malabsorption.

Colostrum↗