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42. Fetal thymic epithelium transplant in severe combined immunodeficiency (SCID)
Abstracts
VOLUME 61 NUMBER 3
replacing factors) the remaining one half of the B cells were accounted for by large lymphocytes (10 to 14 pm in diameter) which possessed both surface IgM as well as cytoplasmic IgM and lacked C3 receptors. These cells spontaneously secreted large amounts of IgM in vitro and on electron microscopy were found to be rich in rough endoplasmic reticulum. This latter subpopulation of cells which is absent from normal peripheral blood probably accounts for the major immunologic abnormality seen in the disorder.
2. Fetal thymic combined
epithelium transplant in immunodeficiency (SCID).
S. McGeady, M.D., M. Wolk, M.D., and H. C. Mansmann, Jr., M.D., Philadelphia,
Pa.
Thymus from an aborted 18wk-old fetus was grown in tissue culture for 23 days. With the use of intraperitoneal infusion the tissue was then transplanted into a 14-mo-old male child with adenosine deaminase-positive SCID. The child demonstrated a 21/2-mo period of clinical improvement with acquisition of lymphocyte phytohemagglutinin (PHA) responsiveness (Fig. I). The number of peripheral blood E rosettes did not increase. The child developed recurrent oral ulcerations and failure to thrive with simultaneous loss of PHA response. Children with SCID are known to represent a number of celiular and thymic defects. Transplantation of thymus grown in tissue culture to eliminate “passenger” lymphocytes has led to apparent reconstitution in some SClD cases, which suggests an intrathymic defect with competent stem cells. In our patient, the transient nature of response and the persistently low E rosettes suggest that T cell precursors were limited in number and incapable of replenishment. Transplantation with a stem cell source seems indicated.
9/76
12/76
z/77
4/77
g/77
iphenylhydantion (DPH) effects on immunity: A prospective study. Gabourel, Ph.D., E. J. Bardana, Jr., M.D., 6. I-1. Davies, A.I.S.T., D. M. Dordevich, M.D., Portland, Ore. DPH effects on humoral and cellular immunity were prospectively studied in 89 patients. Sequential analysis of
of papers
1
serum immunoglobulins, C-3, C-4, a variety of antinuclear antibodies, and blastogenic responses to mitogens were carried out. Patients were classified into three groups: (1) 39 patients with idiopathic epilepsy (IE); (2) 22 patients with secondary epilepsy (SE); (3) 28 patients without seizures (WS) given DPH prophylactically prior to and after neurosurgery or for treatment of neuropathic pain. Forty-one patients (22, 8, and 11 from each group, respectively) were evaluated at least once after starting DPH. Prior to starting treatment, 18% of IE, 9% of SE, and 3% of WS patients had depressed serum IgA levels (60 mg%). After 6 mo of DPH therapy the incidence of low serum IgA rose to 32%, 25%, and 14%, respectively. Five IE, 2 SE, and 1 WS patient(s) developed de novo antinuclear antibodies without symptoms after DPH treatment. Twenty-nine of 34 patients had decreased lymphocyte responses to phytohemagglutinin after taking DPH for 6 mo, whereas only 12 of 23 normal volunteers had decreased responsiveness on second evaluation. Our data are consistent with earlier suggestions in nonprospective studies that: (1) Patients with IE have a higher incidence of serum IgA deficiency prior to starting DPH. (2) Patients on DPH can be expected to develop de novo antinuclear antibodies. (3) DPII has a definite suppressive effect on both humoral and cell-mediated immunity
44. Recurrent infection, antibo and normal immunoglobulins. C. Rothbach, P. Fireman,
M.D., 0. Rabin, LX, Pittsburgh,
M.D., and Ba.
Antibody deficiency in the presence of normal immunoglobulins has been described infrequently. We recently evaluated a lo-yr-old white boy with chronic bronchiectasis and persistent pneumonitis. Family history was unremarkable. At 1 yr, during work-up of recurrent infections, IgG was 870 mg% with IgA and IgM present. At 10 yr, serum IgG, A, and M were 1:420, 235, and 63 mg%. Peripheral blood lymphocytes were 2,000/mm3 with 60% T rosettes and 20% B rosettes. Measurement of specific antibody revealed absence of tetanus and diptheria antitoxin before and after booster Td toxoid. Despite prior immunization no antibodies to measles or mumps were detected. Qctavalent pneumococcal vaccine induced antibody to only 2 of 8 antigens. Rubella antibodies were present at 1: 20 and isohemagglutinins were anti-A 1: 8 and anti-B 1: 128. Antistreptolysin-0 was 680 TODD U. The patient had a positive delayed skin test to streptokinase-streptodornase (SK-SD) but negative responses to Candida, tetanus, and purified protein derivative (PPD). In vitro lymphocyte responses were normal to phytohemagglutinin (PHA), pokeweed, and SK-SD but were unresponsive to tetanus. In vitro suppressor T cells to tetanus have not been identified. MLC was normal. Macrophage inhibitory factor (MIF) was not detected to tetanus or SK-SD. Lymph node biopsy and lymphocyte subclass distribution by immuno~uores~e~~e were normal. Assays of complement components Cl-9 were normal. Leucocyte phagocytic and bactericidal functions
VOLUME 61 NUMBER 3
replacing factors) the remaining one half of the B cells were accounted for by large lymphocytes (10 to 14 pm in diameter) which possessed both surface IgM as well as cytoplasmic IgM and lacked C3 receptors. These cells spontaneously secreted large amounts of IgM in vitro and on electron microscopy were found to be rich in rough endoplasmic reticulum. This latter subpopulation of cells which is absent from normal peripheral blood probably accounts for the major immunologic abnormality seen in the disorder.
2. Fetal thymic combined
epithelium transplant in immunodeficiency (SCID).
S. McGeady, M.D., M. Wolk, M.D., and H. C. Mansmann, Jr., M.D., Philadelphia,
Pa.
Thymus from an aborted 18wk-old fetus was grown in tissue culture for 23 days. With the use of intraperitoneal infusion the tissue was then transplanted into a 14-mo-old male child with adenosine deaminase-positive SCID. The child demonstrated a 21/2-mo period of clinical improvement with acquisition of lymphocyte phytohemagglutinin (PHA) responsiveness (Fig. I). The number of peripheral blood E rosettes did not increase. The child developed recurrent oral ulcerations and failure to thrive with simultaneous loss of PHA response. Children with SCID are known to represent a number of celiular and thymic defects. Transplantation of thymus grown in tissue culture to eliminate “passenger” lymphocytes has led to apparent reconstitution in some SClD cases, which suggests an intrathymic defect with competent stem cells. In our patient, the transient nature of response and the persistently low E rosettes suggest that T cell precursors were limited in number and incapable of replenishment. Transplantation with a stem cell source seems indicated.
9/76
12/76
z/77
4/77
g/77
iphenylhydantion (DPH) effects on immunity: A prospective study. Gabourel, Ph.D., E. J. Bardana, Jr., M.D., 6. I-1. Davies, A.I.S.T., D. M. Dordevich, M.D., Portland, Ore. DPH effects on humoral and cellular immunity were prospectively studied in 89 patients. Sequential analysis of
of papers
1
serum immunoglobulins, C-3, C-4, a variety of antinuclear antibodies, and blastogenic responses to mitogens were carried out. Patients were classified into three groups: (1) 39 patients with idiopathic epilepsy (IE); (2) 22 patients with secondary epilepsy (SE); (3) 28 patients without seizures (WS) given DPH prophylactically prior to and after neurosurgery or for treatment of neuropathic pain. Forty-one patients (22, 8, and 11 from each group, respectively) were evaluated at least once after starting DPH. Prior to starting treatment, 18% of IE, 9% of SE, and 3% of WS patients had depressed serum IgA levels (60 mg%). After 6 mo of DPH therapy the incidence of low serum IgA rose to 32%, 25%, and 14%, respectively. Five IE, 2 SE, and 1 WS patient(s) developed de novo antinuclear antibodies without symptoms after DPH treatment. Twenty-nine of 34 patients had decreased lymphocyte responses to phytohemagglutinin after taking DPH for 6 mo, whereas only 12 of 23 normal volunteers had decreased responsiveness on second evaluation. Our data are consistent with earlier suggestions in nonprospective studies that: (1) Patients with IE have a higher incidence of serum IgA deficiency prior to starting DPH. (2) Patients on DPH can be expected to develop de novo antinuclear antibodies. (3) DPII has a definite suppressive effect on both humoral and cell-mediated immunity
44. Recurrent infection, antibo and normal immunoglobulins. C. Rothbach, P. Fireman,
M.D., 0. Rabin, LX, Pittsburgh,
M.D., and Ba.
Antibody deficiency in the presence of normal immunoglobulins has been described infrequently. We recently evaluated a lo-yr-old white boy with chronic bronchiectasis and persistent pneumonitis. Family history was unremarkable. At 1 yr, during work-up of recurrent infections, IgG was 870 mg% with IgA and IgM present. At 10 yr, serum IgG, A, and M were 1:420, 235, and 63 mg%. Peripheral blood lymphocytes were 2,000/mm3 with 60% T rosettes and 20% B rosettes. Measurement of specific antibody revealed absence of tetanus and diptheria antitoxin before and after booster Td toxoid. Despite prior immunization no antibodies to measles or mumps were detected. Qctavalent pneumococcal vaccine induced antibody to only 2 of 8 antigens. Rubella antibodies were present at 1: 20 and isohemagglutinins were anti-A 1: 8 and anti-B 1: 128. Antistreptolysin-0 was 680 TODD U. The patient had a positive delayed skin test to streptokinase-streptodornase (SK-SD) but negative responses to Candida, tetanus, and purified protein derivative (PPD). In vitro lymphocyte responses were normal to phytohemagglutinin (PHA), pokeweed, and SK-SD but were unresponsive to tetanus. In vitro suppressor T cells to tetanus have not been identified. MLC was normal. Macrophage inhibitory factor (MIF) was not detected to tetanus or SK-SD. Lymph node biopsy and lymphocyte subclass distribution by immuno~uores~e~~e were normal. Assays of complement components Cl-9 were normal. Leucocyte phagocytic and bactericidal functions