Long-term results of bone marrow transplantation in complete DiGeorge syndrome.

Background: Therapeutic options for DiGeorge syndrome (DGS) with profound T-cell deficiency are very limited. Thymic transplantation has shown promising results but is not easily available. Hematopoietic cell transplantation (HCT) has been successful in restoring immune competence in the short term.

History of infection before the onset of juvenile dermatomyositis: results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Research Registry.

Objective: To obtain data concerning a history of infection occurring in the 3 months before recognition of the typical weakness and rash associated with juvenile dermatomyositis (JDM).

Methods: Parents or caretakers of children within 6 months of JDM diagnosis were interviewed by the registry study nurse concerning their child's symptoms, environment, family background, and illness history. Physician medical records were reviewed, confirming the JDM diagnosis.

Immune complex disease associated with Epstein-Barr virus infectious mononucleosis.

We describe a patient with immune complex-mediated glomerulonephritis and leukocytoclastic vasculitis associated with Epstein-Barr virus (EBV) infectious mononucleosis. The patient required hemodialysis and has residual hypertension. This case implicates acute EBV infection as a cause of immune complex-mediated glomerulonephritis.

Inherited complement C3 deficiency: reduced C3 mRNA and protein levels in a Laotian kindred.

To determine the molecular basis of complement C3 deficiency in a Laotian kindred, the homozygous C3-deficient male propositus was studied. By ELISA, this individual's serum was determined to contain approximately 4 microg/ml C3 (0.3% of normal).

Aortic regurgitation at diagnosis of HLA-B27 associated spondyloarthropathy.

A 14-year-old boy with a 9 month history of rheumatic symptoms was found to have hemodynamically significant aortic regurgitation in association with an HLA-B27 associated spondyloarthropathy (SpA). Valvular incompetence due to aortitis can occur early in the clinical course of pediatric patients with SpA, and careful cardiac monitoring is warranted.

Defective production of granulocyte-macrophage colony-stimulating factor and interleukin-1 by mononuclear cells from children treated for acute lymphoblastic leukemia.

The production of colony-stimulating activity (CSA) by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from patients receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL) was examined. Supernatants from only 14 of 22 patient PBMC cultures (64%), but all supernatants from normal PBMC cultures, supported myeloid colony growth. When present, colony-stimulating activity always included granulocyte-macrophage colony-stimulating factor (GM-CSF).

Indomethacin-sensitive monocyte killing defect in a child with disseminated atypical mycobacterial disease.

A child with disseminated disease due to Mycobacterium avium had progressive disease in spite of 4.5 years of therapy with multiple antimicrobial agents selected on the basis of in vitro sensitivity testing of her organism. A defect in monocyte bactericidal activity was detected which was corrected in vitro by exposure of the patient's monocytes to indomethacin and normal serum.

Elevated interleukin-2 production by cord blood mononuclear cells from premature newborns.

This study was undertaken to delineate the elements of the interleukin-2 (IL-2) system in premature newborns by quantitating IL-2 production and IL-2 receptor (IL-2R) expression and density in cord blood mononuclear cells (CBMC) from 19 premature (estimated gestational age = 27-36 weeks, mean = 33.7), but otherwise healthy, infants and 25 term newborns. Phytohemagglutinin (PHA)-induced IL-2 production by premature CBMC was significantly greater (p less than 0.

Differential effect of continuous versus cyclic maintenance chemotherapy on cytokine-induced myeloid colony growth.

Myeloid colony growth by bone marrow cells obtained from pediatric cancer patients was stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or interleukin 1 (IL-1). Although patients recovering from cyclic high-dose chemotherapy showed normal colony growth in response to GM-CSF, patients with acute lymphoblastic leukemia (ALL) receiving continuous maintenance chemotherapy at moderate dose had variable but often severe decreases in myeloid colony growth compared with controls. Marrow from all patients and controls demonstrated enhanced colony growth in GM-CSF-stimulated cultures which also contained IL-1.

Successful bone marrow transplantation with split lymphoid chimerism in DiGeorge syndrome.

A female infant with DiGeorge syndrome associated with severe T-cell immunodeficiency underwent a successful bone marrow transplantation from her HLA-identical, mixed leukocyte culture-nonreactive brother at 5 months of age. Mature circulating T cells and mitogen-induced proliferative responses were detectable at 10 days posttransplant, and by 8 months post-transplant functional T- and B-cell reconstitution was documented by normal responses to mitogens and normal levels of serum immunoglobulins as well as in vitro and in vivo T-cell reactivity to specific antigens and production of specific antibody to T cell-dependent antigens in vivo. Phytohemagglutinin-induced interleukin-2 production and cell surface interleukin-2 receptor expression improved posttransplant, with normal production values observed by 8 months posttransplant.

Prolonged defects of interleukin-2 production, responsiveness, and receptor expression in patients with acute lymphoblastic leukemia.

The proliferative responsiveness to, production of, and the expression of cell-surface receptors for interleukin-2 (IL-2) were examined in 14 children with acute lymphoblastic leukemia (ALL) in remission and receiving maintenance chemotherapy for 6 to 35 months; in 19 children with ALL in remission and off all therapy for 2 to 138 months; and 15 control subjects. Short-term concanavalin A (Con A)-activated, purified T lymphocytes from patients on, as well as patients off, therapy had a significantly decreased proliferative responsiveness to a saturating amount of exogenous, recombinant IL-2 as compared to control subjects (P less than 0.005 and less than 0.

Elevated production of interleukin-2 by lymphocytes from children with acute leukemia.

Abnormalities of the production of interleukin-2 (IL-2) may play an important role in the immunologic dysfunction observed in pediatric leukemia patients. For an evaluation of the ability of lymphocytes from leukemic children to produce this cytokine, the production of IL-2 by mitogen-stimulated peripheral blood mononuclear cells was determined in children with acute leukemia at the time of diagnosis, during clinical remission, and at the time of relapse. Of 16 patients, 11 (69%) with either acute lymphoblastic leukemia or acute nonlymphoblastic leukemia at the time of diagnosis had IL-2 production levels above the highest level observed in control subjects, and all but one had values above the control mean.

Interleukin 2 production, proliferative response, and receptor expression by cord blood mononuclear cells.

To analyze the elements of the interleukin 2 (IL-2) system in newborns, the proliferative responsiveness to, production of, and expression of cell surface receptors for IL-2 were quantitated in cord blood mononuclear cells (CBMC) from 25 normal, full-term newborns and were compared to results in peripheral blood mononuclear cells (PBMC) from 15 juveniles and 28 adults in order to examine the IL-2 system as a function of age. Proliferative responsiveness of purified cord blood T lymphocytes to a saturating amount of human, recombinant IL-2 was significantly greater (p less than 0.05) than that of T lymphocytes from juveniles or adults at all three cell concentrations used.

Granulocyte macrophage colony-stimulating activity production by cultured human thymic nonlymphoid cells is regulated by endogenous interleukin-1.

Supernatants of cultured human thymic nonlymphoid cells were assayed for granulopoietic factors using cultures of low density bone marrow mononuclear cells (LD-BMMC). Thymic nonlymphoid cell-conditioned medium (TNLC-CM) supported vigorous myeloid colony growth of LD-BMMC, and of LD-BMMC depleted of T lymphocytes and/or monocytes. Colony stimulating activity (CSA) in TNLC-CM was abrogated by a highly specific neutralizing antiserum against recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF).

Inherited C3 deficiency with recurrent infections and glomerulonephritis.

A 10-year-old Laotian boy had homozygous deficiency of the third component of complement and recurrent bacterial infections beginning at age 5 months. Cellular and humoral immunity were normal, as were polymorphonuclear leukocyte chemotaxis and bactericidal activities. Serum complement-mediated hemolytic, chemotactic, and opsonic activities were deficient.

Detection of human immunodeficiency virus in cell-free seminal fluid.

Human immunodeficiency virus (HIV) was detected by assay of reverse transcriptase activity in a "virus pellet" obtained by differential sucrose density centrifugation of cell-free semen from three patients with the acquired immune deficiency syndrome (AIDS), one individual with AIDS-related complex (ARC), and in an asymptomatic homosexual male. Reverse transcriptase assays indicated virus concentrations in the range of 10(8) particles/ml of semen, an accumulation substantiated by electron microscopic visualization of cell-free virus. This is the first description of cell-free retrovirus in seminal fluid and at a greater concentration than reported for blood or other body fluids or tissues.

Interleukin 2 production and responsiveness in individuals with acquired immunodeficiency syndrome and the generalized lymphadenopathy syndrome.

Proliferative responsiveness to, and production of, interleukin 2 (IL-2) was determined in 9 homosexually active men with the acquired immunodeficiency syndrome (AIDS) and in 28 homosexually active men with the persistent generalized lymphadenopathy syndrome (PGL). All were seropositive for antibody to human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). Purified T lymphocytes from individuals with AIDS and PGL had a significantly decreased (P less than 0.

The effects of thymic epithelial monolayer-conditioned medium on suppressor cell function following chemotherapy in pediatric patients.

Human thymic epithelial monolayer-conditioned medium (TEM-CM) enhanced concanavalin A (ConA)-induced suppressor T-lymphocyte activity in 15 of 17 studies of fractionated light-density bone marrow mononuclear cells (LD-BMMC) obtained from pediatric cancer patients within 7 days of chemotherapy (P less than 0.001). However, TEM-CM depressed ConA-induced suppressor T-lymphocyte activity in 14 of 18 studies of LD-BMMC obtained from patients who had received their chemotherapy 14-21 days previously (P less than 0.

Mixed-pattern immune deposit glomerulonephritis in a child with inherited deficiency of the third component of complement.

The renal histopathology of a 7-year-old Laotian male with inherited deficiency of the third component of complement, recurrent infections, and persistent hematuria and proteinuria is described. The histologic changes are predominantly those of mesangiopathic disease with isolated changes resembling type I membranoproliferative glomerulonephritis and transmembranous glomerulonephritis. IgG, IgA, IgM, C4, and fibrinogen, but not C3, were detected by immunofluorescence in mesangial zones and in segments of capillary walls.

Bone marrow transplantation for severe combined immune deficiency in an infant with chimerism due to intrauterine-derived maternal lymphocytes: donor engraftment documented by chromosomal marker studies.

Chromosomal heteromorphisms defined by the quinacrine banding technique were used to identify the maternal origin of 46,XX lymphocytes present in the blood of a male infant with severe combined immune deficiency disease. These chromosomal markers were also used to document the engraftment by donor lymphocytes from the sister and the concurrent disappearance of maternal lymphocytes after a successful bone marrow transplantation. Donor lymphocytes were detected by this technique 6 days after transplantation, earlier than is usually possible with other marker systems and before definite evidence of immunoreconstitution.

Recurrent sepsis with deficiencies of C2 and galactokinase.

A 4-year-old girl with recurrent, severe bacterial infections and absence of both the second component of complement and galactokinase was investigated for immunodeficiency. The C2 deficiency (C2D) was diagnosed after four major pyogenic infections. Results of studies of cellular and humoral immunity were normal, as were polymorphonuclear leukocyte chemotaxis and bactericidal activities and alternative-pathway hemolytic activity.

The cerebro-hepato-renal syndrome of Zellweger: similarity to and differentiation from the DiGeorge syndrome.

A child with the cerebro-hepato-renal syndrome of Zellweger, who was originally diagnosed as having the DiGeorge syndrome, was studied and transplanted unsuccessfully with cultured thymus. The pertinent literature is reviewed and the importance of distinguishing the two disorders emphasized. Autopsy studies reveal that transplanted cultured thymic fragments can attract lymphoid aggregates as early as 2 wk after transplantation.