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A 5-year-old girl with a history of recurrent infection and anaemia has no measurable purine nucleoside phosphorylase (N.P.) activity in her red blood-cells. Her serum-immunoglobulin levels are normal, as are her antibody responses to thymus dependent and independent antigens. However, she has severe lymphopenia, pronounced depression of lymphocyte response to mitogenic and allogeneic cell stimuli, and greatly decreased T-cell rosette formation. Her parents are second cousins; their red cells contain less than half the normal level of N.P. activity. They also share an unusual N.P. isozyme pattern indicative of molecular hybridisation between catalytically active and inactive subunits, which strongly supports the assumption that they are heterozygous and their daughter is homozygous for a "silent" allele at the N.P. gene locus. Inherited deficiency of adenosine deaminase, an enzyme catalysing a reaction only one metabolic step away from that of N.P., is known to cause immunodeficiency. It is therefore very likely that this patient's lack of demonstrable N.P. activity is responsible for her syndrome.

We evaluated the effects of recombinant interleukin 2 (IL-2) on the proliferative responses to mitogens of peripheral blood mononuclear cells (PBMC) from three adenosine deaminase (ADA)-deficient patients. There was significant enhancement by IL-2 of the proliferative responses to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) of PBMC from all three patients. We found that normal PBMC respond with increased numbers of CD3-positive cells when exposed to PHA or PWM and that the response by normal CD8-positive cells was greater than that by CD4-positive cells. In contrast, we found that in ADA-deficient cells the response is almost entirely due to the CD3/CD4-positive population of lymphocytes. These results could not be explained by either the culture conditions or the possibility of a mixed chimeric state. When we evaluated an in vitro cell model of ADA deficiency using an ADA inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), we found that the inhibitory effect of EHNA plus deoxyadenosine on mitogen-stimulated PBMC could not be prevented by IL-2. These results suggest that the immunodeficiency in ADA deficiency includes the absence or failure of a subset of T cells to make IL-2 and the failure of the CD8-positive subset to respond to IL-2. Also, the in vitro cell model of ADA deficiency using EHNA as the ADA inhibitor is limited in its use in understanding the pathogenesis of this disease.

To reduce the risk of infection from Streptococcus pneumoniae in hyposplenic patients we administered octavalent pneumococcal vaccine to 77 patients with sickle-cell disease and 19 asplenic persons and compared their response with 82 controls (38 age-matched normal persons and 44 normal black African children). Fifty micrograms each of pneumococcal-polysaccharide Types 1, 3, 6, 7, 14, 18, 19, and 23 were administered subcutaneously. Post-immunization serums (three to four weeks) were available from 52 of 77 patients with sickle-cell disease; the percent responding and the magnitude of the indirect hemagglutination response were comparable to those of the controls. Within two years after immunization we observed eight Str. pneumoniae infections in 106 age-matched unimmunized patients with sickle-cell disease, but none in the 77 immunized (P less than 0.025). We conclude that pneumococcal polysaccharides are immunogenic in hyposplenic patients and may protect against systemic Str. pneumoniae infection.

T-helper:T-suppressor cell ratios of 1 or less were found in 2 of 42 homosexual men without antibodies to cytomegalovirus but in 33 of 67 homosexual men with antibodies (p less than 0.001). Of 34 men without antibody who were followed prospectively, 12 became seropositive for cytomegalovirus and all 12 developed helper: suppressor ratios of less than 1.0. These ratios remained at 1 or less for an average of 9.6 months but persisted for 15 months or more in 3 men. None of the men in the prospective study developed antibodies to the acquired-immunodeficiency-syndrome-associated retrovirus. These results indicate that in the homosexual men studied, abnormally low T-lymphocyte helper: suppressor ratios occurred almost exclusively in those who were infected with cytomegalovirus, and in those prospectively followed low ratios did not reflect contact with the syndrome-associated retrovirus. Abnormal ratios were rarely seen in men who had never been exposed to cytomegalovirus. Thus, cytomegalovirus infection may be an important cofactor in the immunologic disorders leading to the acquired immunodeficiency syndrome.

The ability to define subpopulations of immunologically competent lymphocytes has permitted an enhanced understanding of the interaction between functionally distinct components of the immune system. T cells can provide help in antibody formation or they may suppress antibody production. Abnormal immunoregulatory mechanisms have been demonstrated in the hyperimmunoglobulin E-recurrent infection syndrome. This disorder is associated with a marked elevation of IgE and specific elevations of IgE antibodies directed toward staphylococcal antigens. Abnormal T cell regulation of immune responses has been demonstrated. Graft-versus-host disease (GVHD) occurs in an immunodeficient patient who has received an infusion of immunocompetent cells. The diagnosis of graft-versus-host (GVH) reaction may be complicated by the protean manifestations of the disorder. The acute form, consisting of a maculopapular rash, fever, and diarrhea, may be confused with acute infection or drug reaction. Chronic GVHD has been incorrectly diagnosed as histiocytosis X, acrodermatitis enteropathica, or scleroderma. Utilizing chromosome markers and/or identification of histocompatibility antigens, the presence of circulating lymphocytes from donor immunocompetent cells (blood transfusion, maternal source) can be documented. The development of sensitive technics for identifying cells can establish a precise diagnosis. Certain immunodeficiency disorders can be identified by biochemical means. Biotin-dependent multiple carboxylase enzyme deficiency is associated with a chronic dermatitis, alopecia, ataxia, and secondary infection of the skin with Candida. The disorder responds promptly to the administration of biotin with correction of dermatologic, neurologic, and immunologic abnormalities.

A luminol-enhanced chemiluminescence assay was used to investigate opsonic requirements for phagocytosis of STreptococcus pneumoniae serotypes VII, XIV, and XIX. After opsonization with whole immune sera (with antibody and total complement pathway), heat-inactivated immune sera (with antibody alone), or magnesium dichloride-ethylene glycol tetraacetic acid-chelated immune sera (with antibody and alternative complement pathway), live S. pneumoniae cells were incubated at 37 degrees C with normal polymorphonuclear leukocytes while serial chemiluminescence measurements were recorded. The amount of chemiluminescence observed correlated closely with evidence of phagocytosis as observed by microscopy. Complement was required for efficient opsonization, since all three serotypes showed a slower rise and less integral chemiluminescence after opsonization with heat-inactivated serum as compared with whole serum. The alternative pathway provided opsonic activity equal to that of the total complement pathway for type XIX, but only intermediate activity for types VII and XIV. Type-specific antibody was also required for effective opsonization of all three serotypes since chemiluminescence was markedly reduced when bacteria were opsonized with antibody-depleted serum (serum absorbed with type-specific S. pneumoniae cells at 4 degrees C). Thus, chemiluminescence proved to be an effective means of defining the requirement for both antibody and complement in the opsonization and phagocytosis of S. pneumoniae.

The effect of human immunodeficiency virus (HIV) recombinant envelope glycoprotein 120 (rgp 120) on the functions of peripheral blood mononuclear cells (PBMC) in vitro was investigated. The results demonstrate that rgp 120 used at concentrations less than 1 microgram/ml has no significant effects on PBMC function in vitro. However, the addition of 1-20 micrograms/ml of rgp 120 significantly inhibits the tetanus toxoid-induced PBMC proliferative response in a dose-related manner as determined by [3H]thymidine incorporation. The data also show that rgp 120 (5 micrograms/ml) causes up to 70% reduction in the number of immunoglobulin G-secreting cells in pokeweed mitogen-stimulated PBMC cultures. Further, rgp 120 can selectively interact with the CD4a epitope of the CD4 helper cell membrane receptor. These results indicate that microgram per milliliter levels of rgp 120 can depress certain immune functions in vitro. The significance of these findings to the pathogenesis of immunodeficiency in HIV infection remains to be determined.

The effect of increased nutritional intake was evaluated in 5 growth-retarded children with sickle-cell disease. Growth on recommended daily calorie and protein intakes had been inadequate in all 5. Fat absorption and intestinal mucosal morphology were normal in all 5. 2 children were given nutritional supplementation by nasogastric intubation, 1 received nightly oral formula supplements, and 2 were supplemented with zinc, iron, folate, and vitamin E only. Nutritional supplementation by the nasogastric route produced a rapid sustained increase in growth rate, associated with striking reductions in pain crises and infections which had previously necessitated many hospital admissions. Oral supplementation improved the clinical course but had no effect on growth rate. Mineral and vitamin supplements influenced neither the growth rate nor the clinical course. The observations indicate that nasogastric nutritional supplementation may accelerate growth and reduce the incidence and severity of complications in growth-retarded children with sickle-cell disease.

A method for quantitating peripheral blood B cells is described which utilizes anti-heavy chain specific antibody attached to polyacrylamide beads. The method has the advantages of ease of performance, of utilizing reagents which are commercially available and routine phase microscopy. In addition, the reagents are stable for prolonged periods of time and only small amounts are required. Utilizing this assay, the following percentages of B cells have been found in normals: IgG 6.3 +/- 0.6; IgM 4.3 +/- 0.5; IgA 4.0 +/- 0.5. The polyacrylamide beads may be phatocytized allowed recognition of certain phagocytic mononuclear cells.

To investigate B-cell function in acquired immune deficiency syndrome (AIDS), we immunized a group of patients with AIDS with pneumococcal polysaccharide (tetradecavalent) and protein (keyhole-limpet hemocyanin) antigens. Antibody responses were determined three to four weeks after immunization. Compared with controls, patients with AIDS had significantly lower geometric mean antibody levels to polysaccharide before and after immunization. Levels before and after immunization were frequently below a level thought to correlate with protection. Patients with AIDS also had a significant reduction in their primary antibody response to the protein antigens. The results of these studies indicate that AIDS is associated with an acquired B-cell as well as T-cell immunodeficiency. It is suggested that future studies should consider the evaluation of passive antibody in the prevention of infection and/or prevention of progressive immunodeficiency.

To delineate the normal function of purine nucleoside phosphorylase and to understand the pathogenesis of the immune dysfunction associated with deficiency of this enzyme, we studied purine metabolism in a patient deficient in purine nucleoside phosphorylase, her erythrocytes and cultured fibroblasts. She exhibited severe hypouricemia and hypouricosuria but excreted excessive amounts of purines in her urine, the major components of which were inosine and guanosine. Her urine also contained deoxyinosine, deoxyguanosine and uric acid 9-N riboside. The patient's erythrocytes but not her cultured fibroblasts contained increased concentrations of phosphoribosylpyrophosphate and inosine. The metabolic abnormalities resembled those in the erythrocytes of patients with the Lesch-Nyhan syndrome. Purine nucleoside phosphorylase is a necessary component of the major, if not the sole, pathway for the conversion of purine nucleosides and nucleotides to uric acid. The increased intracellular concentrations of inosine may, by inhibiting adenosine deaminase, be related to the immunologic dysfunction.

Four of 13 patients followed with chronic granulomatous disease (CGD) developed biopsy-proven Aspergillus pneumonia. Two patients died of disseminated aspergillosis despite intensive treatment; delays in diagnosis appear to have been a major contributing cause. Two patients survived two episodes each of Aspergillus pneumonia, three and six years apart. At 12 and 18 years of age, both are well and active, although their chest X-rays show residual scarring and pulmonary function tests indicate obstructive lung disease. These cases demonstrate that in patients with CGD, 1) multiple episodes of Aspergillus pneumonia can occur; 2) effective immunity to the organism does not develop after infection; and 3) some survivors of Aspergillus pneumonia experience only minimal morbidity.

Lymphotoxin (LT) and tumor necrosis factor (TNF) are cytokines with many common biologic effects including antiviral activity and induction of fever and the acute phase response; despite common effects, they are molecularly distinct. Because neonates are unduly susceptible to viral infection and frequently fail to mount a febrile response to infection, we hypothesized that neonatal cells would produce less LT and TNF than adult cells. We analyzed LT and TNF production by blood mononuclear cells and purified T cells using Northern blot analysis to detect specific messenger ribonucleic acid and specific assays to detect LT and TNF protein in culture supernatants. Compared to LT, TNF messenger ribonucleic acid and protein were produced more rapidly both by total mononuclear cells and by T cells in response to mitogen stimulation. Although there was intersubject variability, adult and neonatal mononuclear cells and T cells (n = 6) produced similar amounts of LT and TNF messenger ribonucleic acid and protein with similar kinetics. In experiments with phytohemagglutinin-stimulated mononuclear cells from ten additional subjects, supernatant LT was somewhat greater in neonatal cultures (neonatal = 62.8 +/- 60.5, adult = 13.2 +/- 10.7 units/ml, p less than 0.05), and TNF was somewhat greater in adult cultures (neonatal = 708 +/- 429, adult = 1987 +/- 392 pg/ml, p less than 0.01) at 24 h; results at 48 h and 72 h were similar. Thus, neonatal MC produced as much or more LT than did adult MC. Although the decreased production of TNF by neonatal MC was statistically significant, these cells did produce substantial amounts of this cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)

A spontaneously occurring antibasement membrane antibody has been further characterised according to antigenic specificity, immunoglobulin class, and tissue localisation using immunofluorescent and immunoelectron microscopic techniques. The autoantibody reacted with the basement membrane of kidney tubules, Bowman's capsule, and the epithelial portion of ileum but not with the basement membrane of skin, cornea, glomerulus, or oesophagus. It also reacted with bile canaliculi, sarcolemmal sheath, and salivary duct. On electron microscopy the antibody was distributed along the basement membrane of Bowman's capsule and renal tubules. Some reactivity against collagen was observed. Antibody activity was found in both IgG and IgM fractions. In immunodeficiency disorders, the autoantibody was found only in patients with selective IgA deficiency.

Peripheral blood mononuclear cells from patients with acquired immune deficiency syndrome proliferate poorly after stimulation with soluble mitogens. The present study was undertaken to assess the relative contributions of T lymphocytes and of plastic adherent mononuclear cells to the impaired mononuclear cell responses. We employed a four-step separation procedure including terminal depletion using a monocyte-specific monoclonal antibody (61D3) to derive populations of highly purified T cells from patients and from normal subjects. Highly purified T cells proliferated poorly in response to phytohemagglutinin and pokeweed mitogen. The addition of autologous adherent cells to highly purified T cells markedly improved mitogen-driven proliferation in all subjects; however, mononuclear cells from patients with AIDS responded less well than normals (P less than or equal to 0.01) for both phytohemagglutinin and pokeweed. Allogeneic normal adherent cells fully restored both phytohemagglutinin and pokeweed responses in normal highly purified T cells. Adherent cells from patients were comparable to normal adherent cells in phytohemagglutinin-driven proliferation but performed significantly less well when pokeweed was used to stimulate normal highly purified T-cell responders (4308 cpm after coculture with patients' adherent cells vs 8244 cpm after coculture with allogeneic normal adherent cells; P = 0.05). Similarly, when patient's highly purified T cells were stimulated with pokeweed mitogen, control adherent cells functioned substantially better than patient adherent cells (1198 cpm for allogeneic patient adherent cells vs 2324 cpm for normal adherent cells; P = 0.05). Although the addition of normal adherent cells to patients' highly purified T cells significantly improved pokeweed mitogen responses, these values did not reach normal. Suppression by patients adherent cells was not demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Fifty-five patients with squamous cell carcinoma of the head and neck and esophagus were evaluated prior to irradiation and thymosin fraction 5 therapy. Immunity prior to treatment, as measured by total lymphocyte count, E and EAC rosettes, lymphocyte stimulation with phytohemagglutinin (PHA) and in mixed leukocyte culture (MLC) with allogeneic cells, delayed hypersensitivity skin tests, and quantitative serum immunoglobulins, was comparable and normal in the 40 control patients and in the 15 thymosin-treated patients. After irradiation, significant depression (P less than 0.01) was demonstrated in cellular immunity in both groups of patients with decreased T- and B-cell numbers and depressed phytohemagglutinin and MLC stimulation. Six months after irradiation, our preliminary results suggest that the thymosin-treated patients may be reversing their immunosuppression by a return of MLC function and positivity of delayed hypersensitivity skin tests. The ultimate effect of thymosin on disease control and survival remains uncertain.

Two children with adenosine deaminase (ADA) deficiency and combined immunodeficiency disease were given parenteral deoxycytidine in order to reverse the severe T-cell immunodeficiency associated with this disease. One patient received a total of three courses of parenteral deoxycytidine. On two occasions deoxycytidine (50 mg/kg/day) was infused intravenously continuously for 2 weeks. During one of the infusions she received the deoxycytidine deaminase inhibitor tetrahydrouridine (THU). Steady-state levels of plasma deoxycytidine increased 4-fold with THU. RBC dCTP/dATP increased more than 10-fold after 48 hr of deoxycytidine infusion. Immunologic studies following the intravenous infusion of deoxycytidine showed transient improvement in T-cell immunity. The third course of deoxycytidine (50 mg/kg/day) was administered subcutaneously during a 10-hr night-time infusion. After 6 and 12 weeks of nightly subcutaneous infusions, there was minimal improvement in the in vitro immunologic studies and no clinical improvement. The second patient received a single 2-week course of continuous intravenous deoxycytidine (50 mg/kg/day) following which there was no significant change in T-cell immunity. This study defines some of the pharmacologic parameters of human deoxycytidine metabolism and suggests that some patients with ADA deficiency may respond to deoxycytidine therapy with improvement in T-cell-mediated immunity, although the changes are small and the effect on clinical status appears to be limited.

In 8 of 18 homosexual men with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) treated with intravenous co-trimoxazole (trimethoprim-sulphamethoxazole) apparent drug-related complications developed during the course of acute therapy. A symptom complex of fevers and increasing malaise, often with nausea and headaches, developed usually after 9 days of therapy at a daily dosage of 20 mg/kg of trimethoprim and 100 mg/kg of sulphamethoxazole. These symptoms were associated with a diffuse erythematous maculopapular eruption and peripheral cytopenias. A similar picture was noted in two children with suspected AIDS-associated PCP. The high frequency of adverse reactions to co-trimoxazole therapy for PCP seems to be characteristic of AIDS patients.

Seventy percent of pneumococci isolated from the middle-ear cavity of infants and children with acute otitis media were of one of the seven serotypes 1, 3, 6, 14, 18, 19, or 23. The immunological response in the serum and middle-ear fluid from otitis media caused by one of these serotypes was studied in 61 children by using either indirect hemagglutination or indirect fluorescent antibody tests, or both. Twenty-six of the patients had pneumococcal antibody present in the acute serum and 28 had it in the convalescent serum by at least one method. Thirteen of the 49 middle-ear fluids examined had antibody by the indirect fluorescent antibody technique. Serum pneumococcal antibody was found to reside predominantly in the immunoglobulin G or immunoglobulin M classes, whereas pneumococcal antibody with middle-ear fluid was found to be distributed equally among all three classes. Approximately 25% of the patients (16 of 61) had a positive immune response to their infection as evidenced by increased levels of pneumococcal antibody in the convalescent serum. The percentage of patients responding immunologically increased with age: 12% of infants less than 12 months showed a significant response, whereas 48% of children over 24 months responded.

Reconstitution of cell-mediated immunity was achieved in a 5-month old female infant with severe combined immunodeficiency by fetal thymus transplant given simultaneously with two units of transfer factor. Thymus was obtained from a 15-week gestational age male fetus, and the two units of transfer factor from the lymphocytes of 500 ml of peripheral blood. Three weeks after transplantation, two nel HL-A antigens were detected on the infant's lymphocytes, one of which was present in the mother of the thymus donor; at the same time, some of the infant's own HL-A antigens disappeared. Thereafter, the percent of rosette-forming cells (T-cells) increased and the in vitro response to phytohemagglutinin and allogeneic lymphocytes became normal, and delayed skin tests became positive. Karyotyping of peripheral blood lymphocytes posttransplantation reveals an XY (male) pattern. These results suggest lymphocyte re-population as a result of the thymus-transfer factor therapy. Five months after transplantation, the patient has normal cellular immunity but persistent hypogammaglobulinemia. She is free of infection and growing normally on gammaglobulin injections.

Unique laboratory abnormalities, found in pediatric patients with clinical features of immunodeficiency, led to the original observation that a syndrome of acquired immunodeficiency (AIDS) was also occurring in pediatric populations. Initial observations which demonstrated the nonspecific findings of polyclonal hypergammaglobulinemia and T-cell deficiency were followed by confirmatory findings when testing for the AIDS retrovirus became available. In the pediatric population availability of antibody testing and viral isolation became critical in differentiating primary immunodeficiency disorders which involved both the B- and T-cell systems from AIDS associated with retrovirus infection. At this time based upon clinical, epidemiologic, immunologic, and serologic studies, the syndrome of pediatric AIDS can be distinguished from other primary and secondary pediatric immunodeficiency disorders.

Severe combined immunodeficiency disease (SCID) in patients with adenosine deaminase (ADA) deficiency is thought to result from increased levels of purine metabolites. We attempted to immunosuppress a patient with ADA deficiency and SCID using a continuous infusion of deoxyadenosine to obtain engraftment of a T cell-depleted haplocompatible parental bone marrow graft. Before administering the drug in vivo, we investigated hematopoietic colony formation in two children with ADA deficiency (including the potential recipient), the obligate heterozygote donor (father), and normal controls using deoxyadenosine and erythro-9-(2-hydroxy-3-nanyl)adenosine (EHNA), and inhibitor of ADA. Deoxyadenosine alone in concentrations as high as 100 microM had no significant affect on erythroid (BFU-E) or myeloid (CFU-c) colony formation. However, in the presence of EHNA there was a significant reduction in BFU-E and CFU-c growth in all subjects and controls. Increasing doses of deoxyadenosine were given to one patient with ADA deficiency and SCID as a continuous 24-hr intravenous infusion. We found that there was a linear relationship between the dose administered and the plasma level; however, doses greater than 100 mg/day were required to increase erythrocyte dATP levels. We were able to raise intracellular dATP levels to more than three times baseline with doses of deoxyadenosine of 200 mg/day. However, there were no significant effects on the absolute lymphocyte counts or the lymphocyte responses to mitogen or alloantigen, and the haploidentical marrow failed to engraft. Our results suggest that the bone marrow of ADA-deficient patients is normal with respect to standard colony formation, that inhibitors of ADA do not adequately model the deficient state, and that the immunodeficiency in ADA deficiency is not proportionately related to either the deoxyadenosine or dATP levels, both of which were significantly elevated at the time of transplantation.

Patients with Hodgkin's disease (HD) have a high risk of overwhelming pneumococcal infections after splenectomy. Previous studies have shown that HD patients given polyvalent pneumococcal polysaccharide (PPS) vaccine after immunosuppressive therapy have a suboptimum antibody response. This study shows significant antibody response in HD patients to PPS vaccine given before radiation and chemotherapy. The same response was obtained whether the vaccine was given before or after splenectomy.

The influence of recombinant human transforming growth factor-beta (rHuTGF-beta) on B-cell function and antigen-specific T-cell responses in vitro was investigated. The addition of 0.1 ng/ml of rHuTGF-beta to cultures of peripheral blood mononuclear cells (PBMC) stimulated with tetanus toxoid resulted in a 50% inhibition of the PBMC proliferative response as determined by [3H]thymidine incorporation. Further, rHuTGF-beta at 0.37 ng/ml caused a greater than 50% reduction in the number of immunoglobulin G-secreting cells among PBMC induced by pokeweed mitogen. rHuTGF-beta also inhibited the generation of allospecific cytotoxic T lymphocytes (CTL) in the mixed-lymphocyte reaction but had no effect on the cytolytic function of CTL generated in the absence of exogenous HuTGF-beta. The results indicate additional immunoregulatory activities for HuTGF-beta and suggest that this factor may play an important role in the regulation of the antigen-dependent immune response.

The major limitation of mismatched bone marrow transplantation is fatal graft versus host disease (GVHD). We processed haplotype-identical parental marrow with soybean agglutinin (SBA), sheep erythrocytes (SRBC), and neuraminidase-treated SRBC (N-SRBC) to enrich for marrow stem cells and remove mature T cells. Nine patients with severe combined immunodeficiency disease (SCID) who lacked histocompatible donors received these SBA-negative, SRBC-negative, N-SRBC-negative marrow transplants (0.5-5.0 X 10(8) cells/kg). Seven of the nine patients (78%) had documented T-lymphocyte engraftment based on HLA typing and/or chromosomal analysis. Six patients showed evidence of B-cell immunity on the basis of increased immunoglobulin levels, isohemagglutinins, and/or HLA-DR typing of non-T cells. Three patients received marrow ablative chemotherapy pretransplant for maternal-fetal GVHD; neutrophil engraftment occurred between 9 and 17 days posttransplantation, erythrocytes engrafted within 3-4 weeks of transplantation, and platelet recovery was seen between day 17 and day 49 following the transplants. No immunosuppression was given prophylactically posttransplant. Three patients had no GVHD, two had transient rash and/or fever, and two developed mild focal (stage I) chronic cutaneous GVHD. Of the seven who engrafted, five (71%) are alive and clinically well without GVHD 18-35 months posttransplant. These data demonstrate that SBA- and SRBC/N-SRBC-treated haploidentical marrow transplantation results in functional lymphocyte engraftment in SCID without significant GVHD, and can be used for some patients who otherwise would have no hope for survival.

The classification of the pediatric acquired immunodeficiency syndrome (AIDS) is based on epidemiologic, immunologic, and virologic data. Persons at risk include mothers who use intravenous drugs, infants who have received blood transfusions from subjects with risk factors, patients receiving factor VIII therapy, and infants born to heterosexual mothers with bisexual husbands. A distinct immunologic phenotype, rarely seen in other immunodeficiency disorders, is associated with pediatric AIDS consisting of polyclonal hypergammaglobulinemia and T-cell immunodeficiency. Detection of antibody to the AIDS retrovirus or isolation of virus are essential in establishing a diagnosis. During early infancy, viral isolation is essential as passive transfer of material IgG may occur. Primary immunodeficiency diseases, in particular adenosine deaminase and purine nucleoside phosphorylase deficiency, should be excluded. A diagnosis of pediatric AIDS may be established in a patient who has a risk factor associated with AIDS, polyclonal hypergammaglobulinemia, T-cell immunodeficiency, and antibody to the AIDS retrovirus or isolation of virus.

Homosexual men with Kaposi sarcoma, lymphadenopathy syndrome, opportunistic infection, and nonhomosexual traditional Kaposi sarcoma were evaluated for B cell, T cell, and complement immunity and compared to normal controls and homosexual controls. No significant immunologic abnormalities were found in the traditional Kaposi group. All homosexual groups, including the homosexual controls, had a significant decrease in the helper/suppressor cell ratio. Functional abnormalities of T-cell immunity were observed in the homosexual Kaposi sarcoma, lymphadenopathy syndrome, and opportunistic infection groups. Significant elevations of IgG, IgM, IgA, and IgE were found in the lymphadenopathy group, while only IgG and IgA were elevated in the Kaposi sarcoma group. C3, C4, and immune complexes were normal, while total hemolytic complement activity was increased in the Kaposi sarcoma and lymphadenopathy syndrome groups.

An enzyme-linked immunosorbent assay has been developed to detect serum immunoglobulin G and M antibodies against pneumococcal polysaccharide antigens. Parameters affecting the specificity and sensitivity of the assay are described. A vigorous antibody response involving both the immunoglobulin G and M classes was demonstrated after pneumococcal polysaccharide immunization in normal adults. Studies with this enzyme-linked immunosorbent assay technique will allow further understanding of the biology of the primary and secondary immune response to Streptococcus pneumoniae in normals as well as in those persons most susceptible to infection with that organism.

Human immunodeficiency virus (HIV) infection is associated with abnormalities of both T-cell and B-cell immunity in patients with acquired immunodeficiency syndrome (AIDS). Previous studies demonstrated deficient production of the cytokines interleukin-1 (IL-1), interleukin-2 (IL-2), and gamma interferon (IFN-gamma). Tumor necrosis factor alpha and tumor necrosis factor beta have not been previously investigated in AIDS. In this study we demonstrate that peripheral blood mononuclear cells from patients with HIV infection who have either AIDS-related complex or acquired immunodeficiency syndrome are deficient in the production of tumor necrosis factor alpha and tumor necrosis factor beta. These cytokines, derived predominantly from monocytes or lymphocytes, respectively, function as immunoregulatory, antitumor, and antiinfective proteins. A deficiency in their production may therefore be responsible for many of the complications associated with HIV infection in patients with AIDS-related complex or acquired immunodeficiency syndrome.

Clinical and laboratory findings in 138 children seen during a ten-year period with a positive antinuclear antibody (ANA) test were reviewed. Two thirds (91 of 138) of the patients had specific autoimmune or rheumatic diseases, including systemic lupus erythematosus (n = 37), juvenile rheumatoid arthritis (n = 33), Sjögren's syndrome (n = 9), mixed connective tissue disease (n = 7), dermatomyositis (n = 3), and discoid lupus (n = 2). Another 27 patients had symptoms of autoimmune disease but did not fit criteria for specific disorders. Nine patients with IgA deficiency had a positive ANA test but did not have symptomatic autoimmune disease. Ten children had a positive ANA test in association with infections, mainly viral, and one had leukemia. Because most children with a positive ANA test had readily diagnosable autoimmune disorders, pediatric patients with a positive ANA on repeated testing should undergo clinical and laboratory studies for autoimmune or rheumatic disease.