Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray.

In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8(+) T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild-type allele (20-30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5-10%) demonstrated in pretransplant blood DNA. This may be responsible for the patient's unusual immunological phenotype compared to classical interleukin (IL)-7Rα deficiency. Disseminated VZV was controlled with anti-viral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients.

Robust T cell responses to aspergillosis in chronic granulomatous disease: implications for immunotherapy.

Chronic granulomatous disease (CGD) patients are highly susceptible to invasive aspergillosis and might benefit from aspergillus-specific T cell immunotherapy, which has shown promise in treating those with known T cell defects such as haematopoietic stem cell transplant (HSCT) recipients. But whether such T cell defects contribute to increased risks for aspergillus infection in CGD is unclear. Hence, we set out to characterize the aspergillus-specific T cell response in CGD. In murine CGD models and in patients with CGD we showed that the CD4(+) T cell responses to aspergillus were unimpaired: aspergillus-specific T cell frequencies were even elevated in CGD mice (P < 0·01) and humans (P = 0·02), compared to their healthy counterparts. CD4-depleted murine models suggested that the role of T cells might be redundant because resistance to aspergillus infection was conserved in CD4(+) T cell-depleted mice, similar to wild-type animals. In contrast, mice depleted of neutrophils alone or neutrophils and CD4(+) T cells developed clinical and pathological evidence of pulmonary aspergillosis and increased mortality (P < 0·05 compared to non-depleted animals). Our findings that T cells in CGD have a robust aspergillus CD4(+) T cell response suggest that CD4(+) T cell-based immunotherapy for this disease is unlikely to be beneficial.

Association of maternal drug use during pregnancy with maternal HIV culture positivity and perinatal HIV transmission.

OBJECTIVE: To evaluate the relationship of drug use with maternal HIV culture positivity at delivery and perinatal HIV transmission. DESIGN: Multicenter prospective cohort study. SETTING: Obstetric and pediatric clinics in five cities in the United States. PARTICIPANTS: Five hundred and thirty HIV-infected pregnant women and their infants. MAIN OUTCOME MEASURES: Multivariate logistic regression was used to evaluate the association of 'hard drug' use (one or more of the following: cocaine, heroin/opiates, methadone, injecting drug use) assessed by self-report and urine toxicology with positive maternal HIV culture at delivery and perinatal HIV transmission. RESULTS: Forty-two per cent of women used hard drugs during pregnancy. Increased probability of a positive maternal delivery HIV culture was significantly associated with prenatal hard drug use [odds ratio (OR), 3.08] and maternal cocaine use (OR, 2.98) among HIV-infected women with > 29% CD4+ lymphocytes. After adjusting for maternal culture positivity at delivery, CD4+ lymphocyte percentage and gestational age, significantly greater transmission risk was observed with hard drug use among women with membrane rupture > 4 h. CONCLUSIONS: On the basis of self-report and urine toxicology, overall maternal hard drug use and cocaine use in the WITS cohort were associated with maternal HIV culture positivity at delivery, and maternal hard drug use was associated with perinatal transmission.

The immunogenicity of Haemophilus influenzae type b conjugate vaccines in children born to human immunodeficiency virus-infected women. Women and Infants Transmission Study Group.

BACKGROUND: Immunocompromise caused by HIV-1 infection increases the importance of receipt of routine childhood vaccines to prevent infections such as invasive Haemophilus influenzae type B (Hib) disease. The objectives of the study were to evaluate the immunogenicity of Hib conjugate vaccines among HIV-infected children according to clinical and immunologic disease progression as well as viral load. METHODS: The concentration of antibody to polyribosylribitol phosphate (PRP) was measured at approximately 9 and 24 months of age in plasma specimens from children of HIV-infected women enrolled in the Women and Infants Transmission Study. RESULTS: Among 227 children (35 HIV-infected, 192 uninfected) at the 9-month study visit who were known to have received age-appropriate immunization with CRM197 mutant Corynebacterium diphtheriae protein-conjugated Hib vaccine, geometric mean antibody concentrations were lower among HIV-infected children (1.64 microg/ml) than among uninfected children (2.70 microg/ml), although the difference was not statistically significant. Anti-PRP antibody concentrations did not vary significantly among these HIV-infected children with predominantly mild-moderate disease progression according to clinical category, immunologic stage or viral load (P > or = 0.48). The proportion of children with antibody concentrations > or = 1.0 microg/ml did not vary significantly according to HIV infection status (73% uninfected, 74% infected) or, if infected, clinical or immunologic disease progression or viral load. Similar results were obtained among 127 children (17 HIV-infected, 110 uninfected) eligible for analysis at the 24-month study visit. Changes in antibody concentrations over time (between 9 and 24 months of age) did not differ significantly among 10 HIV-infected as compared with 72 uninfected children (P=0.81). CONCLUSIONS: These results suggest that HIV-infected children with predominantly mild-moderate disease progression respond reasonably well in terms of a quantitative antibody response to Hib conjugate vaccines during the first 2 years of life. Research to further characterize the immune response to Hib conjugate vaccines and to further delineate the "durability" of anti-PRP antibody concentrations beyond 2 years of life should be pursued.

Mother-to-child transmission of the human immunodeficiency virus in Texas.

BACKGROUND: The Pediatric Spectrum of HIV Diseases (PSD) project has been collecting data on HIV-exposed children in Texas since 1989. These data have now been analyzed to describe mother-to-child transmission in Texas and to provide much needed information on the magnitude of the pediatric HIV epidemic in the state. METHODS: We examined trends in the numbers of perinatally exposed children and perinatally acquired cases of HIV in the Texas PSD cohort. We calculated transmission rates and relative risks for 656 children born from January, 1995, to July, 1998, that received all or part of the ACTG 076 regimen. RESULTS: Only a small proportion (38%) of pairs of an HIV-infected mother and her HIV-exposed child received the full AIDS Clinical Trial Group 076 (ACTG 076) regimen; only 73% of the mothers received at least some prenatal care. In recent years, however, the numbers of perinatally exposed children and perinatally acquired cases of HIV have decreased in Texas. Univariate analyses showed that a reduction in the vertical transmission of HIV was associated with receipt of a full ACTG 076 regimen, receipt of a partial ACTG 076 regimen and residence in Dallas County. CONCLUSIONS: Findings identify a gap in meeting the health care needs of pregnant HIV-infected women and suggest missed opportunities to prevent mother-to-child transmission of HIV. At the same time this study confirms progress in prevention efforts to reduce mother-to-child transmission of HIV in Texas.

Organ-specific manifestations of HIV disease in children.

The clinical manifestations of HIV disease in children affect multiple organ systems. The severity of each manifestation varies by organ system and can be related in many cases to multifactorial causes, namely HIV replication in affected tissue, concomitant opportunistic infection of the organ, effect of concurrent immunodeficiency or autoimmune mechanisms on the organ, or adverse end-organ drug effect (primary HIV therapy or prophylaxis regimens). More information is needed to understand the pathogenesis of the systemic effect of HIV on different organ systems, especially the CNS. Most clinicians hope that advances in therapeutic interventions for primary HIV will halt the progression of the organ-specific manifestations that have been outlined in this article, but such potent therapies will probably have their own unique and new effects on HIV-infected organ systems. Vigilance for organ-specific manifestations in the era of HAART is imperative to provide the best clinical outcome for HIV-infected children.

Case management of HIV-infected children in Missouri.

The early referral of HIV-exposed children and their mothers to coordinated medical and social services has become increasingly important. In July 1989, the Missouri Department of Health initiated the Service Coordination Program to provide individualized referral (case management) for Missouri residents who were reported to have acquired immunodeficiency syndrome (AIDS) or HIV infection. The purpose of the Service Coordination Program is to assist persons in accessing medical and social services. The authors describe the characteristics of the 36 children (18 enrolled in the Service Coordination Program, and 18 not enrolled) reported to the Missouri Department of Health through September 1992. Although more detailed evaluations are necessary, preliminary data suggest that opportunities for early intervention may be facilitated by the Service Coordination Program if the child's HIV status is recognized early.

Role of placental cytokines and inflammation in vertical transmission of HIV infection.

In light of new evidence suggesting that maternal human immunodeficiency virus (HIV) infection produces at least a three-fold increase in the number of early spontaneous abortions, it is important to search for factors that may predispose to fetal wastage. Immunological factors are thought to play an important role in permitting the HLA-disparate fetus to continue to term, despite powerful maternal immune forces capable of rejection. In the context of a heightened incidence of spontaneous abortion in HIV infection, evidence is now accumulating that implicates an imbalance in immune factors in contributing to this fetal loss. Soluble immune factors, such as cytokines, have been suggested as contributing agents to recurrent spontaneous abortions. Inflammatory cytokines-interleukin 1beta, interleukin 6 and tumor necrosis factor alpha-have been measured in isolated placental trophoblastic cells in HIV-infected and non-infected pregnant women in an attempt to explore this hypothesis. These inflammatory cytokines and their messenger RNAs were significantly elevated before and after stimulation in HIV-infected women, supporting the belief that HIV-infected women present their fetuses a milieu of imbalanced immune factors capable of contributing to immunological rejection. In addition, these elevated inflammatory cytokine levels may contribute to HIV disease progression in fetuses by virtue of activation of HIV gene transcription factors similar to what has been demonstrated in in vitro systems. We therefore propose that HIV infection in pregnant women produces an altered state of certain soluble immune factors, which in concert with other immune factor abnormalities, such as loss of immune selection in the fetal thymus, predisposes the fetus to advanced HIV infection and possible spontaneous abortion.

Early spontaneous abortions and fetal thymic abnormalities in maternal-to-fetal HIV infection.

The thymus is thought to play a major role in the immunopathogenesis of human immunodeficiency virus (HIV) infection, particularly in maternal-to-fetal HIV transmission. Characteristic lesions of the HIV-infected thymus include a prominent CD4+ CD8+ T lymphocyte depletion at the corticomedullary junction, the region of the thymus where immune selection occurs. At least threefold excess early spontaneous abortions were noted in a cohort of 124 HIV-infected pregnant women. In these 13 abortuses a very high rate (54%) of HIV vertical transmission was documented, with the thymus gland particularly affected. It is possible that the thymic insult in HIV-infected fetuses contributes to immune rejection of the fetus, possibly by an imbalance of maternal and fetal T1- and T2-type cytokines, known to be important in HIV disease progression. We propose, therefore, that the early spontaneous abortions occurring in HIV-infected pregnant women are due, at least in part, to abnormal immune forces created by HIV infection of the thymus.

Immunization prevalence rates for infants in a large urban center: Houston/Harris County, 1993.

Immunization prevalence rates in Houston/Harris County for children 18 to 24 months were determined by a prospective immunization survey conducted from January through May 1993. Rates for immunization series were very low for 2-year old children regardless of infant gender, maternal age, maternal education, or immunization provider (public verus private). African-American infants had the lowest likelihood of completing their immunization series. Infants who had received their first immunization within the scheduled time frame were most likely to complete the series. More than 57% of caregivers could not state accurately the immunization status of their children. Barriers to immunizations perceived by caregivers were identified as medical barriers, vaccine cost, and transportation. New goals for infant immunization delivery have been established by the national Comprehensive Children's Immunization Initiative. To meet these goals, large urban centers like Houston/Harris County must use resources through both public and private sectors, ie, networked, confidential immunization tracking system; enhanced and sustained educational efforts; and expansion of vaccine availability.

Parental perceptions of barriers to childhood immunization: results of focus groups conducted in an urban population.

The current US immunization rates for 2 year olds are approximately half of the goal set for the year 2000. Research studies have focused primarily on the perception of health care providers in the identification of barriers and benefits to childhood immunization. While health care providers are an important part of the immunization delivery process, the perceptions of parents are also important. In this study, qualitative methods were used to explore perceived parental barriers to childhood immunization delivery. Twelve focus groups comprising White, African-American, Hispanic, urban and non-urban people were conducted at a variety of sites, including clinics, churches, schools and work sites. The results indicated that time off from work, access to well-child care and difficulty understanding the complexity of the immunization schedule were seen as barriers to adhering to an immunization schedule. Participants emphasized problems in taking time off from work to get immunizations, sometimes without pay, and expressed fears that doing so would jeopardize promotions and raises. While some of the parental perceptions were similar to those identified in studies of health care providers in the literature, many were not. This study emphasizes the importance of gathering information from parents as well as from health care providers.

Sexual abuse of children: intersection with the HIV epidemic.

OBJECTIVE: Sexual transmission of human immunodeficiency virus (HIV) is the predominant risk exposure among adolescents and adults reported with HIV infection and acquired immunodeficiency syndrome (AIDS). Although perinatal transmission accounts for the majority of HIV infection in children, there have been reports of HIV transmission through sexual abuse of children. We characterized children <13 years of age who may have acquired HIV infection through sexual abuse. METHODS: All reports by state and local health departments to the national HIV/AIDS surveillance system of children with HIV infection not AIDS (n = 1507) and AIDS (n = 7629) through December 1996 were reviewed for history of sexual abuse. Information was ascertained from data recorded on the case report form as well as investigations of children with no risk for HIV infection reported or identified on initial investigation. For children with a possible history of sexual abuse, additional data were collected, including how sexual abuse was diagnosed; characteristics of the perpetrator(s) (ie, HIV status and HIV risks); and other possible risk factors for the child's HIV infection. RESULTS: Of 9136 children reported with HIV or AIDS, 26 were sexually abused with confirmed (n = 17) or suspected (n = 9) exposure to HIV infection; mean age of these children at diagnosis of HIV infection was 8.8 years (range, 3 to 12 years). There were 14 females and 3 males who had confirmed sexual exposure to an adult male perpetrator at risk for or infected with HIV; of these, 14 had no other risk for HIV infection, and 3 had multiple risks for HIV infection (ie, through sexual abuse, perinatal exposure, and physical abuse through drug injection). The other 9 children (8 females, 1 male) had no other risk factors for HIV infection and were suspected to have been infected through sexual abuse, but the identity, HIV risk, or HIV status of all the perpetrator(s) was not known. All cases of sexual abuse had been reported to local children's protective agencies. Sexual abuse was established on the basis of physician diagnosis or physical examination (n = 20), child disclosure (n = 15), previous or concurrent noncongenital sexually transmitted disease (n = 9), and for confirmed cases, criminal prosecution of the HIV-infected or at-risk perpetrator (n = 8). For the 17 children with confirmed sexual exposure to HIV infection, 19 male perpetrators were identified who were either known to be HIV infected (n = 18) or had risk factors for HIV infection (n = 17), most of whom were a parent or relative. CONCLUSIONS: These 26 cases highlight the tragic intersection of child sexual abuse and the HIV epidemic. Although the number of reported cases of sexual transmission of HIV infection among children is small, it is a minimum estimate based on population-based surveillance and is an important and likely underrecognized public health problem. Health care providers should consider sexual abuse as a possible means of HIV transmission, particularly among children whose mothers are HIV-antibody negative and also among older HIV-infected children. The intersection of child abuse with the HIV epidemic highlights the critical need for clinicians and public health professionals to be aware of the risk for HIV transmission among children who have been sexually abused, and of guidelines for HIV testing among sexually abused children, and to evaluate and report such cases.

Acquired immune deficiency, myelodysplasia, and acute nonlymphocytic leukemia associated with monosomy 7 and t(3;3) (q21;q26) in a child with Langerhans cell histiocytosis.

A case of therapy-related myelodysplasia followed by acute nonlymphocytic leukemia in a 5-year-old child successfully treated for diffuse Langerhans cell histiocytosis is described. A syndrome of severe cell-mediated immune deficiency and persistent Epstein-Barr virus (EBV) infection coincided with the evolution of myelodysplasia. Specific abnormalities of chromosomes number 7 and 3 were associated with the onset of myelodysplasia and acute nonlymphocytic leukemia and are believed to be linked to the patient's immune dysfunction and compromised ability to contain viral infection.

Monoclonal anti-T cell (T12) antibody treatment of graft-versus-host disease in severe combined immunodeficiency: targeting of antibody and activation of complement on CD8+ cytotoxic T cell surfaces.

We report a 6-month-old male child with severe combined immunodeficiency who received an unirradiated blood transfusion and developed acute, severe graft-versus-host disease (GVHD), for which he received monoclonal anti-T cell (anti-T12) antibody treatment. The GVHD was manifested by a confluent maculopapular rash and increased liver function tests and was documented by skin biopsy. Separation of peripheral blood mononuclear cells forming rosettes with sheep red blood cells revealed engrafted T cells having the nonrelated HLA type of the blood donor. The patient was treated with intravenous monoclonal anti-T12 in a dose of 0.3 mg/kg/day for 5 days. An in vivo effect of the anti-T12 was suggested by clinical improvement of his skin rash and return of the liver transaminases to the normal range. Moreover, human complement components, activated C3 and C4, were detected by fluorescence microscopy on the surfaces of the engrafted CD8+ lymphocytes on the skin biopsy specimens. Also, with a biotin-avadin assay, the presence of the anti-T12 was detected on these same cells. These studies document not only the in vivo targeting of monoclonal anti-T12 antibody to cytotoxic T cells producing GVHD but also the activation of complement on these cells.

Excess intrauterine fetal demise associated with maternal human immunodeficiency virus infection.

A prospective study of transplacental transmission of human immunodeficiency virus (HIV) showed an increased rate of spontaneous fetal demise in HIV-seropositive mothers: 14 losses in 124 pregnancies. HIV was detected in placental and fetal tissues in 7 of 14 by in situ hybridization. The proportion of fetal infection far exceeded the transmission rate of 13% in liveborn babies. No association was seen between fetal transmission and a maternal history of drug abuse or coinfections; mothers with AIDS more often had fetal loss associated with HIV transmission than did asymptomatic mothers. In affected fetuses, HIV was detected in many tissues and was associated with thymic pathology. This suggests that maternal HIV infection increases the risk for pregnancy loss associated with HIV transmission. The possibility that HIV may be fetotoxic, that thymic dysfunction may interfere with pregnancy progression, or that the intrauterine milieu in HIV-seropositive pregnancies may be unfavorable (or a combination of factors) should be considered.

Early detection of HIV in infants: aspects of design and analysis for diagnostic test studies.

OBJECTIVE: To review investigations on the early detection of HIV infection in infants to determine adherence to traditional methods of study design and analysis for evaluating new laboratory tests. DATA SOURCES: A National Library of Medicine (MEDLINE) search was conducted to identify such investigations through 1993. Cited references in identified manuscripts were also considered. The search was restricted to investigations of human subjects and those published in the English language. STUDY SELECTION: Final inclusion criteria included (1) report of the age and human immunodeficiency virus (HIV) infection status of the subjects at the time of the diagnostic testing, and (2) presentation of data allowing confirmation of presented analyses and additional analyses. DATA EXTRACTION: Criteria for judging the investigations included (1) whether the criteria used to determine the positive and negative test results were defined; (2) whether the necessary sample size for the study was calculated; (3) whether the patients studied were representative of the patients to whom the test would be applied; (4) whether a gold standard evaluation was performed; (5) whether the outcomes included in the analyses were independent; (6) whether the test characteristics were properly analyzed; and, (7) whether confidence intervals were presented. DATA SYNTHESIS: An informative presentation of a diagnostic test should include as a minimum the seven criteria listed above. Only 21 of 36 (58%) of the studies incorporated at least three of the criteria. CONCLUSIONS: There is a wide variation in the manner in which investigations of diagnostic tests are conducted and the results reported. Increased awareness and use of standard study designs and analyses will allow the application of metanalyses. Such analyses will help guide the direction taken for finding and establishing early diagnostic procedures for HIV infection at birth or during infancy.

Maternal and infant factors predicting disease progression in human immunodeficiency virus type 1-infected infants. Women and Infants Transmission Study Group.

BACKGROUND: Infants with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection have widely variable courses. Previous studies showed that a number of maternal and infant factors, when analyzed separately, are associated with infant HIV-1 disease progression. In this study, clincal, virologic, and immunologic characteristics in the mothers and infants were examined together to determine the predictors of disease progression by 18 months of age and the associations with rapid progression during the first 6 months of life. METHODS: One hundred twenty-two HIV-1-infected women whose infants were HIV-1 infected were identified from the Women and Infants Transmission Study (WITS) cohort. WITS is a longitudinal natural history study of perinatal HIV-1 infection carried out in 6 sites in the continental United States and in Puerto Rico. The women were enrolled during pregnancy and their infants were enrolled at the time of delivery and followed prospectively by a standardized protocol. Virologic and immunologic studies were performed in laboratories certified by National Institutes of Health-sponsored quality assurance programs. Maternal factors in pregnancy were used as potential predictors of infant disease progression (progression to Centers for Disease Control and Prevention [CDC] Clinical Class C disease or death by 18 months of age) or as correlates of progression at <6 months of age. Infant factors defined during the first 6 months of life were used as potential predictors of progression during 6 to 18 months of age and as correlates of progression at <6 months of age. RESULTS: Progression by 18 months of age occurred in 32% of infants and by 6 months of age in 15%. Maternal characteristics that, by univariate analysis, were significant predictors of infant disease progression by 18 months of age were elevated viral load, depressed CD4(+)%, and depressed vitamin A. CD8(+)%, CD8(+) activation markers, zidovudine (ZDV) use, hard drug use, and gestational age at delivery were not. When examined in a combined multivariate analysis of maternal characteristics, only vitamin A concentration independently predicted infant progression. Infant characteristics during the first 6 months of life that, by univariate analysis, were associated with disease progression included elevated mean viral load at 1 to 6 months of age, depressed CD4(+)%, CDC Clinical Disease Category B, and growth delay. Early HIV-1 culture positivity (<48 hours), CD8(+)%, CD8(+) activation markers, and ZDV use during the first month of life did not predict progression. Multivariate analysis of infant characteristics showed that the only independent predictors were progression to CDC Category B by 6 months of age (odds ratio [OR], 5.80) and mean viral load from 1 to 6 months of age (OR, 1.99). The final combined maternal and infant analysis included the significant maternal and infant characteristics in a multivariate analysis. It showed that factors independently predicting infant progression by 18 months of age were progression to CDC Category B by 6 months of age (OR, 5.80) and elevated mean HIV-1 RNA copy number at 1 to 6 months of age (OR, 1.99). The characteristics associated with rapid progression to CDC Category C disease or death by 6 months of age were also examined. The only maternal characteristic associated with progression by 6 months in multivariate analysis was low maternal CD4(+)%. The infant characteristics associated with progression by 6 months of age in multivariate analysis were depressed mean CD4(+)% from birth through 2 months and the presence of lymphadenopathy, hepatomegaly, or splenomegaly by 3 months. Infant ZDV use was not assocciated with rapid progression. CONCLUSION: The strongest predictors of progression by 18 months are the presence of moderate clinical symptoms and elevated RNA copy number in the infants in the first 6 months of life. In contrast, progression by 6 months is associated with maternal and infant immun

Objective measures of allergic disease in children with human immunodeficiency virus infection.

BACKGROUND: Available information suggests that IgE levels are elevated in adults infected with human immunodeficiency virus (HIV), and that increased IgE levels correlate with allergic disease, with decreased CD4 counts, and with a poor prognosis. Data with respect to these factors in children are scant. OBJECTIVE: We investigated whether serum IgE levels are elevated in children with HIV and, if so, whether the serum IgE level correlates with the degree of immunodeficiency and/or objective indicators of allergic disease. METHODS: Serum IgE levels, CD4 counts, absolute eosinophil counts, and immediate hypersensitivity skin test (IHST) results were collected from 43 children with symptomatic HIV infection (mean age 7.2 years). Associations between serum IgE levels, CD4 counts, and eosinophil counts were investigated by multiple stepwise linear regression analysis. Data were stratified according to IHST positivity, and analysis of variance was used to compare mean values for age, CD4 counts, IgE levels, and eosinophil counts between the two groups. RESULTS: Serum IgE values were elevated more than 2 SDs above control age-matched mean values in 17 of 43 patients (40%). IHST results were positive in 12 of 43 patients (28%). CD4 counts were less than 200/mm3 in 17 of 43 patients (40%). Stepwise linear regression failed to demonstrate any correlation between serum IgE levels and either CD4 or eosinophil counts. With data divided into two groups according to IHST results (positive vs negative), analysis of variance failed to reveal significant differences between means for patient age, CD4 counts, IgE levels, or eosinophil counts. CONCLUSIONS: Our findings confirm that serum IgE levels are increased in children infected with HIV, just as in adults. However, an elevated serum IgE level did not correlate with allergic disease as measured by IHST results and eosinophil counts, nor with the degree of immune dysfunction as approximated by CD4 counts. The mechanism and significance of elevated serum IgE levels remain unclear in children with HIV, and warrant further investigation.

Tumors of smooth-muscle origin in HIV-infected children.

We report the occurrence of multiple leiomyomata and leiomyosarcomata in three children with the acquired immunodeficiency syndrome. The children were infected with human immunodeficiency virus as infants (one perinatally and two through transfusions) and each was profoundly immunosuppressed (absolute CD4 cell count, less than 75/mm3). They experienced multiple infections prior to the diagnosis of neoplasms at ages 4, 5, and 8 years, respectively. The tumors in each case were mainly involving the lungs and gastrointestinal tract. The smooth-muscle origin of the tumors was proved by light and electron microscopy and immunohistochemical staining for muscle-specific actin and desmin. Leiomyomata and leiomyosarcomata are rare tumors in childhood, suggesting a nonrandom association of tumors of smooth-muscle origin and the acquired immunodeficiency syndrome. We postulate that human immunodeficiency virus infection may play a direct or indirect role in tumor formation.