Efficacy and tolerability of 16% subcutaneous immunoglobulin compared with 20% subcutaneous immunoglobulin in primary antibody deficiency.

Multiple subcutaneous immunoglobulin (SCIG) products are available to treat primary antibody deficiency (PAD). The efficacy and tolerability of 16% SCIG (Vivaglobin(®) ) was compared with 20% SCIG (Hizentra(®) ) in PAD subjects. The study was a prospective, single-centre, open-label study of PAD subjects transitioning Vivaglobin to equivalent Hizentra doses, rounded to the nearest vial size. Comparisons included immunoglobulin (Ig)G levels; tetanus, varicella and Streptococcus pneumoniae titres; adverse events (AEs), annual infection rate and quality of life during 8 weeks of Vivaglobin and 24 weeks of Hizentra. Thirty-two subjects (aged 2-75 years) participated. Rounding to the nearest Hizentra vial size resulted in a 12·8% (± 2·9%) increase in SCIG dose. Median immunoglobulin (Ig)G level following 8 weeks of Vivaglobin was similar to 24 weeks of Hizentra (1050 versus 1035 mg/dl, respectively; P = 0·77). Both products had similar protective titres to tetanus, varicella and serotypes of S. pneumoniae, which were variable but well above protective levels. After 12 weeks of Hizentra, subjects reported fewer local site reactions compared with Vivaglobin. Switching products resulted in increased systemic AEs in some subjects but, overall, not significantly higher than during Vivaglobin treatment. Average infusion time decreased from 104·7 min (3·3 sites) with Vivaglobin to 70·7 min (2·2 sites) with Hizentra (P = 0·0005). Acute serious bacterial infections were similar. Treatment satisfaction was superior with Hizentra. Hizentra and Vivaglobin have similar pharmacokinetics and efficacy. Although transition to a different SCIG product initially increased AEs, Hizentra is well tolerated and can be infused more rapidly and with fewer sites compared to Vivaglobin.

Subcutaneous immunoglobulin replacement therapy with Hizentra, the first 20% SCIG preparation: a practical approach.

To reduce the risk of infection in adults and children with primary immunodeficiencies, replacement therapy with IgG, which can be administered to patients intravenously or subcutaneously, is required. Although intravenous administration of IgG (IVIG) has been the therapy of choice in the US and widely used in Europe for many years, subcutaneous administration of IgG (SCIG) has recently gained considerable acceptance among patients and doctors. SCIG therapy achieves high and stable serum IgG levels, is well tolerated, and can be self-administered. Hizentra (IgPro20; CSL Behring, Berne, Switzerland) is the first, ready-to-use 20% liquid preparation of human IgG specifically formulated for subcutaneous infusions. The high concentration (20%) might allow shorter infusion times due to smaller infusion volumes, with potential improvement in the convenience of SCIG therapy. Hizentra is well tolerated and has been shown to protect adult and pediatric primary immunodeficiency patients against serious bacterial infections. In addition, it is easy to handle and can be stored at a temperature up to 25°C. In summary, Hizentra is an advance in the field of immunoglobulin replacement therapy, which might offer benefits for home therapy patients.

FOXP3 expression following bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning.

The objective of this study is to determine if immune reconstitution of FOXP3+ T regulatory cells correlates with clinical improvement of IPEX syndrome following allogeneic hematopoietic stem cell transplant. An 8-months-old male infant with a mutation in the polyadenylation site of FOXP3 gene, absence of FOXP3 protein expression and clinical manifestations of IPEX syndrome, including eczema, colitis, failure to thrive, TPN requirement, and elevated serum IgE, underwent matched unrelated hematopoietic stem cell transplant. After reduced-intensity conditioning with alemtuzumab followed by fludarabine and melphalan the patient's neutrophils engrafted day +15 and platelets day +29. Patient was a full donor chimera day +28 and +60. Intracellular FOXP3 protein expression in CD4+ T cells was absent pre-HSCT. After transplantation, percentage CD4+ T cells expressing FOXP3+CD25 bright phenotype quickly increased from 4.5 (day +29) to 23% (day +90) and continued in this trend. Foxp3 mRNA expression confirmed flow cytometry data. Serum IgE levels decreased from 5,000 IU/ml pre-transplant to 6 IU/ml on day +90, eczema resolved, and secretory diarrhea and feeding intolerance improved. T regulatory cell reconstitution is evident soon after HSCT following reduced-intensity conditioning correlating with development of full donor chimerism. Increased FOXP3 expression correlates with correction of clinical and laboratory manifestations of IPEX syndrome providing direct evidence that HSCT is a curative procedure for this disorder.

Abacavir pharmacokinetics during chronic therapy in HIV-1-infected adolescents and young adults.

The pharmacokinetics of abacavir and its metabolites were investigated in 30 human immunodeficiency virus (HIV)-infected adolescents and young adults 13-25 years of age, equally divided into two groups: <18 years of age and >or=18 years of age. All the subjects received the recommended adult dose of 300 mg twice daily. The area under the plasma concentration-time curve (AUC) and half-life of abacavir did not differ significantly between the age groups or by gender or race, and there were only modest associations of age with apparent abacavir clearance and with volume of distribution. There were no significant correlations of carboxylate or glucuronide metabolite levels with age or gender, although glucuronide AUC was higher in Hispanic subjects than in African-American subjects. Zidovudine and lamivudine concentration profiles were also similar in the two age groups. A novel aspect of the study included an assessment of intracellular carbovir, zidovudine, and lamivudine triphosphate levels, and these were found to be similar in the two age-based groups. Overall, these findings suggest that current recommendations relating to adult dosages are appropriate for adolescents and young adults.

Clinical assessment of medication adherence among HIV-infected children: examination of the Treatment Interview Protocol (TIP).

This paper presents findings of a multi-site study designed to document: (1) caregivers' regimen knowledge; (2) barriers to adherence; and (3) the relationships between adherence, regimen knowledge and barriers. Fifty-one predominantly female, African American parents and caregivers of HIV-infected children completed the Treatment Interview Protocol (TIP), a brief, structured interview designed to assess regimen knowledge and barriers to adherence. TIP data were compared to information obtained from medical records and pharmacy refill histories. Forty-nine per cent of children were considered adherent, defined as > or = 90% refill rate, which was significantly associated with virologic response. Significant regimen knowledge deficits were observed among caregivers, and inaccurate identification of prescribed medications was significantly associated with adherence. Caregivers identified 21 barriers to adherence, and poor adherence was significantly related to the number of barriers reported. Results indicate that the TIP is a successful tool for identifying regimen knowledge, potential adherence barriers and adherence problems. Results suggest that the TIP could be integrated into clinical practice as a quick, effective tool to identify poor adherers and guide interventions and treatment decision making.

Human lymphocyte proliferation responses following primary immunization with rabies vaccine as neoantigen.

Evaluation of the T-cell immune response following primary antigenic challenge with a neoantigen is a critical aspect of assessment of the cellular immune response. While many antigens can be used to accurately assess in vitro T-cell proliferation to a recall antigen, only a few neoantigens have been tested for their capacities to measure T-cell responses in vitro to a primary immunization. Rabies vaccination is an excellent candidate for the testing of T-cell proliferation responses to a primary immunization because few individuals have been exposed to rabies virus antigens. In the present study 14 rabies vaccine-naïve, healthy adult volunteers were immunized against rabies virus, and T-cell proliferation and antibody responses were measured before and after vaccination. Optimal lymphocyte proliferation to soluble rabies virus antigen occurred after 8 days in culture. The average level of uptake of tritiated thymidine postimmunization was 29,620 +/- 4,448 cpm, whereas preimmunization levels were 12,660 +/- 3,448 cpm (P = 0.002). All individuals showed increases in rabies virus antibody titers from <0.05 to 5.59 +/- 1.64 IU/ml. The degree of proliferation to tetanus toxoid as a recall antigen was similar to the response to rabies virus antigen among the cohort. Due to high levels of preimmunization proliferation, four subjects failed to demonstrate a twofold increase in response to rabies virus antigen. The high levels of T-cell responses may be due to a viral superantigen effect in some individuals. Rabies vaccination offers a safe and effective means for measurement of both T- and B-cell immune responses to a neoantigen in healthy and immune suppressed individuals.

Natural history of neonatal herpes simplex virus infections in the acyclovir era.

OBJECTIVE: During the 2 decades in which effective antiviral therapies have been available for neonatal herpes simplex virus (HSV) disease, changes have been documented not only in the outcomes of infected infants, but also in the natural history of the disease itself. Numerous studies previously have reported that early institution of antiviral therapy is beneficial to the outcome of the disease. The objective of this study was to provide an update of neonatal HSV disease to identify means by which future improvements in the management of HSV-infected neonates can be made. DESIGN/METHODS: Neonates enrolled in 2 studies of parenteral acyclovir for the treatment of neonatal HSV disease provided the data source. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted the studies between 1981 and 1997. A total of 186 patients are summarized, all of whom were treated with acyclovir. Demographic and clinical characteristics of these patients are reported. RESULTS: Comparisons between patients treated in the periods between 1981-1988 and 1989-1997 according to extent of disease revealed that the mean time between the onset of disease symptoms and initiation of therapy has not changed significantly from the early 1980s to the late 1990s. Of all patients evaluated, 40% had fetal scalp monitors during the delivery process. A significant minority of patients did not have skin vesicles at the time of their presentation and did not develop them during the acute HSV disease (39% of patients with disseminated disease; 32% of patients with central nervous system [CNS] disease; and 17% of patients with skin, eye, and/or mouth disease). Among patients with CNS disease, mortality was associated with prematurity. Among patients with disseminated HSV disease treated with acyclovir at 30 mg/kg/d, mortality was associated with aspartate transaminase elevations of >/=10 times the upper limit of normal at the time of initiation of acyclovir therapy. Mortality was also associated with lethargy at initiation of antiviral therapy for patients with disseminated disease. Patients' morbidity status was associated with the extent of disease (skin, eye, and/or mouth disease vs CNS vs disseminated). For those patients with CNS disease, morbidity was also associated with seizures at initiation of antiviral therapy. CONCLUSION: Data presented in the current comparison of neonatal HSV disease over the 2 periods (1981-1988 vs 1989-1997) demonstrate that no progress has been made in decreasing the interval between onset of HSV symptoms and initiation of antiviral therapy. Additional strides in the improvement of disease outcome may occur only if the interval between onset of symptoms and initiation of therapy is shortened. The means by which this will be accomplished lie in increased consideration of neonatal HSV infections in acutely ill infants. Specific data and recommendations to facilitate this goal are contained within.

Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections.

OBJECTIVE: The objective of this investigation was to establish the safety of high-dose (HD) acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD acyclovir was also assessed. PARTICIPANTS: Infants who were

Long-term virologic and immunologic responses in human immunodeficiency virus type 1-infected children treated with indinavir, zidovudine, and lamivudine.

Virologic and immunologic responses were examined for 33 human immunodeficiency virus (HIV)-infected children who participated for > or = 96 weeks in a phase 1/2 protocol of 16 weeks of indinavir monotherapy, followed by the addition of zidovudine and lamivudine. At week 96, a median increase of 199 CD4+ T cells/microL and a median decrease of 0.74 log(10) HIV RNA copies/mL were observed. The relationship between control of viral replication and CD4) T cell count was examined. Patients were categorized into 3 response groups on the basis of duration and extent of control of viral replication. Of 21 children with a transient decrease in virus load of > or = 0.7 log(10) HIV RNA copies/mL from baseline, 7 experienced sustained increases in CD4+, CD4+ CD45RA+, and CD4+ CD45RO+ T cell counts. CD4+ CD45RA+ (naive) T cells were the major contributor to CD4+ T cell expansion. Continued long-term immunologic benefit may be experienced by a subset of children, despite only transient virologic suppression.

Human immunodeficiency virus type 1 protease genotype predicts immune and viral responses to combination therapy with protease inhibitors (PIs) in PI-naive patients.

Protease genotype, as a variable in outcome to combination therapy for human immunodeficiency virus (HIV) type 1 infection, was evaluated among protease inhibitor-naive children and adolescents who had received extensive treatment with reverse-transcriptase inhibitors. After 24 weeks of combination therapy, 35% had viral and immune success (VSIS patients), 19% had viral and immune failure (VFIF patients), and 46% had viral failure but marked improvement in CD4 T cells (VFIS patients). Disease stage was the only pretherapy clinical variable associated with outcome (P=.02). Although reverse-transcriptase genotype was unrelated to outcome, pretherapy protease genotype was related significantly to therapy response (P=.005). Odds for immune or viral failure were 17.7 to 1 and 2.5 to 1, respectively, for protease genotype as a single variable. Protease genotype combined with disease stage and CD4 cell percentage predicted correct therapy response for 81% of patients (100% of VFIF, 78% of VSIS, and 75% of VFIS patiens). Naturally occurring amino acid polymorphisms in protease provide sensitive biomarkers for treatment response among inhibitor-naive patients with advanced HIV disease.

T-Cell receptor Vbeta repertoire CDR3 length diversity differs within CD45RA and CD45RO T-cell subsets in healthy and human immunodeficiency virus-infected children.

The T-cell receptor (TCR) CDR3 length heterogeneity is formed during recombination of individual Vbeta gene families. We hypothesized that CDR3 length diversity could be used to assess the fundamental differences within the TCR repertoire of CD45RA and CD45RO T-cell subpopulations. By using PCR-based spectratyping, nested primers for all 24 human Vbeta families were developed to amplify CDR3 lengths in immunomagnetically selected CD45RA and CD45RO subsets within both CD4(+) and CD8(+) T-cell populations. Umbilical cord blood mononuclear cells or peripheral blood mononuclear cells obtained from healthy newborns, infants, and children, as well as human immunodeficiency virus (HIV)-infected children, were analyzed. All T-cell subsets from newborn and healthy children demonstrated a Gaussian distribution of CDR3 lengths in separated T-cell subsets. In contrast, HIV-infected children had a high proportion of predominant CDR3 lengths within both CD45RA and CD45RO T-cell subpopulations, most commonly in CD8(+) CD45RO T cells. Sharp differences in clonal dominance and size distributions were observed when cells were separated into CD45RA or CD45RO subpopulations. These differences were not apparent in unfractionated CD4(+) or CD8(+) T cells from HIV-infected subjects. Sequence analysis of predominant CDR3 lengths revealed oligoclonal expansion within individual Vbeta families. Analysis of the CDR3 length diversity within CD45RA and CD45RO T cells provides a more accurate measure of disturbances in the TCR repertoire than analysis of unfractionated CD4 and CD8 T cells.

Genetically and epidemiologically related "non-syncytium-inducing" isolates of HIV-1 display heterogeneous growth patterns in macrophages.

The objective of this study was to identify phenotypic parameters that could distinguish among seemingly homogeneous non-syncytium-inducing (NSI) viruses and that might provide a surrogate marker for clinical progression in pediatric human immunodeficiency virus type 1 (HIV-1) infection. We undertook a pilot analysis of 15 independent HIV-1 isolates collected prospectively from two mothers and their four children who displayed a spectrum of disease stages ranging from CDC categories A1 to C3. Viruses were evaluated for their ability to replicate in primary cells (including monocyte-derived macrophages [MDM]) and cell lines, for their co-receptor preference and for genetic features of the V3 hypervariable domain of env. Virtually all isolates displayed NSI phenotypes that were restricted in their capacity to replicate in cell lines and displayed V3 loops with uniformly low net positive charges. NSI viruses from two symptomatic children and one mother were macrophage-tropic, whereas NSI isolates from two asymptomatic children were unable to replicate in MDM and were designated primary lymphotropic viruses. Only one isolate was syncytium-inducing (SI), replicated in a variety of cell lines and in MDM, used multiple co-receptors, and was dual tropic, rather than a mixture of T-cell tropic and M-tropic viruses, as assessed by genetic analysis. Phenotypic heterogeneity among NSI viruses is revealed in the ability of isolates to replicate in MDM. This characteristic is related to disease stage and provides a potentially new in vitro criterion to distinguish among NSI isolates that is unlinked to other surrogate markers.

Immunoreconstitution after ritonavir therapy in children with human immunodeficiency virus infection involves multiple lymphocyte lineages.

OBJECTIVE: To evaluate lymphocyte reconstitution after protease inhibitor therapy in children with human immunodeficiency virus (HIV) infection. STUDY DESIGN: Forty-four HIV-infected children receiving ritonavir monotherapy followed by the addition of zidovudine and didanosine were evaluated during a phase I/II clinical trial. The cohort had a median age of 6.8 years and advanced disease (57% Centers for Disease Control and Prevention stage C, 73% immune stage 3) and was naive to protease inhibitor therapy. RESULTS: After 4 weeks of therapy, there was a significant increase in CD4(+) and CD8(+) T cells. CD4(+) T cells continued to increase, whereas CD8(+) T cells returned to baseline by 24 weeks. Unexpectedly, there was a significant increase in B cells. Changes in CD4(+) T-cell subsets revealed an initial increase in CD4(+) CD45RO T cells followed by a sustained increase in CD4(+) CD45RA T cells. Children <6 years of age had the highest increase in all lymphocyte populations. Significant improvement in CD4(+) T-cell counts was observed even in those children whose viral burden returned to pre-therapy levels. CONCLUSIONS: Early increases in lymphocytes after ritonavir therapy are a result of recirculation, as shown by increases in B cells and CD4(+) CD45RO and CD8(+) T cells. Children exhibited a high potential to reconstitute CD4(+) CD45RA T cells even with advanced disease and incomplete viral suppression.

Expression of CCR5 increases during monocyte differentiation and directly mediates macrophage susceptibility to infection by human immunodeficiency virus type 1.

The stage of differentiation and the lineage of CD4+ cells profoundly affect their susceptibility to infection by human immunodeficiency virus type 1 (HIV-1). While CD4(+) T lymphocytes in patients are readily susceptible to HIV-1 infection, peripheral blood monocytes are relatively resistant during acute or early infection, even though monocytes also express CD4 and viral strains with macrophage (M)-tropic phenotypes predominate. CCR5, the main coreceptor for M-tropic viruses, clearly contributes to the ability of CD4+ T cells to be infected. To determine whether low levels of CCR5 expression account for the block in infection of monocytes, we examined primary monocyte lineage cells during differentiation. Culturing of blood monocytes for 5 days led to an increase in the mean number of CCR5-positive cells from <20% of monocytes to >80% of monocyte-derived macrophages (MDM). Levels of CCR5 expression per monocyte were generally lower than those on MDM, perhaps below a minimum threshold level necessary for efficient infection. Productive infection may be restricted to the small subset of monocytes that express relatively high levels of CCR5. Steady-state CCR5 mRNA levels also increased four- to fivefold during MDM differentiation. Infection of MDM by M-tropic HIV-1JRFL resulted in >10-fold-higher levels of p24, and MDM harbored >30-fold more HIV-1 DNA copies than monocytes. In the presence of the CCR5-specific monoclonal antibody (MAb) 2D7, virus production and cellular levels of HIV-1 DNA were decreased by >80% in MDM, indicating a block in viral entry. There was a direct association between levels of CCR5 and differentiation of monocytes to macrophages. Levels of CCR5 were related to monocyte resistance and macrophage susceptibility to infection because infection by the M-tropic strain HIV-1JRFL could be blocked by MAb 2D7. These results provide direct evidence that CCR5 functions as a coreceptor for HIV-1 infection of primary macrophages.

SLE nephritis is associated with an oligoclonal expansion of intrarenal T cells.

Autoimmune systemic lupus erythematosus (SLE) nephritis is characterized by the influx of mononuclear inflammatory cell infiltrates within the glomeruli and renal interstitium. To evaluate the possibility that intrarenal T cells result from the expansion of lymphocytes using limited T-cell receptor (TCR) genes, we analyzed the TCR Vbeta gene expression among infiltrating lymphocytes in renal tissue compared with simultaneous peripheral blood lymphocytes of four children with new-onset SLE nephritis. The TCR Vbeta gene expression in peripheral blood T cells from patients with SLE nephritis, when compared with normal controls, showed no preferential expansion or deletion of select Vbeta gene families. In contrast, when paired peripheral blood and renal tissue were analyzed, intrarenal lymphocytes in SLE nephritis demonstrated evidence of expansion of select Vbeta gene families. Sequence analysis of the V(D)J joining regions of the TCRbeta with the expanded families demonstrated a striking oligoclonality. These observations suggest that infiltrating T cells within renal tissue may use TCR Vbeta genes targeted toward nephritogenic antigens.

Multilocular thymic cysts in children with human immunodeficiency virus infection: clinical and pathologic aspects.

BACKGROUND: Children with human immunodeficiency virus (HIV) infection have an increased susceptibility to severe and unusual infections, malignancies, and disorders characterized by abnormal lymphoproliferation (e.g., lymphoid interstitial pneumonitis). We report a novel disease entity associated with pediatric HIV infection that is characterized by massive enlargement of the thymus as a result of lymphoid hyperplasia and multicystic changes. METHODS: Eight patients with HIV infection and cystic enlargement of the thymus are subject of this report. The status of their HIV disease and its clinical and radiologic manifestations at the time of diagnosis of the mediastinal mass are described. Tissue specimens were obtained from six patients and examined by microscopy and immunohistochemistry. The specimens were also evaluated for the evidence of HIV and Epstein-Barr virus by in situ hybridization. RESULTS: Patients were between 2.1 and 12.1 years of age, with CD4+ cell counts between 102 and 733 cells/mm3. In all eight cases an anterior mediastinal mass was discovered incidentally on radiography of the chest, and computed tomography of the chest revealed a multicystic appearance. Histologic examination demonstrated distortion of the thymic architecture by focal cystic changes, lymphoid follicular hyperplasia, diffuse plasmacytosis, and multinucleated giant cells. In situ hybridization revealed HIV particles on the surface of follicular dendritic cells. Further, results of in situ hybridization for EBV were positive in lymphoid cells from biopsy samples of four patients. The patients were followed between 8 months and 4.8 years. In five patients the mass either decreased in size or resolved completely. CONCLUSIONS: We describe a series of children with HIV infection and multilocular thymic cysts. We hypothesize that aberrant immunoregulation in these HIV-infected children leads to follicular hyperplasia and multicystic changes in the thymus, causing massive enlargement. EBV infection might also contribute to the pathogenesis of this process. Because none of our patients had symptoms from the mass, and there was no evidence of malignancy in the examined biopsy samples, it seems prudent to manage such children with careful follow-up examinations.

Zidovudine administered to women infected with human immunodeficiency virus type 1 and to their neonates reduces pediatric infection independent of an effect on levels of maternal virus.

OBJECTIVE: To determine whether zidovudine, administered to reduce vertical transmission of human immunodeficiency virus type 1 (HIV-1), impacts the level of maternal viral DNA within the lymphocytes of infected pregnant women. STUDY DESIGN: A prospective, nonrandomized study of 42 HIV-1 infected pregnant women. Nineteen women received zidovudine therapy to reduce HIV-1 perinatal transmission, and 23 were untreated. HIV-1 DNA was determined by polymerase chain reaction amplification of lymphocyte DNA from maternal blood samples obtained at the time of delivery. Treated and untreated, transmitting and nontransmitting groups were compared for clinical, virologic, and immunologic parameters with at test or a Fisher Exact Test, and for copies of HIV-1 DNA per 10(6) CD4+ T cells with a Mann-Whitney rank sum test. RESULTS: Untreated pregnant women who transmitted HIV-1 to their infants had tower CD4+ T-cell counts and a greater degree of immune complex dissociated p24 antigenemia than did the untreated nontransmitting group (p < 0.01) but did not differ significantly with respect to age, race, or mode of delivery. The level of HIV-1 proviral DNA within lymphocytes was significantly greater in the untreated transmitting group than in the nontransmitting mothers (p = 0.003). Zidovudine treatment resulted in a 78% decrease in maternal transmission (p = 0.017). However, there was not a significant difference in DNA copy numbers in CD4+ T cells in the treated compared with the untreated groups. CONCLUSION: Zidovudine reduces HIV-1 maternal transmission independent of its effect on the level of the maternal peripheral blood proviral load.

Antiphospholipid antibodies in pediatric lupus nephritis.

Antiphospholipid antibodies (aPL) of various isotypes are known to occur in systemic lupus erythematosus (SLE), but the significance of this finding in the pediatric population remains unclear. Our aim was to determine whether children with lupus nephritis have an increased risk of thrombosis and whether antiphosphatidylserine (APS) or antiphosphatidylinositol (API) antibodies were predictive of thrombotic complications. Thirty-six children (27 girls/9 boys; 44% black) with SLE nephritis (WHO II, 1; WHO III, 7; WHO IV, 21; WHO V, 7) were evaluated for antiphosphatidylserine, antiphosphatidylinositol, and anticardiolipin immunoglobulin (Ig) G and IgM isotypes, using a modified solid-phase enzyme-linked immunoassay (ELISA). Twenty-four patients (67%) had at least one positive aPL. Longitudinal data on 26 patients showed fluctuations in the degree of positivity. Eight patients experienced thrombotic complications, with equal distribution between arterial and venous events. Other clinical manifestations included thrombocytopenia in seven patients (19%), hemolytic anemia (44%), lupus anticoagulant (6%) and false-positive Venereal Disease Research Laboratory (VDRL) test results (11%). Comparisons between those with and without a thrombotic event showed no detectable difference in the incidence of aPL positivity between the two groups. We conclude that neither APS, API, nor anticardiolipin (ACL) activity was predictive of thrombotic complications in our subset of patients with lupus nephritis.