The effect of testosterone replacement treatment on immunological features of patients with Klinefelter's syndrome

Although the effects of androgen deficiency in the immune system have long been appreciated, little is known about the immunological features of patients with Klinefelter's syndrome (KS). On the other hand, interest in androgens as a possible treatment for some autoimmune diseases is growing. In the present study, some immunological parameters were evaluated in 26 patients with KS prior to androgen replacement treatment (ART) and the results were compared with those in 19 healthy control subjects. Patients were then treated with testosterone for 6 months and the pre- and post-treatment findings were compared. Serum levels of IgG, IgA, IgM, C3c and C4 were measured by nephelometry and lymphocyte subsets and CD4+/CD8+ ratios were examined by flow cytometry. IL-2 and IL-4 levels were measured by ELISA. Pretreatment levels of the serum IgA, IgG, IgM, IL-2 and IL-4 of the patients were higher than those of the controls and were all decreased significantly following ART. The pretreatment absolute numbers and percentages of CD3+, CD4+, CD19+ cells and CD4+/CD8+ ratios of patients with KS were higher than those of the controls and were all decreased with ART. Percentages of CD8+ cells were increased significantly, while C3 and C4 levels were both significantly decreased after ART. It is concluded that the lack of testosterone in patients with KS enhances cellular and humoral immunity and that ART may suppress this.     

Persistent parvovirus B19 infections in immunocompromised children

Immunocompromised patients have been shown to suffer from prolonged viral infections often without detectable immune response. Here chronic infections with low virus levels can be frequently observed. In these patients viral DNA can be detected over long periods by polymerase chain reaction (PCR). In this study parvovirus B19 presence was assessed by PCR, immunoblot and enzyme-linked immunosorbent assay in sera from children with mainly oncological and hematological diseases. In 45% of sera B19 DNA was observed. Of the children 25% had IgG antibodies to viral protein 1 and 2 (VP1/2) and 15% to nonstructural protein 1 (NS1). In 6% of children IgM antibodies to VP1/2 were detected. These results indicate that the number of children with immune response to B19 proteins is distinctly lower than the number of children with B19 DNA. Transfusions of blood products might have been a possible route for B19 infection. Establishment and maintenance of a persistent parvovirus B19 infection with or without immune response are enhanced in the analyzed immunocompromised children in comparison with immunocompetent children. A persistence of B19 DNA was demonstrated up to 10 months in patients sera. Received: 22 September 1997     

Humoral and cellular immunity in children with Mycoplasma pneumoniae infection: a 1-year prospective study

To determine whether children have persistent abnormalities in cellular and humoral immunity development after acute Mycoplasma pneumoniae infection, serum immunoglobulin G (IgG), IgA, IgM, and IgE levels and lymphocyte phenotypes were determined. There were no changes in the levels of IgG, IgM, IgA, or CD4+ or CD19+ lymphocytes that were measured in M. pneumoniae-positive patients after 3 months or after 12 months, but there were increases in these in M. pneumoniae-negative patients. Serum IgE increased in M. pneumoniae-positive patients. We have shown alterations in immunity development after M. pneumoniae infection.     

Immunoglobulin levels in saliva in individuals with selective IgA deficiency: Compensatory IgM secretion and its correlation with HLA and susceptibility to infections

Total levels of IgA, IgM, and IgG were measured in unstimulated whole saliva and serum from 63 individuals with selective IgA deficiency. Values were compared with the incidence of upper respiratory tract infections, antibiotic treatments (necessitated by upper respiratory tract infections), and HLA antigens. A statistically significant increase in salivary IgM and IgG levels was noted in individuals with selective IgA deficiency compared to healthy normal individuals. Healthy individuals with selective IgA deficiency did not have increased concentrations of salivary IgM compared to infectious-prone patients. Nor was there any correlation found between proneness to infections and HLA antigens or between salivary IgM or IgG levels and HLA antigens in this patient material.     

Immunoglobulin deficiency in children with a sudden overwhelming infection.

BACKGROUND: A small percentage of previously healthy children develop a sudden overwhelming infection (SOI) that rapidly progresses and results in shock and, occasionally, death. Some of these children may have an undetected Ig deficiency. OBJECTIVE: The aim of this study was to evaluate the incidence of Ig deficiency in children with a SOI. METHODS: A case series study was conducted in a university hospital and included 18 children who either died in the emergency room or required admission to the pediatric intensive care unit secondary to a SOI. Two age-matched control groups included children hospitalized to regular floor beds with an infectious process (infected control group) or a noninfectious process (noninfected control group). Serum left from the initial blood draw, before fluid resuscitation, was collected and stored at -70 degrees C. Total IgG, IgG subclasses, IgM, and IgA were assayed by rate nephelometry in a blinded fashion. RESULTS: In the study group, one of six children under 1 year of age had low Ig levels in comparison with two of nine control patients. In those children over the age of 1 year, 8 of 12 patients (67%) had low Ig levels as compared with 2 of 19 controls (11%) by Fisher's exact test, P = .002. Of those patients with Ig deficiencies, three of eight had isolated IgG deficiency, two of eight had combined IgG and IgA deficiency, three of eight had combined IgG and IgM deficiency. CONCLUSIONS: Children over the age of 1 year who present with a SOI have a significantly higher incidence of Ig deficiencies compared with age-matched controls.     

A comparison of specific IgG antibody levels to the cell wall mannan of Candida albicans in normal individuals and in patients with primary antibody deficiency.

An enzyme-linked immunosorbent assay (ELISA) has been developed to measure specific IgG antibody to the polysaccharide, cell wall mannan of Candida albicans (mannan). The results were expressed as arbitrary units/ml, with an inter- and intra-assay coefficient of variation of 7-11%. In establishing normal ranges we found that specific IgG to the mannan increased with age, with 18% of healthy children aged 3-10, 48% of healthy children aged 11-19 and 76% of an adult donor population having specific IgG antibody to mannan (greater than 30 U/ml). We have compared these normal ranges, with a group of patients with primary antibody deficiency (PAD). None of the 23 patients with PAD, which included common variable immunodeficiency, IgG subclass deficiency, and selective IgA deficiency, had titres greater than 30 U/ml. The patients with PAD had significantly lower levels of specific IgG anti-mannan antibody (median 9 U/ml) compared to healthy children aged 11-19 (median 26 U/ml) or adults (median 58 U/ml) (p = less than 0.001) but not children aged 3-10, (median 1 U/ml) (p = 0.08).     

Detection of antibodies against viral capsid proteins of human herpesvirus 8 in AIDS-associated Kaposi’s sarcoma

 Sequences of a new herpesvirus with homology to gammaherpesvirinae were recently identified in AIDS-associated Kaposi’s sarcoma (KS). Subsequently this novel virus, called KS-associated virus (KSHV) or human herpesvirus (HHV) 8 was detected in classical KS and AIDS-associated body cavity based lymphomas by polymerase chain reaction. In this report major and minor capsid proteins of HHV-8 were molecularly cloned and produced as recombinant proteins in Escherichia coli. Sera from 69 HIV-1 infected patients with KS, 30 HIV-1 infected patients without KS and 106 control individuals were tested by enzyme-linked immunosorbent assay for anti-HHV-8 capsid IgM and IgG antibodies. Sera from four patients were tested over periods ranging from 18 months to 6 years. IgG antibodies directed against HHV-8 capsid antigens were detected in patients with AIDS-associated KS and in some AIDS patients without KS. Seroconversion with IgM and IgG antibodies directed against HHV-8 capsid proteins occurred more than 1 year prior to diagnosis of KS. In a considerable portion of KS patients no IgM or IgG antibodies against HHV-8 capsid proteins were detected. In these patients there was an inverse relationship between antibodies against HHV-8orf26 and the CD4/CD8 ratio, suggesting that the inconsistency of anti-HHV-8orf26 antibodies is due at least partly to an impaired immune response. No reactivity against HHV-8 capsid antigens was detected in the vast majority of sera from HIV-negative control individuals. Our findings indicate that a specific humoral immune response against capsid proteins is raised in HHV-8 infected individuals, and that anti-capsid antibodies can be used to diagnose HHV-8 infection. The correlation between occurrence of anti-HHV-8 antibodies and KS supports the hypothesis of a causative role of HHV-8. Received: 3 August 1996 / Accepted: 28 November 1996     

Hypogammaglobulinemia in a pediatric tertiary care setting

Hypogammaglobulinemia has been described as a secondary consequence of many disorders. It is also the seminal finding in many primary immune deficiencies. There are few studies examining the global etiologies of hypogammaglobulinemia. This study undertook a database discovery of all cases of laboratory-defined hypogammaglobulinemia identified in a large tertiary care pediatric hospital setting between August of 1990 until June of 2006. Eight thousand three hundred and four IgG levels were sent during that time frame. One thousand two hundred and ninety-five specimens from 680 individual patients exhibited hypogammaglobulinemia and these patients represent the study population. The majority of cases in whom an identifiable cause was found had pre-existing conditions and the IgG level was sent as part of a monitoring process. Of the 366 patients who had an IgG level obtained for diagnostic purposes, nearly half were found to have an immune deficiency. One hundred and seventy-two patients with an immune deficiency were identified. Seven percent of these had severe combined immune deficiency. Seventy-four percent of the immune deficient patients identified required active intervention with IVIG, bone marrow transplantation or other management (not including prophylactic antibiotics). Evaluating all patients with IgG levels less than half of the lower limit for age revealed 122 patients of whom 33% had a primary immune deficiency. This study provides a framework for considering causes of hypogammaglobulinemia. At the study institution, hypogammaglobulinemia was found most often as a secondary immune deficiency due to chemotherapy or from complex cardiac anomalies. The magnitude of the secondary hypogammaglobulinemia in a tertiary care setting requires public health consideration as these patients have an unknown risk of infection and an unknown risk of prolonged viral shedding; issues which could be important in epidemic settings.     

Diminished zinc plasma concentrations and alterations in the number of lymphocyte subpopulations in Down's syndrome patients

Alterations of plasma levels of zinc and in the immune system in Down's syndrome (DS) have been reported. These alterations have been associated with a high rate of infectious diseases, which represent the main cause of mortality in affected individuals. The objectives of this study were to determine plasma zinc levels and to evaluate the immune system in DS patients. Peripheral blood samples were obtained from 43 DS patients examined at the Unidad de Genética Médica, Universidad del Zulia in Maracaibo, Venezuela. Their mean age (+/- SD) was 2.3 +/- 2.0 years. As control group, 40 healthy children were studied (mean +/- SD 2.3 +/- 2.0 years). Karyotypes by a standard technique, the determination of plasma levels of zinc by atomic absorption spectrophotometry and the evaluation of the immune system by flow cytometry were carried out in the study groups. All DS patients had free trisomy 21. Significantly disminished zinc plasma levels, helper T lymphocyte (CD4) percentage, helper/cytotoxic (CD4/CD8) ratio and B-cells (CD19) were found in DS patients by matching with control group. An increase in CD8 was also found. No significative difference in the lymphocyte subpopulations between DS patients with disminished plasma levels of zinc and DS patients with normal zinc were found. These findings suggest that zinc deficiency is not the sole etiology involved in the disorders of immune system seen in DS patients. Other factors, such as thymic alterations and molecular abnormalities due to gene overexpression of loci located on chromosome 21 could be involved. Although, zinc supplementation is recommended in these patients with zinc deficiency, further studies with a double-blind, placebo versus zinc design are needed to evaluate the potentially beneficial effects of zinc treatment in DS patients.     

IgA1 is the major immunoglobulin component of immune complexes in the acquired immune deficiency syndrome

Compared to a panel of healthy controls, sera from 13 of 23 (57%) patients with the acquired immune deficiency syndrome (AIDS) were shown to have elevated levels of circulating immune complexes (CIC) containing IgA. Levels of IgG-containing CIC were increased in seven patients (30%); no patients had elevated levels of IgM-containing CIC. Additional experiments showed that in all instances in which IgG CIC were demonstrable, IgA was also present; however, IgA CIC could be found that did not contain IgG. The IgA in the CIC was restricted to the IgA1 subclass. These data suggest selective abnormalities of IgA regulation in AIDS and raise questions as to the role in this disease of the immunoglobulin isotype usually thought to possess different protective mechanisms from those attributed to other isotypes.     

Mannan-binding lectin may facilitate the clearance of circulating immune complexes--implications from a study on C2-deficient individuals

Deficiency of both mannan-binding lectin (MBL) and complement components C4 and C2 has been associated with increased risk of systemic lupus erythematosus (SLE). MBL can activate the complement system either through C4 and C2 or directly through C3. Circulating immune complexes (CICs) are believed to play a pathogenic role in SLE and MBL has been shown to bind certain forms of immunoglobulins, including IgM, IgG and IgA. Thus, MBL might promote CIC clearance. In order to evaluate this, six individuals with non-functional classical pathway due to the rare homozygous C2 deficiency were chosen, as the classical pathway is known to have a fundamental role in CIC clearance. Four of the six C2-deficient individuals had SLE, two of whom also had MBL deficiency. MBL serum levels and genotypes were compared with the serum levels of CICs, as measured by their content of kappa, lambda, IgM, IgA, IgG and C3 opsonization. The C2-deficient individuals had higher serum levels of CICs than 16 healthy controls (P < 0.0001). Furthermore, an inverse association was observed between MBL and CIC levels in the C2-deficient individuals, which was strongest for IgM-CICs (r = - 0.84, P = 0.037). Moreover, C3 opsonization of the CICs correlated positively with MBL levels in the C2-deficient individuals (r = 0.89, P = 0.017). In conclusion, individuals with C2 deficiency have increased levels of CICs and MBL may facilitate their clearance. Defective CIC clearance might partly explain the increased risk of SLE associated with low MBL.     

IgA and IgG Subclass Deficiency in a Poor Population in a Developing Country

The levels of IgG, IgG subclasses, IgM and IgA were determined in serum from 17 patients with IgA deficiency and severe or frequent infections, allergy and/or autoimmunity (median age 7 years, range 2–19), 11 healthy IgA-deficient adults and 35 controls (median age 7 years, range 2–19). In serum from all groups IgG, IgM and IgA antibodies were determined against β-lactoglobulin, E. coli O antigens and poliovirus type 1 antigen. In saliva of 15 IgA-deficient patients and 12 of the controls IgG, IgM and secretory component-carrying antibodies against E. coli O antigens and poliovirus type I were determined. The majority of the studied individuals lived under poor socio-economic conditions in Brazil, with consequent heavy microbial exposure. One IgA-deficient patient with rheumatoid arthritis also had IgG2 deficiency but no infectious problems. Four out of the 35 controls without any obvious infectious problems were found with IgA or IgG subclass deficiency. One of the 11 healthy IgA-deficient adults was low in the IgG2 subclass, one in IgGl and one in IgG3. Those with symptomatic IgA deficiency had significantly higher serum IgG than the controls, especially in the age group 6–11 years. This latter group also had significantly increased serum IgG 1 and IgG2 levels when compared with the age-matched controls. Salivary IgM antibodies to E. coli and poliovirus antigens were significantly higher among the symptomatic IgA-deficient individuals than among the controls. It is not clear at present whether these increased Ig levels are secondary to frequent infections and/or part of mechanisms that may compensate for the IgA deficiency.     

Kabuki syndrome: description of dental findings in 8 patients

The cardinal features of Kabuki (Niikawa-Kuroki) syndrome (KS) include characteristic facial dysmorphic features, mild to moderate mental deficiency, skeletal abnormalities, dermatoglyphic abnormalities, and postnatal growth retardation. We identified 8 patients with KS in a genetics clinic over the past 5 years. All were Caucasians, except for 2 who were of mixed Aboriginal and Caucasian descent. All had the facial gestalt, the dermatoglyphic abnormalities characteristic of the syndrome, and developmental delay. Dental abnormalities of permanent teeth were seen in all 8 cases; 6 had missing lower incisors. Five patients had uniquely abnormal upper incisor teeth shape; the upper incisors had a 'flat head' screwdriver-shaped appearance. Other dental abnormalities included missing lower lateral incisors, missing second premolars, and ectopic upper 6-year molars. We believe the presence of the unique dental findings will prove useful in the diagnostic assessment of individuals with KS.     

Clinical and pathologic findings of the liver in the acquired immune deficiency syndrome (AIDS)

Clinical data and histologic sections of the liver, including immunohistochemical studies for hepatitis B surface and core antigens, were reviewed in 42 autopsy cases of the acquired immune deficiency syndrome (AIDS). Hepatomegaly, elevation of serum transaminases, and mild elevation of alkaline phosphatase were commonly observed clinical and biochemical abnormalities. Mildly elevated alkaline phosphatase and normal bilirubin levels were present in patients with Mycobacterium avium-intracellulare (MAI) infection, cytomegalovirus (CMV) infection, and Kaposi's sarcoma (KS). Histologic sections demonstrated liver involvement by MAI in eight cases; KS in six cases; cryptococcus in three cases; and CMV in two cases. One case of MAI infection was associated with marked central vein sclerosis, a finding previously unreported. Thirty-two (76%) of 42 cases had serologic or pathologic evidence of hepatitis exposure. Two patients had histologic evidence of chronic active hepatitis. The pathologic processes involving the liver appeared to be secondary to the infections and neoplasms for which this population is susceptible and did not significantly contribute to morbidity or mortality. No findings specific or pathognomic for AIDS were identified in the liver.     

Juvenile rheumatoid arthritis: cellular hypersensitivity and selective IgA deficiency

Although humoral immune mechanisms are currently thought to be of pathogenetic significance in juvenile rheumatoid arthritis (JRA), little is known about the role of cellular hypersensitivity in this disease. A possible association between abnormalities of humoral and cellular immunity exists in patients with ataxia-telangiectasia, who may have absent IgA, abnormal delayed hypersensitivity, or both. As IgA deficiency has been noted in 2–3% of patients with JRA, we have studied selected aspects of humoral and cellular hypersensitivity in patients with JRA and IgA deficiency and in patients with JRA and normal IgA levels. All patients had normal serum levels of complement, IgG, IgM, and IgD.

Cellular hypersensitivity was evaluated by cutaneous delayed-type hypersensitivity, in vitro migration inhibitory factor production, and antigen induced 3H-thymidine incorporation by lymphocytes using Candida and Streptokinase–Streptodornase antigens. Two of four IgA deficient patients had positive in vitro but negative in vivo responses to antigens. Seven of fourteen JRA patients with normal immunoglobulin levels exhibited a similar dissociation of in vivo and in vitro manifestations of delayed hypersensitivity. This pattern of cellular immune response was associated with activity and chronicity of disease; it was independent of IgA deficiency.

     

Association of autoimmunity with IgG2 and IgG4 subclass deficiency in a growth hormone-deficient child

An association between humoral immune deficiency and childhood autoimmune disease has been previously established. We describe a 7-year-old male with severe autoimmune disease, recurrent infections, a marked deficiency of IgG2 and IgG4, and an inability to respond to polysaccharide antigens. This child was also found to have isolated growth hormone (GH) deficiency. Laboratory results included a positive anti-smooth muscle antibody, a positive Raji-cell assay for immune complexes, and normal levels of IgG, IgM, and IgA. IgG subclasses revealed an IgG1 of 1225 (normal for age, 280–1120 mg/dl), IgG2 of <10 (30–630 mg/dl), IgG3 of 36 (40–250 mg/dl), and IgG4 of <4 (11–620 mg/dl). No increase in antibody titer was noted to either Pneumovax or unconjugatedHaemophilus influenzae vaccine. Numbers of circulating B cells (CD19) were markedly diminished (<0.5%). Liver biopsies have shown chronic active hepatitis. Somatomedin C was 0.28 U/ml (normal for age, 0.5–2.06 U/ml). Challenge with eitherl-dopa or clonidine produced a peak GH response of 2.3 ng/ml (normals = >7 ng/ml). Children with autoimmune disorders should be evaluated for IgG subclass deficiencies and ability to make antibody in response to antigen challenge regardless of the serum immunoglobulin levels. Growth failure in immune-deficient children should not be assumed to be due to chronic illness or recurrent infections. Other etiologies for growth failure should be sought.     

Immunoglobulin deficiencies and susceptibility to infection among homozygotes and heterozygotes for C2 deficiency

About 25% of C2-deficient homozygotes have increased susceptibility to severe bacterial infections. C2-deficient homozygotes had significantly lower serum levels of IgG2, IgG4, IgD, and Factor B, significantly higher levels of IgA and IgG3 and levels of IgG1 and IgM similar to controls. Type I (28 bp deletion in C2 exon 6 on the [HLA-B18, S042, DR2] haplotype or its fragments) and type II (non-type I) C2-deficient patients with increased susceptibility to bacterial infection had significantly lower mean levels of IgG4 (p < 0.04) and IgA (p < 0.01) than those without infections (who had a higher than normal mean IgA level) but similar mean levels of other immunoglobulins and Factor B. Of 13 C2-deficient homozygotes with infections, 85% had IgG4 deficiency, compared with 64% of 25 without infections. IgD deficiency was equally extraordinarily common among infection-prone (50%) and noninfection-prone (70%) homozygous type I C2-deficient patients. IgD deficiency was also common (35%) among 31 type I C2-deficient heterozygotes (with normal or type II haplotypes), but was not found in 5 type II C2-deficient heterozygotes or 1 homozygote. Thus, C2 deficiency itself is associated with many abnormalities in serum immunoglobulin levels, some of which, such as in IgG4 and IgA, may contribute to increased susceptibility to infection. In contrast, IgD deficiency appears not to contribute to increased infections and appears to be a dominant trait determined by a gene or genes on the extended major histocompatibility complex (MHC) haplotype [HLA-B18, S042, DR2] (but probably not on type II C2-deficient haplotypes) similar to those previously identified on [HLA-B8, SC01, DR3] and [HLA-B18, F1C30, DR3].     

Tumor necrosis factor (TNF)alpha and its soluble receptor (sTNFR) p75 during acute human parvovirus B19 infection in children

Human parvovirus B19 (HPV) has been shown to be involved in the pathogenesis of various connective tissue and autoimmune diseases. In order to gain more information on HPV possible role in these diseases, we have investigated some immune responses in patients with acute HPV infection, mainly the secretion of the proinflammatory cytokine tumor necrosis factor (TNF)alpha and it's antagonist--the soluble TNF receptor (sTNFR) p75. Thirteen children with acute HPV infection and 13 healthy volunteers were investigated for the presence of autoantibodies, lymphocyte subpopulation counts, levels of total immunoglobulins, IgG subclasses and complement. The levels of TNFalpha and sTNFR p75 were determined in serum and conditioned medium (CM) from unstimulated and LPS stimulated peripheral blood mononuclear cell (PBMC) cultures. There was no difference between patients and controls regarding autoantibodies, lymphocytes, immunoglobulins, IgG subclasses and complement. A significant imbalance between TNFalpha and sTNFR p75 was found in the patients group. TNFalpha concentrations were significantly higher both in sera and in CM from the patients as compared with the controls. The levels of sTNFR concentrations were either similar (in sera) or significantly lower (in CM) in the patients compared with the controls. The TNF index, representing the biologically available TNFalpha, was significantly higher in patient's sera and CMs. In view of these results, it is conceivable that infection with human HPV in otherwise healthy children may lead to a proinflammatory state. The presence of high levels of biologically available TNFalpha, in susceptible individuals, may in turn play a role in the pathogenesis of systemic autoimmune diseases in HPV infected individuals.     

Antibody deficiency in adults with 22q11.2 deletion syndrome

There are limited data on immunological disorders, infection profile, and autoimmunity among adults with the 22q11.2 deletion syndrome (22q11.2DS) in the literature. To expand this knowledge base, we evaluated immunoglobulin levels, lymphocyte subsets, and T-cell function in 26 adults, consecutively referred to our 22q11.2DS multidisciplinary team. Their medical records were also reviewed with respect to frequency and severity of infections and autoimmune disorders. Six patients had low immunoglobulin levels; among these patients, one had a combined IgA and IgG1 deficiency, one had an isolated IgG3 deficiency, and four had a profound antibody deficiency comparable to common variable immunodeficiency (CVID). Three of the patients with profound antibody deficiency showed signs of reduced T-cell function measured as a low response to mitogen and/or antigen stimulation. The four patients with profound antibody deficiency suffered from more severe infections than the rest of the patient group. Three of them also had a history of both immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AHA). Our results suggest that a subgroup of individuals with 22q11.2DS can develop a severe antibody deficiency associated with lower respiratory tract infections and autoimmune conditions. Early diagnosis of hypogammaglobulinemia among these individuals is important in order to provide optimal treatment. We therefore recommend an immunological evaluation and follow-up among adults with 22q11.2DS who have a history of autoimmune conditions or recurrent infections.     

Increased risk of parvovirus B19 infection in young adult cancer patients receiving multiple courses of chemotherapy

An increased human parvovirus B19 infection rate has been observed in immunocompromised hosts. In this study, we sought to determine the prevalence of parvovirus B19 infection in adult cancer patients receiving multiple courses of systemic chemotherapy. From March 1999 through April 2000, 59 men and 68 women, with a median age of 49 (18 to 79) years, were enrolled in this study. They had received an average of 7.1 (4 to 32) courses of systemic chemotherapy. The median duration from the date of starting chemotherapy to the date of blood sampling was 11 (4 to 88) months. Serum B19 immunoglobulin G (IgG) and IgM levels were examined by an enzyme-linked immunosorbent assay, and B19 DNA was examined by a nested PCR. A group of 400 healthy blood donors served as the control group. The overall prevalences of anti-B19 IgG in adult cancer patients and healthy blood donors were 61.4 and 25.0%, respectively (P < 0.01). Anti-B19 IgM and B19 DNA were not detectable in these anti-B19 IgG-seropositive individuals. A further age-stratified comparison revealed that only patients younger than 40 years had a significantly higher anti-B19 IgG seropositivity rate than the controls (19 of 39 versus 53 of 310; P < 0.001). The increased prevalence of B19 infection in these 39 adult patients younger than 40 years might be clinically significant, since unexplained anemia, a common sequela of B19 infection, was detected in 3 of 20 seronegative patients (15.0%) and in 12 of 19 seropositive patients (63.2%) (P < 0.005). The results of this study suggest that adult patients younger than 40 years and receiving multiple courses of systemic chemotherapy may have a significantly increased risk of B19 infection. Prospective studies to define the time course and clinical consequence of B19 infection in this group of patients are needed.