Frequent infection with a viral pathogen,parvovirus B19, in rheumatic diseases of childhood

OBJECTIVE: To find further evidence of the association of parvovirus B19 infection with juvenile rheumatic diseases, and to get new insights into the immunopathogenesis of these diseases. METHODS: Paired serum and synovial fluid samples from 74 children with rheumatic disease were analyzed with respect to their content of viral DNA and antibodies directed against the B19 viral proteins VP1, VP2, and NS1. Control sera from 124 children with noninflammatory bone diseases or growth retardation were also analyzed. The sequence of the viral DNA, amplified by polymerase chain reaction (PCR), was determined. IgG-complexed virus was isolated from sera and synovial fluid by adsorption to protein A beads. The amount of free virus versus immunocomplexed virus particles was determined by quantification of the viral genomes by quantitative PCR. RESULTS: Twenty-six of the 74 patients (35%) had detectable amounts of parvovirus B19 DNA in the serum (n = 22 [30%]) and/or the synovial fluid (n = 16 [22%]), whereas only 9 of the 124 control sera (7%) were positive for the viral DNA (P < 0.0001). Forty-six patients (62%) had serum IgG against the structural proteins, indicating past infection with B19. NS1-specific antibodies were detected in sera from 29 patients (39%) and 27 controls (22%) (P < 0.001). In addition, 3 patients (4%) showed VP2-specific IgM. In 15 patients, viral DNA could be repeatedly detected in followup samples of serum and synovial fluid. Sequencing revealed low-degree nucleotide variations that are in the range of genotype 1 of parvovirus B19. Immunocomplexed virus was present in varying amounts, both in the sera and in the synovial fluid samples. CONCLUSION: Parvovirus B19 is frequently found in serum or synovial fluid of children with rheumatism. The rate of persistent B19 infection in these patients is significantly higher than in age-matched controls.     

Frequent infection with a viral pathogen,parvovirus B19, in rheumatic diseases of childhood

Objective

To find further evidence of the association of parvovirus B19 infection with juvenile rheumatic diseases, and to get new insights into the immunopathogenesis of these diseases.

Methods

Paired serum and synovial fluid samples from 74 children with rheumatic disease were analyzed with respect to their content of viral DNA and antibodies directed against the B19 viral proteins VP1, VP2, and NS1. Control sera from 124 children with noninflammatory bone diseases or growth retardation were also analyzed. The sequence of the viral DNA, amplified by polymerase chain reaction (PCR), was determined. IgG‐complexed virus was isolated from sera and synovial fluid by adsorption to protein A beads. The amount of free virus versus immunocomplexed virus particles was determined by quantification of the viral genomes by quantitative PCR.

Results

Twenty‐six of the 74 patients (35%) had detectable amounts of parvovirus B19 DNA in the serum (n = 22 [30%]) and/or the synovial fluid (n = 16 [22%]), whereas only 9 of the 124 control sera (7%) were positive for the viral DNA (P < 0.0001). Forty‐six patients (62%) had serum IgG against the structural proteins, indicating past infection with B19. NS1‐specific antibodies were detected in sera from 29 patients (39%) and 27 controls (22%) (P < 0.001). In addition, 3 patients (4%) showed VP2‐specific IgM. In 15 patients, viral DNA could be repeatedly detected in followup samples of serum and synovial fluid. Sequencing revealed low‐degree nucleotide variations that are in the range of genotype 1 of parvovirus B19. Immunocomplexed virus was present in varying amounts, both in the sera and in the synovial fluid samples.

Conclusion

Parvovirus B19 is frequently found in serum or synovial fluid of children with rheumatism. The rate of persistent B19 infection in these patients is significantly higher than in age‐matched controls.

     

Different patterns of disease manifestations of parvovirus B19-associated reactive juvenile arthritis and the induction of antiphospholipid-antibodies

Children with rheumatic oligo- and polyarthritis frequently establish persistent parvovirus B19 infections, which may be associated with the production of antiphospholipid antibodies. Reported in this paper are the data of five girls with polyarticular rheumatic diseases of different types and persistent parvovirus B19 infection associated in four cases with the presence of antibodies against phospholipids. Clinical parameters, virus load, and antiphospholipid-IgG levels were determined during an observation period up to 92 months. In two patients, erythema infectiosum preceded the development of arthritis and B19 viremia persisted. Two other girls showed antibodies against parvoviral structural proteins at time of the manifestation of the rheumatic disease. Subsequent samples also revealed persistent B19 infection. In the fifth patient, parvovirus B19-specific IgG antibodies were detected for the first time after 120 months of progressing disease at an age of 11 1/2 years. Five years later, quantitative polymerase chain reaction (PCR) revealed viral DNA. In a synovial tissue specimen subsequently obtained, parvovirus B19 structural proteins could be detected by immunohistochemistry. Three of five patients recovered completely without severe sequels. One patient is in remission under immunosuppressive therapy. The fifth patient suffers from progressive erosions despite intensive therapeutical efforts. In consequence, parvovirus B 19 should generally be taken into consideration as a trigger of various forms of juvenile arthritis and persistence of infection should be evaluated.     

Similarities of specificity and cofactor dependence in serum antiphospholipid antibodies from patients with human parvovirus B19 infection and from those with systemic lupus erythematosus

Objective. To assess the phospholipid specificity and immunoglobulin isotype of antiphospholipid (aPL) antibodies in patients with acute parvovirus B19 infection. Methods. Specificity of aPL and isotype distribution in the negatively charged phospholipids, cardiolipin and phosphatidyl serine, and in the neutral phospholipid, phosphatidyl ethanolamine, were measured in the sera of patients with acute parvovirus B19 infections (n = 12), in those with other acute viral infections (n = 10), and in those with syphilis (n = 15) by enzyme-linked immunosorbent assays. The dependence of anticardiolipin (aCL) binding on the presence of β₂-glycoprotein I (β₂-GPI) as a binding cofactor was assessed in these same groups, and was compared with sera from systemic lupus erythematosus (SLE) patients (n = 11) with raised aCL antibody reactivity. Results. Antibodies against any of the 3 phospholipids were found in all 3 groups of patients with infections (B19 in 11 of 12 patients, other viral infections in 8 of 10 patients, and syphilis in 14 of 15 patients). B19 patients' sera contained predominantly IgG antibodies against the negatively charged phospholipids, cardiolipin and phosphatidyl serine, and differed in their specificity and isotype distribution from those found in the other 2 patient groups. B19-associated aCL increased their binding to antigen in the presence of β₂-GPI as a binding cofactor, similar to aCL found in SLE patients, but unlike antibodies from patients with other viral infections or from those with syphilis. Conclusion. The results show the remarkable similarity in specificity of aPL antibodies between B19-infected patients and SLE patients, and raise the question of whether parvovirus infection may be a trigger for the development of aPL antibodies in autoimmune diseases.     

Characteristics of high-titer IgG antiphospholipid antibody in systemic lupus erythematosus patients with and without fetal death

Although high-titer IgG antiphospholipid antibody (aPL) is a predictor of mid-pregnancy fetal death in women with systemic lupus erythematosus (SLE), some SLE patients with high-titer aPL carry pregnancies normally, and to term. To determine potential antibody differences between IgG aPL-positive women with and without fetal death, we studied aPL isotype, subclass, anticoagulant activity, phospholipid specificity, and antibody avidity in selected sera from pregnant SLE patients with high-titer IgG aPL. For controls, we selected sera from pregnant SLE patients who had negative results on tests for IgG aPL (with and without fetal loss). None of the specified antibody characteristics distinguished between the aPL-positive patient groups, nor were other specificities defined in IgG aPL-negative sera from women with fetal death. Although high-titer aPL is a good predictor of fetal death, currently known characteristics, other than a high titer of aPL, do not identify which women will experience this complication.     

Lack of association of beta2-glycoprotein I polymorphisms Val247Leu and Trp316Ser with antiphospholipid antibodies in patients with thrombosis and pregnancy complications

Beta2-glycoprotein I (beta2GPI) is an important target antigen for antiphospholipid antibodies (aPL) and thus beta2GPI polymorphisms may influence aPL production and the development of antiphospholipid syndrome. We have studied the relationship between the Val247Leu and Trp316Ser beta2GPI polymorphisms and the aPL status of 230 patients referred for aPL screening. Sixty-one (26.5%) had persistent aPL [anticardiolipin antibodies (IgG and/or IgM), lupus anticoagulants and/or IgG anti-beta2GPI antibodies]. A comparison of the genotypic and allelic frequencies of these two polymorphisms between the Caucasian patient population and an ethnic-matched normal control group (n = 308) showed no significant differences between aPL-positive patients, aPL-negative patients and the normal control group. This suggests that the Val or Leu allele at position 247 and the Trp or Ser allele at position 316 of beta2GPI do not play a role in the production of aPL. There was a significantly decreased prevalence of the Ser316 allele in aPL-negative women (n = 98) when compared with female normal control subjects (n = 249) [0.020 [95% confidence interval (CI) 0.00-0.04]vs 0.060 (95% CI 0.04-0.08), P = 0.0286]. Subgroup analysis showed no significant difference between female patients with thrombosis and female normal control subjects. Thus, the Ser316 allele may protect women from developing pregnancy complications by influencing an anticoagulant function of beta2GPI via a mechanism distinct from aPL production.     

Anti-beta 2 glycoprotein 1 and anti-annexin V antibodies in women with recurrent miscarriage

While it has been established that anti-phospholipid antibodies (aPL) are associated with recurrent miscarriage (RM), the importance of anti-beta2 glycoprotein 1 (GP1) IgG and anti-annexin V IgG antibodies as risk factors for RM is undefined. We have investigated the prevalence of anti-beta2 GP1 IgG and anti-annexin V IgG antibodies in 54 aPL-positive and 48 aPL-negative women with RM. The prevalence of IgG anti-beta2 GP1 antibodies was not significantly different in persistently aPL-positive women with RM (7%), aPL-negative women with RM (6%) and the normal parous control group (3%). Anti-annexin V IgG antibody prevalence was significantly increased in aPL-positive women with RM compared with aPL-negative women with RM (P = 0.01). The elevations were found in 35%, 19% and 16% of aPL-positive women with RM, aPL-negative women with RM and the control group respectively. No women showed positivity for both anti-beta2 GP1 IgG and anti-annexin V antibodies. Anti-beta2 GP1 IgG antibodies do not appear to be contributory to the investigation of women with RM. Anti-annexin V antibody positivity, although associated with aPL positivity in women with RM, is not an independent risk marker.     

Viral infections and antiphospholipid antibodies

OBJECTIVE: To study the relationship between viral infections and the induction of antiphospholipid (aPL) antibodies. METHODS: We reviewed the medical literature from 1968 until 2000 using MEDLINE and the key words virus, infection, antiphospholipid, and anticardiolipin. RESULTS: Anticardiolipin antibodies and/or lupus anticoagulant were associated with a number of viral infections, including hepatitis C virus, human immunodeficiency virus, cytomegalovirus, varicella zoster, Epstein-Barr virus, adenovirus, and parvovirus B. In many instances, the presence of these antibodies was associated with thrombosis. CONCLUSION: The clinical significance of finding aPL antibodies in patients with viral infections remains unknown. In some patients, these antibodies may be transient and disappear within 2 or 3 months. In other susceptible individuals, they may persist and raise the question of whether infections may trigger the development of aPL antibodies in autoimmune diseases.     

Antiphospholipid antibodies in response to infection

An association between infections and antiphospholipid antibodies (aPL) has been reported in several epidemiologic and experimental studies. Infection-induced aPL have been traditionally regarded as transient and were generally not associated with clinical features of antiphospholipid syndrome. The distinction between autoimmune and postinfectious aPL on the basis of requirement of binding cofactor is not absolute, and in recent years, several reports demonstrated that some patients can produce pathogenic antibodies in response to infection. Infections most frequently associated with antiphospholipid syndrome include parvovirus B19, cytomegalovirus, varicella-zoster virus, HIV, streptococcal and staphylococcal infections, gram-negative bacteria, and Mycoplasma pneumoniae.     

Self-assembled B19 parvovirus capsids, produced in a baculovirus system, are antigenically and immunogenically similar to native virions.

B19 parvovirus is pathogenic in humans, causing fifth disease, transient aplastic crisis, some cases of hydrops fetalis, and acquired pure red cell aplasia. Efforts to develop serologic assays and vaccine development have been hampered by the virus's extreme tropism for human bone marrow and the absence of a convenient culture system. We constructed recombinants containing either the major (VP2) or minor (VP1) structural proteins of B19 in a baculovirus-based plasmid, from which the polyhedrin gene had been deleted; these recombinant plasmids were used to generate recombinant infectious baculovirus. Subsequent infection of insect cells in vitro resulted in high-level expression of either B19VP1 or VP2. Parvovirus capsids were obtained by self-assembly in cell cultures coinfected with either VP1- and VP2-containing baculoviruses or, surprisingly, VP2-containing baculoviruses alone. Empty B19 capsids composed of VP1 and VP2 could replace serum virus as a source of antigen in a conventional immunoassay for detection of either IgG or IgM antiparvovirus antibodies in human serum. Immunization of rabbits with capsids composed of VP1 and VP2 resulted in production of antisera that recognized serum parvovirus on immunoblot and neutralized parvovirus infectivity for human erythroid progenitor cells. Baculovirus-derived parvovirus antigen can substitute for scarce viral antigen in immunoassays and should be suitable as a human vaccine.     

Parvovirus B19 may have a role in the pathogenesis of juvenile idiopathic arthritis

OBJECTIVE: To determine the prevalence of human parvovirus B19 infection in patients with juvenile idiopathic arthritis (JIA) by detection of specific IgM, IgG, and viral DNA. METHODS: Serum samples of 50 patients with diagnosis of JIA and 39 healthy controls were analyzed by ELISA to detect IgG and IgM anti-B19-specific antibodies. The parvovirus B19 genome was detected by nested polymerase chain reaction (PCR). The average age of the patients was 9.6 years (2-14 yrs); 30 were female (60%) and 20 male (40%). The definitive diagnoses of these patients corresponded to 19 systemic forms (38%), 11 to the oligoarticular variety (22%) and 20 to the polyarticular (40%). The average age of the control group was 7.8 years (2-16 yrs); the distribution by sex was 25 females (64%) and 14 males (36%). RESULTS: IgM against parvovirus B19 was detected in 20% of the cases (10 patients) and B19 DNA genome by PCR in 48% (24 patients); in 10% of the cases (5 patients), both markers were detected. IgG was found in 32% (16 patients). In the control group neither IgM nor the viral genome was detected. However, 43.5% of the controls (17/39) had IgG against parvovirus B19, indicating past infection by the virus. CONCLUSION: Our study confirms recent observations regarding a high prevalence of viral DNA in JIA patients and a possible role of this viral infection in JIA pathogenesis.     

Parvovirus B19 infection in children with acute lymphoblastic leukemia is associated with cytopenia resulting in prolonged interruptions of chemotherapy.

BACKGROUND: Parvovirus B19 infection causes severe cytopenia and can mimic a leukemic relapse or therapy-induced cytopenia in patients with hematologic malignancies. We evaluated the complications of parvovirus B19 infection, including delays in the scheduled course of chemotherapy, in children with acute lymphoblastic leukemia (ALL). METHODS: Consecutive bone marrow samples were collected from 117 children with ALL and were analyzed for parvovirus B19 DNA by polymerase chain reaction. Clinical and laboratory data were collected from the Nordic Childhood Leukemia Registry and from medical records. RESULTS: Among the 117 children with ALL, 18 (15%) were found to be parvovirus B19 DNA positive. The infection was suspected on clinical grounds in only 1 of these 18 patients. Patients with viremia at diagnosis or during therapy for infection had lower viral loads (median viral load, 7 x 10(4) copies/mL) than did those who became viremic during maintenance therapy (median viral load, 2 x 10(8) copies/mL). The former group also had fewer clinical complications. Indeed, when parvovirus B19 DNA was present during the maintenance treatment, the number of complications (including cytopenia) increased, causing significantly longer periods without chemotherapy (median duration without chemotherapy, 59 days vs. 30 days; P < or = .05) and a higher number of blood transfusions (P = .018) in parvovirus B19 DNA-positive patients than in parvovirus B19 DNA-negative patients. CONCLUSIONS: Children with ALL who were infected with parvovirus B19 became cytopenic, leading to reduced treatment intensity and to complications during treatment. Screening for parvovirus B19 DNA by quantitative polymerase chain reaction in pediatric patients with ALL and unexplained cytopenia is suggested.     

Persistent parvovirus B19 infection detected by specific CD4+ T‐cell responses in a patient with hepatitis and polyarthritis

We, here, report the case of a parvovirus B19 infection in an immunocompetent male patient presenting with acute hepatitis and polyarthritis. To follow the course of infection, we used a previously established enzyme‐linked immunosorbent spot assay (ELISPOT) technique to detect CD4+ T cells specific for viral proteins. Even though symptoms of arthritis and hepatitis resolved in the immunocompetent individual within a few weeks, viral DNA in serum and CD4+ T cells specific for the viral protein VP1 unique region were still detectable more than 6 month after the onset of symptoms, thus pointing to a persistent state of infection. On the basis of this observation, we hypothesize that the intensity of liver involvement correlates with the likelihood of developing persistent parvovirus B19 infection. The described ELISPOT technique to detect virus‐specific CD4+ T cells provides an excellent tool to analyse the state of parvovirus B19 infection for future studies to test this hypothesis.     

Primary Thrombosis Prophylaxis in Antiphospholipid Antibody–Positive Patients: Where Do We Stand?

Persistently positive antiphospholipid antibodies (aPLs) with thrombosis and/or pregnancy morbidity are the hallmark of the antiphospholipid syndrome. However, aPL-positive patients with no prior history of thrombosis exist. On the basis of a limited number of studies that predominantly included systemic lupus erythematosus patients, aPL-positive patients without previous thrombosis have a 0% to 3.8% annual incident thrombosis risk. Given that every positive aPL test is not clinically significant and every aPL-positive patient does not have the same thrombosis risk, risk stratification (based on aPL profile, age, systemic autoimmune diseases, and traditional cardiovascular disease or venous thrombosis risk factors) is crucial to determine the first thrombosis risk in aPL-positive patients. The optimal primary thrombosis prevention strategy in patients with clinically significant aPL profiles should include 1) regular monitoring and elimination of non-aPL thrombosis risk factors, 2) aggressive management of clinical and subclinical systemic autoimmune disease activity, and 3) patient counseling and education. The protective effect of low-dose aspirin against incident thrombosis in patients with clinically significant aPL profiles is not supported by randomized controlled data; general population cardiovascular disease risk prediction tools and prevention guidelines formulated based on risk–benefit calculations should play a role in the decision whether to recommend low-dose aspirin. The effectiveness of hydroxychloroquine, statins, or their combination remains to be determined by well-designed randomized controlled trials.     

Improved diagnosis of gestational parvovirus B19 infection at the time of nonimmune fetal hydrops

BACKGROUND: In the diagnosis of parvovirus B19 infection, the detection of virus-specific IgG in the absence of virus-specific IgM is considered to indicate past immunity. METHODS: We determined the diagnostic value of a high-quality B19 IgM EIA, compared with that of a VP1 IgG avidity EIA, a VP2 IgG epitope-type specificity (ETS) EIA, and real-time polymerase chain reaction (PCR) in the diagnosis of maternal B19 infection during nonimmune fetal hydrops. RESULTS: Serum samples from 101 pregnant women with confirmed B19-induced fetal hydrops were collected at the time of invasive prenatal diagnosis. The samples were investigated for B19 IgM, VP1 IgG avidity, and VP2 IgG ETS. With the B19 IgM EIA, 78 women (77.2 %) showed positive results, 15 (14.9%) showed negative results, and 8 (7.9 %) showed equivocal results. According to the combined B19 IgG avidity and IgG ETS EIA results, only 5 (5%) of 101 women were classified as having past immunity. Available serum samples (n = 24) that had nondiagnostic results in the antibody assays were further investigated by PCR. All were B19 DNA positive (mean load, 2.5 x 10(4) genome equivalents/mL; range, 2.5 x 10(3) - 7.8 x 10(6)). CONCLUSIONS: At the time of B19-induced hydrops, detection of B19 DNA in maternal blood had the best diagnostic sensitivity for identifying maternal B19 infection. However, given the long persistence of B19 DNAemia, supplementary measurement of VP1 IgG avidity and VP2 IgG ETS improves the precision of diagnosis and management of pregnant women affected by the B19 virus.     

Paediatric systemic lupus erythematosus: prognostic impact of antiphospholipid antibodies

OBJECTIVES: The aim of our study was to investigate the prognostic impact of aPL in paediatric onset systemic lupus erythematosus (p-SLE). METHODS: This retrospective study included 56 patients with p-SLE. Chi2-test, Fisher's exact test, incidence rate ratio and Kaplan-Meier survival curves were used to compare aPL-positive and aPL-negative patients considering the value of SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for SLE) at the end of follow-up, the occurrence of thromboses, organ system involvements and need for immunosuppressive treatment in addition to corticosteroids. RESULTS: Anti-cardiolipin antibodies and lupus anticoagulants were detected in 27 (49%) and 19 (35%) patients, respectively. These aPL were frequently transient or intermittent (10 and 15 cases, respectively), and only rarely persistent over time (five cases). The risk of thrombosis was significantly higher (odds ratio = 6.42) and occurred earlier in the presence of aPL, especially if aPL were persistent (P < 0.05). The association between aPL and neurological, renal, haematological manifestations or need for immunosuppressive treatment was not statistically significant. After a mean follow-up of 7.2 yrs, 30 patients (54.5%) had an SDI score > or = 1. The risk of damage (SDI > or = 1) in aPL-positive patients was three times higher than in aPL-negative patients (P < 0.05). Four of the six fatal cases occurred in the aPL-positive group. CONCLUSIONS: The presence of aPL in p-SLE could represent not only a risk factor for thrombosis but also a poor prognostic factor overall.     

Incidence of postpartum thrombosis and preterm delivery in women with antiphospholipid antibodies and recurrent pregnancy loss

OBJECTIVE: To determine the frequency of preterm deliveries and postpartum thrombotic events (TE) in pregnancies resulting in live birth in women with antiphospholipid antibodies (aPL) and a history of recurrent pregnancy loss (RPL) but without prior TE. METHODS: We reviewed the pregnancy outcomes of women referred to our clinic with a history of RPL. Prepregnancy investigation of RPL included history of TE and aPL positivity (anticardiolipin IgG and lupus anticoagulant). We recorded use of anticoagulation therapy during and after pregnancy, obstetric outcome, gestational age at delivery, and postpartum course. Included in our study were women with unexplained RPL with no history of TE attending our clinic who subsequently had pregnancies that resulted in a live birth. RESULTS: Over a 5-year period, 260 women with RPL and no history of TE had a live birth at our clinic. Eighty-seven (33.5%) were positive for aPL and 173 (66.5%) were negative for aPL. Twenty-four percent of deliveries in the aPL-positive group occurred before 37 weeks' gestation compared to 9.8% of deliveries in the aPL-negative group (p = 0.004; 95% CI 0.052-0.234). There were no antepartum TE in either group. One woman in the aPL-positive group (1.1%) had a deep vein thrombosis 3.5 weeks postpartum while receiving prophylactic anticoagulant therapy, compared to none in the aPL-negative group. CONCLUSION: A significantly higher proportion of aPL-positive patients had preterm deliveries compared to aPL-negative patients, but pregnancy-related TE was infrequent: 99.0% of aPL-positive women with a history of RPL and no prior TE who had a live birth at our clinic had an uneventful pregnancy, delivery, and postpartum course.     

Prevalence of human parvovirus B19 and TT virus in a group of young Haemophiliacs in South Africa

A well recognized hazard of transfusion with blood or blood products is the acquisition of a viral infection. Parvovirus B19 and transfusion transmitted virus (TTV) are two of several non-enveloped viruses that may on rare occasions be present in coagulation factor concentrates. The prevalence of these viruses in the South African Haemophilia population has not previously been studied. Thirty-nine Haemophiliac children were investigated for evidence of parvovirus and TTV infection. 26 boys with Haemophilia A had been treated with cryoprecipitate or intermediate purity factor VIII, and 13 boys with Haemophilia B had received prothrombin complex concentrates. All the plasma products were prepared from South African donors and were virally inactivated by heat or solvent/detergent since 1992. A control group of 32 children who had not been transfused were also studied. IgG antibodies to B19 were present in 29 of the 39 patients (74%), 18/26 (69%) with Haemophilia A and 12 of the 13 (85%) with Haemophilia B. None of the patients was IgM antibody positive but two children were PCR positive for B19 DNA. Of the control children, 47% had IgG antibodies to B19, but none were IgM antibody or B19 DNA positive. TTV viral DNA was found in 10.2% of patients and in 9% of the control group. The results indicate that our locally produced plasma products are not a significant source of TTV transmitted infection but may contribute to infection by B19 parvovirus.     

Prevalence of parvovirus B19 DNA in bone marrow of patients with haematological disorders.

Patients with haematological disorders (n = 100) were examined for prevalence of parvovirus B19 DNA in the bone marrow and serum, irrespective of B19-related symptoms. B19 DNA was studied using 2 nested PCRs and the serum samples were further analysed with B19-specific IgG, IgM and avidity as well as seroreactivity against linear and conformational epitopes of the B19 VP2 antigen. The latter assays specify whether the IgG antibody response represents acute or past B19 infection. B19 DNA was detected in 4 of the 100 bone marrow samples, whereas all the serum samples were B19 DNA negative. None of the 4 B19 DNA positive patients had symptoms typical of B19 infection and serology showed past infection. Furthermore, 2 were still B19 DNA positive in bone marrow more than 1 y after the first sample indicating virus persistence. The seroprevalence for B19 IgG was 59% and 2 patients were B19 IgM positive. Thus, presence of B19 DNA in bone marrow from patients with haematological disorders is not a general finding in seropositive patients. B19 DNA can persist in bone marrow, but in our material this finding showed no clear correlation with symptomatic B19 infection.     

No serological indications that systemic lupus erythematosus is linked with exposure to human parvovirus B19

OBJECTIVES: Infectious agents like parvovirus have been implicated as exogenous factors that could trigger onset of systemic lupus erythematosus (SLE). A number of case reports describing a SLE-like presentation of acute human parvovirus B19 infection have been published, but no systematic investigation of the actual seroprevalence in epidemiologically defined SLE populations has previously been reported. METHODS: Sera from 99 SLE patients from a defined area in Southern Sweden, representing 88% of all new SLE cases 1981-1995 within the Lund-Orup Health Care district with 175 000 adult inhabitants (> 15 years of age), and sera from 99 age and sex matched healthy controls were investigated for the presence of IgG parvovirus antibodies. Two different commercially available EIA kits were used; one using E coli synthesised parvovirus VP1/VP2 antigen, and one using baculovirus derived parvovirus VP2 antigen. RESULTS: The EIA using baculovirus derived antigen was more sensitive and surprisingly the controls were more often positive than the SLE patients were (79% versus 65%, chi(2) p=0.027). No difference between the groups was seen with the EIA using E coli derived antigen (46% versus 49%). Titration experiments indicated that the discordance between the two tests was a matter of sensitivity rather than specificity. CONCLUSION: No evidence was found of human parvovirus B19 infection being more prevalent among SLE patients. On the contrary, in one of the parvovirus EIAs the controls were more often positive than the SLE patients were.