|Year : 2016 | Volume
| Issue : 1 | Page : 30-36
Parvovirus B19 viremia in Egyptian adults with systemic lupus erythematosus
Sanaa S Gazareen1, Samar G Soliman2, Safaa I Tayel3, Emad M El Shebini1, Alaa E Abd El-Hamid1
1 Department of Internal Medicine, Rheumatology and Rehabilitation, Menofia University, Menofia, Egypt
2 Department of Physical Medicine, Rheumatology and Rehabilitation, Menofia University, Menofia, Egypt
3 Department of Medical Biochemistry, Faculty of Medicine, Menofia University, Menofia, Egypt
|Date of Submission||18-Nov-2014|
|Date of Acceptance||27-Jan-2015|
|Date of Web Publication||18-Mar-2016|
Emad M El Shebini
MSc, Department of Internal Medicine, Faculty of Medicine, Menofia University, Yassin Abdel Ghaffar St, Shebin Al-Kom, 32512 Menofia
Source of Support: None, Conflict of Interest: None
This study was undertaken to investigate the seroprevalence of parvovirus B19 DNA in systemic lupus erythematosus (SLE) patients and its correlation with disease activity.
Infection with parvovirus B19 (B19) has been suggested to contribute to the pathogenesis of SLE. B19 infection may simulate both clinical and laboratory features of SLE, presenting either as a potential first-time diagnosis of SLE or as an exacerbation of previously established disease.
Patients and methods
Sera from 30 adult patients with SLE and from 15 normal controls were examined for parvovirus B19 infection by means of nested PCRs to detect B19 DNA.
B19 DNA was detected in two of 15 (13.5%) controls and in 12 (40%) of 30 SLE patients, with no significantly positive rates observed in SLE patients compared with healthy controls (P > 0.05). B19 was positive in seven (58.5%) patients with severe activity compared with 8.3% without activity, 16.7% patients with mild activity, and 16.7% patients with moderate activity. No significant differences were observed between patients with virological positivity and those with virological negativity for B19 infection as regards the activity of SLE or any clinical manifestations of SLE.
Parvovirus B19 infection is not associated with SLE.
Keywords: Nested PCR, parvovirus B19, systemic lupus erythematosus
|How to cite this article:|
Gazareen SS, Soliman SG, Tayel SI, El Shebini EM, Abd El-Hamid AE. Parvovirus B19 viremia in Egyptian adults with systemic lupus erythematosus. Menoufia Med J 2016;29:30-6
|How to cite this URL:|
Gazareen SS, Soliman SG, Tayel SI, El Shebini EM, Abd El-Hamid AE. Parvovirus B19 viremia in Egyptian adults with systemic lupus erythematosus. Menoufia Med J [serial online] 2016 [cited 2020 Apr 7];29:30-6. Available from: http://www.mmj.eg.net/text.asp?2016/29/1/30/178942
| Introduction|| |
Systemic lupus erythematosus (SLE) is the prototypic multisystem autoimmune disorder with a broad spectrum of clinical presentations encompassing almost all organs and tissues. The extreme heterogeneity of the disease has led some investigators to propose that SLE represents a syndrome rather than a single disease . Multiple factors are thought to contribute to the development of immune response to self, including genetics, age, and environment. Several environmental factors have been implicated in the etiology of SLE environmental factors [2,3]. Infections can be responsible for aberrant immune response leading to a loss of tolerance toward native proteins . In particular, viruses, bacteria, and other infectious pathogens are the major postulated environmental triggers of autoimmunity . Many viruses have been implicated in the etiology of SLE, including the Epstein-Barr virus, transfusion-transmitted virus (tissue transplant virus or Torque teno virus), retroviruses, paramyxovirus, cytomegalovirus, parvovirus B19, and corona virus.
Human parvovirus B19 (B19) belongs to the Erythrovirus genus within the Parvoviridae family  and solely infects humans . It was discovered in 1975 when blood donors were screened for hepatitis B. Sample 19 in row B (hence its name parvovirus B19) was found to be a false-positive result . Since its discovery, human parvovirus B19 (B19) has been linked to a broad spectrum of clinical syndromes, including erythema infectiosum, transient aplastic crisis, persistent infection manifesting as pure red cell aplasia in immunocompromised individuals, nonimmune hydrops fetalis, and arthritis .
There are striking similarities between the clinical features and hematological findings of SLE and those of parvovirus B19 infection, including anemia, thrombocytopenia, and arthritis. Parvovirus B19 may be accompanied by a transient subclinical state of autoimmunity and may mimic or exacerbate SLE . This association might reflect the switch from B-cell activation to autoantibody production in predisposed individuals and the secretion of hydrolyzing anti-ssDNA autoantibodies in 30-70% of patients, which hydrolyze viral B19 ssDNA in blood and other fluids .
Parvovirus B19 may have the property of inducing the production of autoimmune antibodies by mimicking autoantigens. This in turn may contribute to or exacerbate the symptoms in SLE. It depletes erythroid progenitor cells by apoptosis. Chronic parvovirus B19 infection is associated with the production of a wide array of autoantibodies .
Similarities in clinical and immunological features of viral infection and SLE at presentation may hinder the differential diagnosis between these two conditions . The occurrence of B19 infection has been documented in patients with SLE, particularly in relation to disease onset .
Parvovirus has been associated with a variety of diseases and much has been written about the pathogenesis. However, the question still remains as to how one single class of viruses can cause such a diverse clinical presentation and influence so many different organ systems .
The objectives of this study were to search for B19-related SLE, identify the clinical characteristics of those patients that could be associated with B19 infection, and determine whether a relation exists between B19 and disease activity.
| Patients and methods|| |
This case-control study was conducted on 30 adults fulfilling the American College of Rheumatology Classification Criteria for SLE  between 2012 and 2014. They were recruited on one of their routine visits to the Internal Medicine Clinic, Rheumatology Clinic, and from the Inpatient Department, Menofia University Hospital, Egypt. They were from Menofia and neighboring governorates. In addition, 15 age-matched and sex-matched healthy adult volunteers were studied as controls.
All patients included in this study were subjected to detailed medical history with particular stress on age of onset of SLE and the duration of the disease. Cases and controls were asked about drugs they were taking that could increase susceptibility to viral infections (e.g. steroids, cyclosporine, azathioprine) and about having associated illnesses (e.g. other inflammatory or malignant diseases) that might affect susceptibility to infections, before enrollment into the study.
The clinical parameters of the disease in each patient were studied, including the affection of various systems by the disease (skin, kidney, central nervous system, joints, serous membranes).
All were subjected to the following investigations: complete blood count, 24-h urine proteins erythrocyte sedimentation rate, C-reactive protein, C3, C4, antinuclear antibody, and anti-dsDNA. Disease activity in patients was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, which was published in 1992. This index measures disease activity within the last 10 days .
In this study we performed nested PCRs to detect B19 DNA in the serum samples from patients and controls.
Detection of parvovirus B19-DNA by nested PCR
DNA was extracted from serum by using a DNA high-pure PCR template preparation kit (Thermoscientific GeneJET Viral DNA (Thermo Fisher Scientific 81, Wyman Street, Waltham, MA, USA) and RNA Purification Kit; Lethwania) as directed by the manufacturer. PCR was performed according to the method of Zerbini et al.  In brief, 0.4 μl of extracted DNA was added to the PCR mix for a total volume of 25 μl of DreamTaq Green PCR MasterMix (2΄) (Thermoscientific (Fisher Biotec, 198 Cambridge St, Wembley, WA 6014, Australia)), 200 μmol/l deoxynucleotide triphosphate (Stratagen (4040 Lake Washington Blvd NE #201, Kirkland, WA 98033, United States)) and 300 ng of each primer. After an initial denaturation step of 5 min at 95°C, the first round of PCR amplification was performed. Thereafter, 3 μl of the first-round product was transferred to a second 50 μl PCR mix. The second-round reaction mix contained the same constituents as the first-round mix, but 300 ng of each second primer was substituted for each first primer. The oligonucleotide primers used in the first round of amplification were 5′-CTTTAGGTATAGCCAAC TGG-3′(Biosearch Technologies, USA) and 5′- ACACTGAGTTTACTAGTGGC-3′, yielding a product of 1112 bp. Second-round PCR was performed with primers 5′-CAAAAGCATGTGGAGTGAGG3′ and 5′-CC TTATAATGGTGCTCTGGG 3′ to give a product of 104 bp.
Thirty-five cycles of both first-round and second-round amplification were performed under the following conditions after one cycle of heating at 95°C for 5 min, at 95°C for 1 min, at 55°C for 1.5 min, and at 72°C for 1 min, followed by a final extension at 72°C for 7 min for one cycle. Ten microliter samples of second-round PCR products were then analyzed by electrophoresis on 2% agarose gel. Bands were visualized by ethidium bromide staining.
Clinical and laboratory data of the cases and controls were tabulated. Statistical analysis was carried out by Statistical Package for Special Sciences (SPSS) version 20 (Chicago, Illinois, USA).
Statistical tests used
- Description of quantitative variables in the form of mean ± SD.
- Description of qualitative variables by frequency and percentage.
- Student's t-test of two independent samples to compare quantitative variables.
- The ν2 -test and the Mann-Whitney U-test to compare qualitative variables.
| Results|| |
B19 DNA was detected by means of nested PCR in two of 15 (13.5%) controls and in 12 of 30 (40%) SLE patients [Table 1]. No significantly positive rates were observed in SLE patients compared with healthy controls (P > 0.05).
|Table 1: Comparison between cases and controls regarding parvovirus B19 DNA|
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However, B19 DNA-positive cases were more likely to be younger (mean age 22.08 years) compared with negative cases (mean age 25.67 years) [Table 2]. There were no significant differences in onset of disease, sex, and family history of lupus.
|Table 2: Association between positive or negative parvovirus DNA cases and clinical manifestations of systemic lupus erythematosus|
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There were no significant differences in anemia, leukopenia, thrombocytopenia, or other clinical characteristics between patients with positive B19 DNA and those negative for B19 DNA [Table 2], despite statistical data demonstrating that mean overall hemoglobin was significantly lower in B19 DNA-seropositive patients (mean Hb 8.6 g/dl) than in B19-negative cases (mean Hb 10.5 g/dl) [Table 2]. The cutoff value of hemoglobin was 9.15 g/dl, with low sensitivity and specificity.
There were no significant differences with respect to proteinuria, hypocomplementemia, erythrocyte sedimentation rate, C-reactive protein, or other serological investigations between patients with virological positivity and those with virological negativity for B19 infection [Table 2].
Finally, B19 was positive in seven (58.5%) patients with severe activity, compared with 8.3% without activity, 16.7% of patients with mild activity, and 16.7% of patients with moderate activity. However, there was no significant difference between cases as regards the activity of SLE [Table 3].
|Table 2: Association between positive or negative parvovirus DNA cases and clinical manifestations of systemic lupus erythematosus|
Click here to view
| Discussion|| |
Several studies sought a possible correlation between the pathogenesis of SLE and infection with certain viruses. A number of exogenous viruses have been linked to the pathogenesis of SLE, of which the Epstein-Barr virus has the most evidence for being an etiological candidate. Other viruses implicated in SLE are human endogenous retroviruses, cytomegalovirus, parvovirus B19, transfusion-transmitted virus, human herpes virus (HHV-6), HHV-7, HHV-8, human papilloma virus, dengue virus, human T-cell lymphotropic virus, and HIV .
Overall, serological and molecular studies have observed antibodies and PCR products to these viruses at higher levels in SLE patients as compared with controls, together with enhanced viral loads. In some cases, these phenomena have been associated with flares of disease activity. In general, these investigations suggest viral triggering or exacerbation of SLE as a direct consequence of a given virus, or indirectly through endogenous viral agents found in humans. At present, there is no consensus of opinion as to which virus has more relevance in the etiology and pathogenesis of SLE, and reaching a consensus is made difficult through publication bias and the paucity of unpublished negative data .
Recent research has focused on the role of parvovirus B19 in the etiopathogenesis of SLE . The similarities in clinical characteristics have led to speculations about the linkage between B19 infection and SLE. A relationship between B19 and lupus can be envisaged in three possibilities: first, some B19-infected patients produce autoantibodies commonly found in patients with SLE, in addition to the production of polyspecific anti-B19 antibodies . Second, clinical and laboratory features identical to those of SLE can occur in B19-infected patients - for instance, a 'slapped cheek' rash, acute polyarthritis, and/or cytopenia with constitutional symptoms including high-grade fever and production of antinuclear antibodies, anti-DNA, and anti-phospholipid antibodies; however, resolution of these manifestations within 1-2 weeks promptly provides the correct diagnosis . Third, SLE could develop in the wake of B19 infection. Furthermore, there have been a few reports of B19 infection coinciding with an exacerbation of known SLE [18,19]; this association might reflect the switch from B-cell activation to autoantibody production in predisposed individuals and the secretion of hydrolyzing anti-ssDNA autoantibodies in 30-70% of patients, which hydrolyze viral B19 ssDNA in blood and other fluids .
Although there exist similarities in clinical features between B19 and SLE, there are striking differences such as the paucity of prolonged fever, absence of characteristic renal involvement, or seizures in B19 infection .
The present study is an attempt to investigate the association between B19 infection and SLE in a reasonable number of patients based on the detection of viral DNA in serum by nested PCR. This technique had the advantage of being very sensitive and suitable for clinical use. Our results show no comparable positivity rates for viral DNA in SLE patients and healthy controls. The prevalence of B19-DNA was 13.5% in healthy controls in our study in comparison with 40% SLE patients.
Our results for SLE patients were in agreement with those of previous studies and cases reports. Bengtsson et al.  did not find an increased prevalence of B19 infection in SLE patients in relation to the general population. In contrast to our results, Hsu and Tsay  detected B19 DNA in 24% of patients with SLE but in none of those with other systemic rheumatic diseases; this discrepancy may be related to the difference in several factors including the sample size (72 cases vs. 30 cases in our study). Trapani et al.  also reported cases of B19-induced SLE. Cope et al.  suggested that this virus may trigger mechanisms leading to an autoimmune response in the form of SLE. Some authors state that parvovirus B19 causes symptoms that only mimic lupus disease, such as vasculitis, arthralgia, and fever episodes .
A number of Arabic studies on SLE patients describing SLE or SLE-like illness associated with human parvovirus B19 infection have been published. El-Eishi et al.  detected parvovirus viremia in 30% of the SLE Egyptian population studied and in none of the normal controls (P < 0.05). A prospective Tunisian epidemiological study was conducted to elucidate the possible role of this infectious agent in the pathogenesis of SLE. The results supported a direct relationship between parvovirus B19 infection and the pathogenesis of SLE .
Many observations in this study are noteworthy. First, somewhat unexpectedly, two normal controls were positive for B19 DNA. This could be explained by the observation in 1975 by Cossart et al. of the presence of viral DNA in healthy blood donors , showing that it could persist for a long period of time despite the absence of clinical manifestations .
Most individuals become infected with B19 during their school years. The patients included in the study were adults. The youngest were two female patients aged 15 years. We found that B19 DNA-positive patients were more likely to be younger (mean age 22.08 years) compared with B19 DNA-negative cases (mean age 25.67 years) [Table 2].
The disease duration of the self-limiting lupus-like disease induced by B19 infection tended to be 2 years or less in most of the reported cases. The common features of self-limited lupus included rash, fever, malaise, fatigue, arthritis, leukopenia, thrombocytopenia, and hypocomplementemia, with a broad spectrum of autoantibodies. Less common ones were oral ulcers and Raynaud's phenomenon. With regard to our patients, the disease duration was shorter in B19 DNA-seropositive cases (mean 22.08 months) than in B19-negative cases (mean 28.67 months).
It is well known that leukopenia, anemia, and thrombocytopenia are the most common findings in active lupus patients. The pathogenic mechanism behind cytopenias in active lupus patients is clear. The probable causes include bone-marrow suppression by immunosuppressive agents or macrophage activation with hemophagocytosis . Also, B19 parvovirus is known to have tropism for erythroid precursors in bone marrow and tends to cause aplastic anemia in immunocompromised hosts or thrombocytopenia in sporadic cases .
In the present study, there was no significant relation between B19 DNA positivity and anemia, leukopenia, or thrombocytopenia in those patients, despite data showing that the mean overall Hb is significantly lower in B19 DNA-seropositive patients (mean Hb 8.6 g/dl) compared with B19-negative cases (mean Hb 10.5 g/dl). The cutoff value was 9.15 g/dl, with very low sensitivity and specificity. These findings were different from the results of Chen et al. , who found significant association of past B19 infection with cytopenia in both adult-onset Still's disease and SLE patients. Pallet et al.  studied B19 infection-associated pediatric SLE patients, concluding that B19 infection should be considered in patients with pediatric SLE associated with a severe are generative anemia.
Another important finding in this study is that lupus patients with B19 DNA were not associated with arthritis, reflecting that the causes of arthritis in SLE may be disease-related rather than B19 infection-related. Our results did not support the findings of previous studies showing that the presence of anti-B19 nonstructural protein 1 (NS1) antibodies might be linked to the development of arthropathy, and the production of anti-NS1 antibodies may predict the progression of B19 infection to persistent arthritis .
There were no significant associations of B19 DNA positivity with nephritis, cerebritis, oral ulcers, rash, serositis, or hypocomplementemia. The last finding was different from another study on pediatric SLE by El-Saadany et al. , who demonstrated a higher prevalence of hypocomplementemia in patients with parvovirus B19 viremia than in those without parvovirus.
Several studies and case reports have implicated B19 in inducing flares of SLE and have shown that treatment of B19 in SLE patients might reduce flare-ups of such a serious disease, and administration of immunoglobulins could be helpful to control infection if discontinuation of the immunosuppressive therapy is not feasible. On studying different degrees of SLE patients, those with PCR-positive and those with PCR-negative test results, we could not detect any statistically significant differences to help delineate a cause-effect relationship with disease activity.
The true prevalence of B19 in SLE is difficult to determine by serological testing because the immunosuppression associated with SLE can inhibit IgM and IgG seroconversion. Clearance of the virus may be impaired because of lack of anti-B19 antibodies either because of the immunocompromised nature of the host or because of the use of immunosuppressive drugs. Viral DNA could integrate into the human chromosome, establishing latency, which could have clinical consequences. In fact, the association of immunocompromised patients with autoimmune phenomena is well known . However, most of our patients were similarly immunosuppressed by steroids and cytotoxic agents in various combinations irrespective of whether or not they were B19 DNA positive.
There are some limitations in our study that need to be addressed; this study still faces the problem of limited number of patients with SLE. We did not examine B19 DNA in bone-marrow hematopoietic cells from lupus patients to exclude the possibility of persistent infection or explore the causal role of B19 infection in anemia. In addition, we did not investigate the serological or bimolecular effects of B19 infection on clinical characteristics in SLE patients. While the clinical and laboratory manifestations of B19 infection and SLE overlap, establishing a direct causal role remains difficult because of the brief window of opportunity during which to establish the diagnosis with IgM antibody serology. In addition, it is unlikely that B19 infection alone induces the development of lupus because circulating B19 DNA is not detectable at the time of lupus diagnosis.
Several studies are in progress that may in the future identify viruses or bacteria as etiological agents in lupus. This will expand the therapeutic perspectives for SLE in the form of anti-infectious agents in the treatment of SLE and vaccinations, which could be used for the prevention of disease onset in SLE  [Figure 1].
|Figure 1: Agaros gel electrophoretic profi le of the nested PCR products. Arrows point to positive parvovirus B19 viral DNA cases in lanes 2, 3, and 4, whereas lanes 1 and 5– 8 show negative cases using 100 bp ladder.|
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| Conclusion|| |
B19 is an emerging pathogen in autoimmune diseases; however, we could not show an association between parvovirus B19 and SLE manifestations or disease activity. Although our results are compatible with some previous studies, they differ from others. These conflicting results could be explained by nonstandardized selection of case and control groups, the comparison criteria, follow-up periods, tests performed, and inter-regional genetic and socioeconomic variables. Further, prospective, multicenter studies are needed to assess the role of many infectious agents including B19 on SLE etiopathology.
| Acknowledgements|| |
Conflicts of interest
| References|| |
Bertsias G, Cervera R, Boumpas DT. Systemic lupus erythematosus: pathogenesis and clinical features. Diunduh 12 April 2012; pp: 476-505. Available at: http://www.eular.org/edu_textbook.cfm.
[Last accessed on may 2014].
Gazareen S, El-Najjar M, Yassien YS, Dawood AA, El Shebinie E, Soliman SG, El-Saied JK. Prolactin hormone: a possible marker of the activity of systemic lupus erythematosus. MMJ 2009; 22
Francis L, Perl A. Infection in systemic lupus erythematosus: friend or foe? Int J Clin Rheumtol 2010; 5
Vista SE, Darise Farris A, James JA. Robert G. Lahita. Roles for infections in systemic lupus erythematosus pathogenesisSystemic lupus erythematosus.
5th ed. Academic Press 2011; 1
Ercolini AM, Miller SD. The role of infections in autoimmune disease. Clin Exp Immunol 2008; 155
The International Committee on Taxonomy of Viruses. Virus taxonomy update. Arch Virol 1993; 133
Van Beers-Tas MH, Heidema J. Review: pathogenesis of parvovirus infections in children. Virol Mycol 2013; 2
Cossart YE, Field AM, Cant B, Widdows D. Parvovirus-like particles in human sera. Lancet 1975; 1
Barah F, Whiteside S, Batista S, Morris J. Neurological aspects of human parvovirus B19 infection: a systematic review
. Rev Med Virol.: John Wiley & Sons Ltd.; 2014; 24
Rigante D, Mazzoni MB, Esposito S. The cryptic interplay between systemic lupus erythematosus and infections. Autoimmun Rev 2014; 13
Aslanidis S, Pyrpasopoulou A, Kontotasios K, Doumas S, Zamboulis C. Parvovirus B19 infection and systemic lupus erythematosus: activation of an aberrant pathway? Eur J Intern Med 2008; 19
Trapani S, Ermini M, Falcini F. Human parvovirus B19 infection: its relationship with systemic lupus erythematosus. Semin Arthritis Rheum 1999; 28
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992; 35
Zerbini M, Musiani M, Gentilomi G, Venturoli S, Gallinella G, Morandi R. Comparative evaluation of virological and serological methods in prenatal diagnosis of parvovirus B19 fetal hydrops. J Clin Microbiol 1996; 34
Nelson P, Rylance P, Roden D, Trela M, Tugnet N. Viruses as potential pathogenic agents in systemic lupus erythematosus, Lupus 2014; 23
Chen DY, YM Chen, JL Lan, BS Tzang, CC Lin, TC Hsu. Significant association of past parvovirus B19 infection with cytopenia in both adult-onset Still′s disease and systemic lupus erythematosus patients. Clinica Chimica Acta 2012; 413
Chassagne P, Mejjad O, Gourmelen O, Moore N, Le Loet X, Deshayes P. Exacerbation of systemic lupus erythematosus during human parvovirus B19 infection. Br J Rheumatol 1993; 32
Diaz F, Collazos J, Mendoza F, De La Viuda JM, Cazallas J, Urkijo JC, Flores M. Systemic lupus erythematosus associated with acute parvovirus B19 infection. Clin Microbiol Infect 2002; 8
Bengtsson A, Widell A, Elmstahl S, Sturfelt G. No serological indications that systemic lupus erythematosus is linked with exposure to human parvovirus B19. Ann Rheum Dis 2000; 59
Hsu TC, Tsay GJ. Human parvovirus B19 infection in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2001; 40
Cope AP, Jones A, Brozovic M, Shafi MS, Maini RN. Possible induction of systemic lupus erythematosus by human parvovirus. Ann Rheum Dis 1992; 51
Pavlovic M, Kats A, Cavallo M, Shoenfeld Y. Clinical and molecular evidence for association of SLE with parvovirus B19. Lupus 2010; 19
El-Eishi N, EL-Eishi H, Shaker O, Soliman A, El-Mehallawy F. Parvovirus B19 viremia in Egyptian patients with systemic lupus erythematosus. Egypt Dermatol Online J 2006; 2
Kaddachi I. Parvovirus B19 infection, systemic lupus erythematosus and Behçet′s disease: coincidence or triggering agent? Int J Appl Sci Technol 2013; 3
Delmas S, Lefrere J-J, Morinet F, Pillet S. Advances in human B19 erythrovirus biology. J Virol 2010; 84
Brown KE, Hibbs JR, Gallinella G, Anderson SM, Lehman ED, McCarthy P, Young NS. Resistance to parvovirus B19 infection due to lack of virus receptor (erythrocyte P antigen). N Engl J Med 1994; 330
Pallet B, Sauvion S, Salomon R, Quartier P. B Bader-Meunier Pediatric systemic lupus erythematosus and human parvovirus B19 infection. Pediatr Rheumatol 2011; 9
El-Saadany H,Talat M, Salah H. Parvovirus B19 viremia in children with systemic lupus erythematosus. Egypt J Pediatr Allergy Immunol 2011; 9
Kerr JR. Pathogenesis of human parvovirus B19 in rheumatic disease. Ann Rheum Dis 2000; 59
Bach JF. Infections and autoimmune diseases. J Autoimmun 2005; 25
[Table 1], [Table 2], [Table 3]