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Objective: In the recent months, there have been several case reports and case series on COVID-19 in patients with systemic lupus erythematosus(SLE). We conducted a pooled analysis and systematic review to summarise the findings of these articles. Besides, we aimed to determine the predictors of severe COVID-19 infection in SLE by comparing the mild to moderate cases with the severe to critical ones., Method: All case reports and case series pertaining to COVID-19 in SLE were retrieved from Pubmed, Wiley Online Library, Springer Link, Science Direct and Web of Science databases using 'lupus', 'systemic lupus erythematosus', 'coronavirus', 'SARS-CoV-2', 'SLE' and "Covid-19" as keywords. The following data were extracted from the selected articles: country, age of the patient and the characteristics of SLE such as disease duration, organ or system involved, baseline medications and the severity of the COVID-19 infection. Data extracted from the articles were utilised to perform the pooled analysis., Results: A total of 24 articles with 48 patients met the eligibility criteria. The median age at diagnosis of COVID-19 infection was 41 years (IQR: 11-66 years). The median SLE disease duration prior to the diagnosis of COVID-19 was 9 years (IQR: 0-30 years). A total of 22 (45.83%) patients had severe to critical COVID-19. This pooled data did not demonstrate any difference in the baseline medications between the 2 groups. Patients with lupus nephritis were significantly more prone to develop severe to critical disease ( p = 0 .036) with an odds ratio of 5.40 (95% confidence interval of 1.120-26.045)., Conclusion: We found that lupus nephritis was the only predictor of severe to critical COVID-19 in SLE.

Objectives: We aimed to estimate what proportion of people with SLE attending UK rheumatology clinics would be categorized as being at high risk from coronavirus disease 2019 (COVID-19) and therefore asked to shield, and explore what implications this has for rheumatology clinical practice., Methods: We used data from the British Society for Rheumatology multicentre audit of SLE, which included a large, representative cross-sectional sample of patients attending UK Rheumatology clinics with SLE. We calculated who would receive shielding advice using the British Society for Rheumatology's risk stratification guidance and accompanying scoring grid, and assessed whether ethnicity and history of nephritis were over-represented in the shielding group., Results: The audit included 1003 patients from 51 centres across all 4 nations of the UK. Overall 344 (34.3%) patients had a shielding score ≥3 and would have been advised to shield. People with previous or current LN were 2.6 (1.9-3.4) times more likely to be in the shielding group than people with no previous LN (P < 0.001). Ethnicity was not evenly distributed between the groups (chi-squared P < 0.001). Compared with White people, people of Black ethnicity were 1.9 (1.3-2.8) and Asian 1.9 (1.3-2.7) times more likely to be in the shielding group. Increased risk persisted after controlling for LN., Conclusion: Our study demonstrates the large number of people with SLE who are likely to be shielding. Implications for clinical practice include considering communication across language and cultural differences, and ways to conduct renal assessment including urinalysis, during telephone and video consultations for patients who are shielding., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Both the herpes zoster virus and suid herpesvirus type 1 (SuHV-1) belong to the Varicellovirus genus of the α-herpesviridae subfamily. They may cause opportunistic infections especially in patients with kidney diseases, varying from latent illness to overt lethality. Under these circumstances, impaired renal function is both the culprit for and victim of the infection. However, fulminant eruption of severe skin herpes zoster in lupus nephritis (LN) patients under prolonged immunosuppressive therapy is rare and even more rarely seen is the SuHV-1 encephalitis in human. Facing the evolution of these rare infections, we hence chose to review the clinical pathogenicity of these two viruses which were cognate in origin but distinct in virulence. As such, we began with the first of the two above viral diseases and proceeded with peculiar renal involvement, unique clinical symptoms and pertinent lethal risk. Of importance, LN was used to exemplify the reciprocally detrimental interactions between impaired renal function and suppressed immune response. Then in a manner similar to the gradient overlay, SuHV-1 encephalitis was discussed focusing on its neurotropic features, specific MRI findings and exclusive test of high throughput sequencing. Our report highlighted novel presentations of the Varicellovirus genus infection by providing a productive multidisciplinary communication with pointed disclosure of the renal involvement. It may therefore be of great medical relevance and educational value for clinicians, especially the unseasoned ones, to foresee and manage similar cases in susceptible patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

A 38-year-old woman, diagnosed as Person Living with Human Immunodeficiency Virus (HIV) on Highly Active Antiretroviral Therapy (HAART) for three years, presented with features of fever, rashes, joint pain, dyspnea and pedal edema. On evaluation, a diagnosis of Systemic Lupus Erythematosus with Lupus Nephritis (LN) triggered by HIV infection was made based on clinical and serological evidence. She was continued on HAART, and immuno-suppressive therapy was co-administered resulting in the resolution of her symptoms. Lupus-like histopathological findings have been reported in patients with HIV-related kidney diseases. This case report is to highlight the co-existence of LN in a patient with HIV infection., Competing Interests: None

Introduction: In contrast to organ transplantation, few studies correlate the monitoring of pp65 antigenemia with a diagnosis of cytomegalovirus (CMV) in patients with systemic lupus erythematosus (SLE)., Objective: To highlight the importance of CMV outside transplantation, we monitored pp65 antigenemia in a series of SLE patients., Methods: From March 2015 to March 2016, SLE patients presenting kidney involvement, fever, and an unclear infection at hospital admission were monitored through pp65 antigenemia. The pp65 antigenemia assay, revealed by immunofluorescence, was correlated with clinical and laboratory findings., Results: We included 19 patients with a suspected unclear infection. A positivity for pp65 antigenemia was found in seven patients (36.8%). The mean age was 33.5 ± 11.2 years, 16 (84%) were females, and 16 (84%) were black. Lymphopenia, anemia, and higher scores of SLEDAI were significantly more common in pp65-positive patients. Five patients received antiviral therapy with ganciclovir. Although receiving specific CMV treatment, one patient died because of suspected CMV disease., Conclusions: Pp65 antigenemia might be relevant in SLE patients, and studies with a greater number of patients are needed in order to establish sensitivity and specificity of pp65 antigenemia in different clinical contexts of SLE patients.

Endogenous retroviruses are implicated in murine lupus nephritis. They provide a source of nephritogenic retroviral gp70-anti-gp70 immune complexes through the production of serum gp70 protein and anti-gp70 autoantibodies as a result of the activation of TLR7. The Sgp (serum gp70 production) loci identified in lupus-prone mice play distinct roles for the expression of different classes of endogenous retroviruses, as Sgp3 regulates the transcription of xenotropic, polytropic and modified polytropic (mPT) viruses, and Sgp4 the transcription of only xenotropic viruses. In the present study, we extended these analyses to a third locus, Sgp5, using BALB/c mice congenic for the NZW-derived Sgp5 allele and also explored the possible interaction of Sgp3 and Sgp4 loci to promote the expression of endogenous retroviruses and serum gp70. The analysis of Sgp5 BALB/c congenic mice demonstrated that the Sgp5 locus enhanced the expression of xenotropic and mPT viruses, thereby upregulating the production of serum gp70. These data indicate a distinct action of the Sgp5 locus on the expression of endogenous retroviruses, as compared with two other Sgp loci. Moreover, comparative analysis of C57BL/6 double congenic mice for Sgp3 and Sgp4 loci with single congenic mice revealed that Sgp3 and Sgp4 acted synergistically to elevate the transcription of the potentially replication-competent Xmv18 provirus and the production of serum gp70. This indicates that the combined effect of three different Sgp loci markedly enhance the expression of endogenous retroviruses and their gene product, serum gp70, thereby contributing to the formation of nephritogenic gp70-anti-gp70 immune complexes in murine lupus., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To determine the significance of hepatitis B virus (HBV)-associated antigen deposition in renal tissue from patients with systemic lupus erythematosus (SLE)., Methods: The medical records of 166 inpatients with lupus nephritis and 384 controls without SLE were analyzed retrospectively. Patients with SLE were classified as positive or negative depending on whether HBV-associated antigen deposition was detected in renal biopsies., Results: HBV-associated antigen deposition was mainly detected in renal tissue from patients with SLE (50.6%), primary renal glomerular disease (20.8%), and allergic purpura (21.7%). It was not detected in renal tissue from patients with diabetic nephropathy, hypertensive nephrosclerosis, thin basement membrane nephropathy, or Alport syndrome. Hepatitis B surface antigen and core antigen were deposited in the mesangial region and vascular loops. The positive group had a significantly higher frequency of IgG, IgA, and IgM deposition than the negative group (53.6% vs 30.5%; p < 0.01). There was no significant difference in the types of lupus nephritis observed between the 2 groups., Conclusion: There was a high prevalence of HBV-associated antigen deposition in renal tissue of patients with SLE by indirect immunofluorescence, which may result mainly from the cross-reactivity with deposited immunoglobulins.

Lupus nephritis is a complication of systemic lupus erythematosus, a heterogeneous autoimmune syndrome involving multiple pathways. Accumulating data from the fields of genetics, clinical science, transcriptomics and basic immunology indicate that antiviral immunity has relevance in the pathogenesis of lupus nephritis. This idea is based on the existence of genetic variants that promote the persistence of nuclear particles in the extracellular space or inside lysosomes. Such nuclear particles mimic viral particles and their RNA or DNA components activate viral nucleic acid recognition receptors in antigen-presenting cells. These autoadjuvant effects of endogenous nucleic acids promote an inappropriate immune interpretation of the nuclear particles during antigen presentation. This process fosters the expansion of autoreactive T cells and B cells, which promotes autoantibody production and immune complex glomerulonephritis. The release of interferon α sets off an antiviral immune response with a coordinated induction of hundreds of antiviral genes both inside and outside the kidney. In this article we summarize the available data indicating that innate immunity triggers antiviral immunity in systemic lupus erythematosus. We also discuss the related implications for innovative therapeutic strategies., (© 2012 Macmillan Publishers Limited. All rights reserved)

The envelope glycoprotein gp70 of endogenous retroviruses implicated in murine lupus nephritis is secreted by hepatocytes and its expression is controlled by Sgp3 (serum gp70 production 3) and Sgp4 loci derived from lupus-prone mice. Among three different endogenous retroviruses (ecotropic, xenotropic and polytropic), xenotropic viruses are considered to be the major source of serum gp70. Although the abundance of xenotropic viral gp70 RNA in livers was up-regulated by the presence of these two Sgp loci, it has not yet been clear whether Sgp3 and Sgp4 regulate the expression of a fraction or multiple xenotropic viruses present in mouse genome. To address this question, we determined the genetic origin of xenotropic viral sequences expressed in wild-type and two different Sgp congenic C57BL/6 mice. Among 14 xenotropic proviruses present in the C57BL/6 genome, only two proviruses (Xmv10 and Xmv14) were actively transcribed in wild-type C57BL/6 mice. In contrast, Sgp3 enhanced the transcription of Xmv10 and induced the transcription of three additional xenotropic viruses (Xmv15, Xmv17 and Xmv18), while Sgp4 induced the expression of a different xenotropic virus (Xmv13). Notably, stimulation of TLR7 in Sgp3 congenic C57BL/6 mice led to a highly enhanced expression of potentially replication-competent Xmv18. These results indicated that Sgp3 and Sgp4 independently regulated the transcription of distinct and restricted sets of xenotropic viruses in trans, thereby promoting the production of nephritogenic gp70 autoantigens. Furthermore, the induced expression of potentially replication-competent xenotropic viruses by Sgp3 may contribute to the development of autoimmune responses against gp70 through the activation of TLR7., (2011 Elsevier Ltd. All rights reserved.)

We have demonstrated that glomerular expression of polyomavirus large T antigen (T-ag) in a binary tetracycline-regulated T-ag transgenic mouse model (i) terminated tolerance for nucleosomes, (ii) released complexes of nucleosomes and T-ag to the microenvironment from dead cells, and (iii) that these complexes bound induced anti-nucleosome antibodies and finally (iv) that they associated with glomerular membranes as immune complexes. This process may be relevant for human lupus nephritis, since productive polyomavirus infection is associated with this organ manifestation. Here, we compare nephritis in the T-ag transgenic mouse with nephritis in human SLE. Glomerular sections were analysed by transmission electron microscopy, immune electron microscopy (IEM) and by co-localization IEM and TUNEL IEM assays to compare morphological changes, composition of immune complexes and formation of nucleosome-T-ag complexes. Affinity of nucleosome-T-ag complexes for glomerular collagen IV and laminin was determined by surface plasmon resonance (SPR). Analyses revealed electron dense structures in both human and murine kidney samples. These EDS were shown to contain T-ag, DNA and histones, indicating that extra-cellular chromatin may originate from polyomavirus infected cells in human kidneys. SPR analyses demonstrated high affinity of nucleosomes and nucleosome-T-ag complexes for collagen IV and laminin. Complexes of nucleosomes, T-ag and anti-T-ag and anti-dsDNA antibodies bind glomerular membranes and contribute to the evolution of lupus nephritis in human SLE.

Polyomavirus BK (BKV) reactivation can occur in immunodeficient patients. Few studies on BKV infection in patients with systemic lupus erytematosus (SLE) nephritis are available. Aim of this study was to analyse the prevalence of BKV infection by quantifying viral load and to investigate the association with clinical and histological parameters indicating duration, type and activity of SLE.BKV-DNA was evaluated by polymerase chain reaction in serum (sBKV) and urine (uBKV) specimens from 40 patients with SLE nephritis and 29 healthy controls. Renal function, urinary activity, clinical index of SLE activity [SLE Disease Activity Index (SLEDAI) score], CD4+/CD8+ ratio, histological classes and duration of SLE nephritis were compared according to the BKV-DNA-positivity.sBKV was present in 15% of SLE patients and in 13.8% of controls; uBKV in 32% of SLE patients and in 17.2% of controls. There was no significant difference in terms of kidney function, urinary activity, SLEDAI score, presence of anti-dsDNA antibodies, CD4+/CD8+ ratio and BKV viremia and/viruria, as well as there was no significant correlation between SLEDAI score, anti-dsDNA antibodies titers and median viral load. Duration of nephropathy tended to be shorter in patients with BKV viremia and/or viruria; proteinuria/creatininuria ratio tended to be higher in patients with positive sBKV and uBKV. BKV-DNA-positivity tended to be more frequent in patients treated with an immunosuppressive agent versus those on steroid treatment. Reactivation of BKV infection can occur in patients with SLE, although prevalence data do not significantly differ from those obtained in the control group. The trend toward an association between BKV infection and degree of proteinuria and less duration of SLE nephritis could indicate a major susceptibility to develop BKV infection in more active phases of the disease. The role of BKV reactivation in terms of clinical parameters and histological pattern, as well as the role of therapeutic protocols in the onset of BKV reactivation and, conversely, the therapeutic implication of BKV reactivation in SLE patients remain to be defined and should be addressed in further studies on a larger number of patients.

Lupus nephritis develops from a combination of genetic and environmental factors such as microbial infection. A role for microbial nucleic acids (e.g., via nucleic acid-specific Toll-like receptors [TLR]) was hypothesized, in this context, because microbial nucleic acids can trigger multiple aspects of autoimmunity in vitro and in vivo. Eight-week-old MRL(lpr/lpr) and MRL wild-type mice received an injection of pI:C RNA (ligand to TLR-3), imiquimod (ligand to TLR-7), or CpG-DNA (ligand to TLR-9) on alternate days for 2 wk. Only CpG-DNA triggered the onset of lupus nephritis in MRL(lpr/lpr) mice, as defined by diffuse proliferative glomerulonephritis associated with glomerular IgG and complement C3 deposition, proteinuria, and glomerular macrophage infiltrates. None of the compounds caused DNA autoantibody production or glomerulonephritis in MRL wild-type mice. The role of CpG-DNA to trigger lupus nephritis in MRL(lpr/lpr) mice was found to relate to its potent immunostimulatory effects at multiple levels: B cell IL12p40 production, B cell proliferation, double-stranded DNA autoantibody secretion, and dendritic cell IFN-alpha production. The induction of lupus nephritis by CpG-DNA is motif specific and could be prevented by co-injection of inhibitory DNA. In summary, among the ligands tested, CpG-DNA triggers lupus nephritis in genetically predisposed hosts. These data support the concept that systemic lupus erythematosus is triggered by pathogens that release CG-rich DNA.

A 77-year-old Japanese man with a 14-year history of human T-cell lymphotropic virus type I-associated myelopathy developed pancytopenia, proteinuria, renal dysfunction, and hypocomplementemia. Antinuclear antibody and anti-double-stranded DNA antibody test results were positive, and circulating immune complexes were detected. A renal biopsy showed diffuse and global mesangiocapillary proliferation with extensive subendothelial deposits. Immunofluorescence microscopy showed strong granular staining for immunoglobulins and complements in the mesangium and along capillary walls. Electron microscopy showed numerous mesangial and subendothelial electron-dense deposits. From these findings, systemic lupus erythematosus and diffuse global lupus nephritis were diagnosed. This is a rare case of a patient developing lupus nephritis during the long-term course of human T-cell lymphotropic virus type I-associated myelopathy.

How viral infections trigger autoimmunity is poorly understood. A role for Toll-like receptor 3 (TLR3) was hypothesized in this context as viral double-stranded RNA (dsRNA) activates dendritic cells to secrete type I interferons and cytokines that are known to be associated with the disease activity in systemic lupus erythematosus (SLE). Immunostaining of nephritic kidney sections of autoimmune MRL(lpr/lpr) mice revealed TLR3 expression in infiltrating antigen-presenting cells as well as in glomerular mesangial cells. TLR3-positive cultured mesangial cells that were exposed to synthetic polyinosinic-cytidylic acid (pI:C) RNA in vitro produced CCL2 and IL-6. pI:C RNA activated macrophages and dendritic cells, both isolated from MRL(lpr/lpr) mice, to secrete multiple proinflammatory factors. In vivo, a single injection of pI:C RNA increased serum IL-12p70, IL-6, and IFN-alpha levels. A course of 50 microg of pI:C RNA given every other day from weeks 16 to 18 of age aggravated lupus nephritis in pI:C-treated MRL(lpr/lpr) mice. Serum DNA autoantibody levels were unaltered upon systemic exposure to pI:C RNA in MRL(lpr/lpr) mice, as pI:C RNA, in contrast to CpG-DNA, failed to induce B cell activation. It therefore was concluded that viral dsRNA triggers disease activity of lupus nephritis by mechanisms that are different from those of bacterial DNA. In contrast to CpG-DNA/TLR9 interaction, pI:C RNA/TLR3-mediated disease activity is B cell independent, but activated intrinsic renal cells, e.g., glomerular mesangial cells, to produce cytokines and chemokines, factors that can aggravate autoimmune tissue injury, e.g., lupus nephritis.

A role for retroviruses in human systemic lupus erythematosus (SLE) and in mouse lupus models such as the New Zealand Black and White mice (NZB/W) strain has been postulated. This study compared the gene profile of nephritic NZB/W kidney with nondiseased NZW controls. The most highly upregulated gene (5.5-fold) hybridized with an expressed sequence tag on a cDNA microarray, which was sequenced and found to correspond with an endogenous murine retrovirus related to the Duplan strain (EDV, L08395). NZB/W kidney contained the full-length 4.2-kb EDV transcript. By 4 wk of age in NZB/W mice, an age preceding renal histologic disease, the EDV transcript was more than threefold increased relative to NZB or NZW control strains. This upregulated expression tended to fall with progression of renal histologic disease. By in situ hybridization, the EDV transcript was highly expressed in tubules of NZB/W mice. There was also upregulated expression of EDV transcript in NZB/W lung and brain, sites of inflammation in this strain, but not in spleen or liver. Thus, using microarrays, the most highly expressed gene in mouse lupus nephritis corresponded to an endogenous retrovirus. This retroviral transcript was highly expressed in the kidneys of lupus mice and tended to decline with advancement of disease. The remarkable upregulation of the EDV transcript only in the setting of active disease suggests this transcript is involved in inflammatory disease.

Simian virus 40 (SV40), a monkey polyomavirus that is believed to have entered the human population through contaminated vaccines, is known to be renotropic in simians. If indeed SV40 is endemic within the human population, the route of transmission is unknown. It was therefore hypothesized that SV40 might be renotropic in humans and be detected more frequently in samples obtained from patients with kidney diseases. This study found that typical polyomavirus cytopathic effects (CPE) were present and SV40 T antigen was detected in CV-1 cells cultured with peripheral blood mononuclear cells (PBMC) or urinary cells obtained from patients with kidney disease and healthy volunteers. DNA sequences homologous to the SV40 viral regulatory genome were detected by PCR in urinary cells from 15 (41%) of 36 patients with focal segmental glomerulosclerosis (FSGS), 2 (10%) of 20 patients with other kidney diseases, and 1 (4%) of 22 healthy volunteers (FSGS compared with other glomerular disease, P < 0.02; FSGS compared with healthy volunteers, P = 0.003). SV40 viral regulatory region genome was detected from PBMC at similar frequencies in patients with FSGS (35%), other glomerular diseases (20%), and healthy volunteers (22%). SV40 genome was detected by PCR in kidney tissues from 17 (56%) of 30 of patients with FSGS and 4 (20%) of 20 patients with minimal change disease and membranous nephropathy (P < 0.01). Considerable genetic heterogeneity of the viral regulatory region was detected, which argues against laboratory contamination. SV40 genome was localized to renal tubular epithelial cell nuclei in renal biopsies of patients with FSGS by in situ hybridization. This study demonstrates for the first time that human kidney can serve as a reservoir for SV40 replication and that SV40 may contribute to the pathogenesis of kidney disease, particularly FSGS.

We compared the clinicopathologic features of 22 patients with hepatitis B virus-related membranous nephropathy, all with detectable glomerular hepatitis B e antigen, and of 26 patients with lupus nephritis class V. Both groups of patients similarly presented with heavy proteinuria or nephrotic syndrome; however, the patients with hepatitis B virus-related membranous nephropathy, who were predominantly male, did not have the extrarenal manifestations and autoantibodies seen in systemic lupus erythematosus. The glomerular lesions in both clinical entities were similar and at times indistinguishable, demonstrating polyclonal immunoglobulins and polytypic complements in similar subepithelial ultrastructural distribution. No morphologic feature, single or combined, carrying a high positive predictive value for the diagnosis of either nephritis was identified. Lesions such as hematoxyphil bodies and fingerprint dense deposits, distinctive of systemic lupus erythematosus, were rarely found. At the time of biopsy, when systemic lupus erythematosus is not clinically suspected, the diagnosis between hepatitis B virus-related membranous nephropathy and lupus nephritis may be difficult or impossible to differentiate, especially in geographic areas where both lupus nephritis and hepatitis B surface antigen carriers are common. This study focused on the use of specific monoclonal antisera to detect glomerular hepatitis B virus antigens, which contribute to the diagnosis of hepatitis B virus-related nephritis.

It has long been suggested that retroviral infection may play a role in the pathogenesis of autoimmune rheumatic disease. Particles resembling retroviruses have been reported in tissue from patients with Sjögren's syndrome, lupus and rheumatoid arthritis, and molecular mimicry between retroviral antigens and host proteins has been proposed as a mechanism of induction of autoimmunity. Since 1980, four distinct human infectious retroviruses have been discovered, HTLV-I, HTLV-II, HIV-1 and HIV-2. We recently cloned part of a new human retrovirus genome, designated human retrovirus-5 (HRV-5) and demonstrated that this is not endogenous and is therefore a novel infectious retrovirus. Because symptoms resembling arthritis, polymyositis and Sjögren's syndrome occur in individuals infected with HTLV-I and HIV-1, we investigated the possibility that HRV-5 was associated with idiopathic rheumatic disease. Using nested PCR, HRV-5 we demonstrated that proviral DNA was present in approximately 50% of synovial samples of arthritic joints and was also found in over 10% of blood samples of patients with rheumatoid arthritis and systemic lupus erythematosus. HRV-5 proviral DNA was not detectable in affected tissues of autoimmune diseases and was found in only one of over 200 tissues taken at autopsy from non-rheumatoid patients. Sequence analysis of the amplified viral segment showed genetic variation between samples with maintenance of the open reading frame typical of a replicating infectious retrovirus. Thus HRV-5 appears to be a human retrovirus found with a very low genome copy number in most tissues, but which is increased to detectable levels in inflamed joints and blood from patients with rheumatic disease. Whether HRV-5 is aetiologically important in these diseases remains to be determined., (Copyright 1999 Academic Press.)

Relationships between viruses and autoimmune diseases such as systemic lupus erythematosus (SLE) are still elusive. Recent reports demonstrated the association of some viral infections with peculiar clinical events in the general population, such as cytomegalovirus (CMV) with arterial damage and Parvovirus B19 (PV-B19) with hematologic abnormalities. We planned to look for this kind of viral imprinting in SLE, hypothesizing that traces of specific features of some viral infections might be found in some subsets of seropositive SLE patients. In 60 SLE patients recruited at our nephrologic center, serology for CMV, PV-B19, Epstein-Barr virus viral capsid antigen (EBV-VCA), Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr virus early antigen (EBV-EA) was performed. chi2 and ANOVA were employed to compare the frequency and titers of antiviral antibodies in SLE patients with groups of transplant, hemodialysis and blood donor subjects. chi2, Fisher's test, Bonferroni and Scheffe's test were employed to compare the different biochemical/clinical features between seropositive and seronegative SLE patients. Univariate and multivariate analysis (logistic regression models) were employed to evaluate the odds ratio (OR) of different risk factors for vascular events (including Raynaud's phenomenon, deep venous thrombosis) and hematologic abnormalities (including severe anemia, leukopenia and thrombocytopenia). Anti-CMV (82%), anti-PV-B19 (60%), anti-EBV-VCA (92%) and EBV-EA (45%) IgG antibodies were frequent in SLE, with higher prevalence in comparison with the blood donor group and higher titers in comparison with transplant and hemodialysis groups. CMV seropositivity was a highly significant risk factor for Raynaud's phenomenon (OR +alpha in univariate and multivariate analysis = 13.51 using a correction of 0.5 in case of a zero event), but not for venous vascular events (OR = 1.31). An increased though not significant risk factor was found for antiphospholipid antibodies (OR = 2.71, p = 0.19), while the presence of nephrotic syndrome during the follow-up was a significant protective factor (OR = 0.15, p = 0.035). There was no significantly increased OR for PV-B19 seropositivity in cases with severe anemia (OR = 2.09, p = 0. 29). No significant associations were found with the status of EBV reactivation. In conclusion, our results support the hypothesis that viral infection may imprint the course of SLE leading to specific clinical subsets (i.e. CMV and 'vascular' SLE, with more frequent Raynaud's phenomenon and a less frequent typical histological renal picture responsible for nephrotic syndrome). Further prospective studies are justified to validate these correlations, mainly dealing with associations between acute viral infections and vascular events, thus eventually leading to a better understanding of mutual relationships between viruses and SLE.

Background: Relationships between viral infections and autoimmune diseases are complex and debated: on the one hand, patients with LES are particularly prone to develop viral infections, on the other, some virus are thought to play a role both in triggering the onset of the immunologic disease and in conferring peculiar clinical features to flare-ups., Methods: This study has drawn an epidemiologic profile of viral pathology from Epstein Barr virus, Parvovirus B 19 and Cytomegalovirus in 60 patients with LES followed-up for a period ranging from 13 to 340 months (on average 158 months)., Results: Cytomegalovirus seropositivity has turned out to be a strong, statistically significant risk factor for vascular accidents and especially for peripheral ones, such as Raynaud phenomenon, ulcers and distal necrosis (OR = 6.5 IC = 0.7-7.9* p = 0.037)., Conclusions: Although Cytomegalovirus seropositivity is associated with an increased frequency of LAC/ACA, its relationship with vascular events does not seem to be mediated through such antibodies, apparently acting as an independent risk factor which also works in LAC/ACA negative patients. Parvovirus B 19 seropositivity has turned out to be the only increased risk factor for the development of anemia, although not reaching statistical significance, whereas Epstein Barr seropositivity does not appear to influence clinical features significantly.

The optimal therapy for pure membranous lupus nephritis (MLN) with nephrotic syndrome remains controversial. While the risk of progressive renal deterioration may be small, persistent heavy proteinuria leads to the complications of oedema, hypoalbuminaemia, hyperlipidaemia, hypercoagulability, and venous thrombosis. We examined prospectively the efficacy and tolerability of a sequential immunosuppressive regimen in a cohort of 20 patients with nephrotic syndrome due to pure MLN (WHO Class Va and Vb). Initial therapy comprised prednisolone (0.8 mg/kg/d p.o.) and cyclophosphamide (2-2. 5 mg/kg/d p.o.). Prednisolone dosage was gradually tapered to 10 mg/d at 6 months, when cyclophosphamide was replaced by azathioprine (2 mg/kg/d p.o.) as maintenance therapy. Within 12 months of therapy 11(55%) patients had complete remission (CR), 7(35%) patients achieved partial remission (PR) (proteinuria reduced from 6.2+/-4.0 to 2.0+/-1.7 g/24 h, P<0.01), and 2 patients failed to respond. Improvements in proteinuria and serum albumin level were observed after 3-6 months of treatment. Non-responders had lower baseline serum albumin compared to complete responders. Renal function remained stable during follow-up for 73.5+/-48.9 months. 8 patients had disease relapse at 47+/-15 months. Early complications (