Human parvovirus B19 infection: its relationship with systemic lupus erythematosus

doi:10.1016/S0049-0172(99)80016-X

Seminars in Arthritis and Rheumatism

Volume 28, Issue 5, April 1999, Pages 319-325

https://doi.org/10.1016/S0049-0172(99)80016-X Get rights and content

Abstract

Objectives:

The clinical presentation and outcome of four cases of human parvovirus-B19(HPV-1319) infection, initially diagnosed as systemic lupus erythematosus (SLE), were reviewed and compared with similar cases previously reported in the literature. The relationship between HPV-1319 infection and SLE is discussed.

Methods:

The medical records of four patients with documented HPV B19 infection, initially diagnosed as SLE, were reviewed and studied in detail. A Medline search from 1985 to 1997 was performed to identify other cases reported in the literature in which a relationship between HPV B19 and SLE had been identified in both adults and children.

Results:

In all of our cases, the clinical findings (fever, rash, arthritis and malaise) and hematologic data (leukopenia, thrombocytopenia, anemia, presence of autoantibodies, hypocomplementemia, etc.) had initially suggested a diagnosis of juvenile SLE. Subsequently, evidence of HPV-B19 infection at the time of clinical presentation was ascertained. In three of these cases, the disease course was self-limiting with complete clinical remission and normalization of hematologic abnormalities within 18 months; one case, however, had persistent disease activity and repeated exacerbations.

Conclusions:

The occurrence of HPV-B19 infection has been documented in patients with SLE, in particular in relation to disease onset. Similarities in clinical and immunological features of viral infections and SLE at presentation may hinder the differential diagnosis between these two conditions. The family history, a self-limiting disease course and certain disease specific clinical aspects may help the pediatrician formulate an accurate diagnosis. In our patients, HPV-B19 infection may have mimicked the onset of SLE in three cases, but triggered the disease in one.

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Acute Parvovirus B19 (PVB19) infection is responsible for erythema infectiosum in children and non-specific polyarthralgias in immunocompetent adults associated with skin lesions and rarer manifestations (hepatic, neurological, cardiac or nephrological). In immunocompromised patients, cytopenias are more frequent and in some cases, viremia persists and is responsible for PVB19 chronic infection. PVB19 is responsible for pure red cell aplasia during chronic hemolytic diseases. Acute PVB19 infection is a differential diagnosis of some autoimmune diseases and has been suspected to be a trigger for some autoimmune diseases because of its ability to promote the emergence of autoimmune markers. Mechanisms of molecular mimicry, induction of apoptosis and activation of enzymes have been demonstrated, explaining in part the production of autoantibodies during infection. However, the demonstration of a causal relationship in the triggering of autoimmune disease remains to be done. This review provides a synthesis of the PVB19 infection clinical data in adults with a particular focus on these links with autoimmunity.
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Up-regulation of epithelial Na<sup>+</sup> channel ENaC by human parvovirus B19 capsid protein VP1
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Clinical disorders caused by parvovirus B19 (B19V) infection include endothelial dysfunction with cardiac ischemia. The virus is effective in part by lysophosphatidylcholine-producing phospholipase A2 (PLA2) activity of B19V capsid protein VP1. Mechanisms compromising endothelial function include up-regulation of amiloride sensitive epithelial Na⁺-channel ENaC leading to endothelial cell stiffness. Regulators of ENaC include ubiquitin-ligase Nedd4-2. The present study explored whether VP1 modifies ENaC-activity.
cRNA encoding ENaC was injected into Xenopus oocytes without or with cRNA encoding VP1. Experiments were made with or without coexpression of Nedd4-2. ENaC activity was estimated from amiloride (50 μM) sensitive current.
Injection of cRNA encoding ENaC into Xenopus oocytes was followed by appearance of amiloride sensitive current, which was significantly enhanced by additional injection of cRNA encoding VP1, but not by additional injection of cRNA encoding PLA2-negative VP1 mutant (H153A). The effect of VP1 on ENaC was mimicked by treatment of ENaC expressing oocytes with lysophosphatidylcholine (1 μg/ml). The effect of VP1 and lysophosphatidylcholine was not additive. ENaC activity was downregulated by Nedd4-2, an effect not reversed by VP1.
The B19V capsid protein VP1 up-regulates ENaC, an effect at least partially due to phospholipase A2 (PLA) dependent formation of lysophosphatidylcholine.
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Citation Excerpt :
Cases of histiocytic necrotizing lymphadenitis (Kikuchi disease) associated with PVB19 infection also constitute indirect evidence in favour of this hypothesis: massive lymph node necrosis could release large quantities of nuclear and cellular material [90,91]. The subsequent course over one or two weeks may correct a premature diagnosis of SLE [81,92–94], which, in any case, requires the presence of chronic symptoms to formally establish the diagnosis. However, several cases of persistence of symptoms for several months (or years) independently of viraemia have suggested the possible role of viral infection as a triggering factor in the pathogenesis and/or exacerbation of SLE.
A number of arguments support the role played by PVB19 in autoimmunity, in the broad sense of the term essentially derived from numerous clinical case reports and/or small series over the past 20–30 years in the medical literature. PVB19 can induce a very broad spectrum of autoantibody production, especially including: anti-soluble nuclear antigen antibodies, antiphospholipid antibodies anti-native DNA antibodies, antilymphocyte antibody, anticardiolipin antibodies, antinuclear antibodies and rheumatoid factor. Notably acute PVB19 infection can mimic or stimulate autoimmune systemic diseases as rheumatoid arthritis or systemic lupus erythematosus. However, at the present time, there is no formal scientific evidence demonstrating a direct role of PVB19 in autoimmunity, bearing in mind that there are also no formal arguments against it. Further large studies are needed to understand the eventual role of PVB19 in autoimmune diseases.
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Human parvovirus B19 infection: its relationship with systemic lupus erythematosus

Abstract

Objectives:

Methods:

Results:

Conclusions:

J Pediatr

Semin Arthritis Rheum

Lancet

Systemic lupus erythematosus: cellular immunology

Outbreak of aplastic crisis in sickle cell anemia with parvovirus-like agent

Lancet