cell biochemistry and function

Cell Biochem Funct 2007; 25: 639641.

Published online 18 August 2006 in Wiley InterScience
(www.interscience.wiley.com) DOI: 10.1027/cbf.1364

Parvovirus B19 and immune disorders

Agostino Pugliese1*, Tiziana Beltramo1, Donato Torre2 and Dario Roccatello3
1
Department of Medical and Surgical Sciences, Clinical Microbiology University of Turin, Amedeo di Savoia Hospital,
Turin, Italy
2
Section of Infectious Diseases, General Hospital, Cittiglio, Varese, Italy
3
Department of Medicine and Experimental Oncology, Clinical Pathology, University of Turin, Turin, Italy

Parvovirus B19 (PVB19) is the causative agent of erythema infectiosum and sometimes the infection is correlated with severe
haematological complications, or in pregnancy to fetalis hydrops. Moreover some authors suggest an infection involvement
in some autoimmune diseases. To this purpose we evaluated seroprevalence for PVB19 in following the autoimmune or
dysreactive pathologies: systemic lupus erythematosus (SLE), cryoglobulinemia, idiopathic systemicANCA associated
vasculitis, rheumatoid arthritis (RA). In the case of LES, 31/42 patients were positive for PVB19 versus 21/42 of blood
donors, as controls subjects (73.8% vs. 50%; signicant difference for p < 0.05), moreover a signicant difference for
p < 0.001 was detected comparing mean titre values of IgGs against PVB19 of two groups (UI 1.94
0.90 vs. 1.24
0.80).
In contrast no signicant differences were found in the case of percent seropositivity of cryoglobulinemic subjects
(37/57 64.9%, the majority of whom were HCV) in comparison with the control group (50%). However mean units
index (UI) was 1.63
0.81; p 0.019 versus the control group. Similar result, with regard to the percentage of seropositivity,
was found for vasculitis (9/17 52.9%). The data reported here can conrm a possible correlation between PVB19 prior
infection and LES and also suggest possible implications in the case of cryoglobulinemia. In fact, most of our patients were
affected by a nephropathic or systemic form of HCV cryoglobulinemia and the presence of other infective cofactors could
be suggestive in the evolution of this clinical situation. Copyright # 2006 John Wiley & Sons, Ltd.

key words Parvovirus B19; systemic lupus erythematosus; cryoglobulinemia; vasculitis; rheumatoid arthritis

INTRODUCTION the presence of autoantibodies of rheumatoid factor

Parvovirus B19 (PVB19) is a common exanthematous
infection that affects children, especially in winter and
spring months, but can occur also in adults and is
particularly serious during pregnancy, often involving
the foetuses too.1 In particular it was demonstrated
that PVB19 is the causative agent of erythema
infectiosum and may produce a transient aplastic
crisis in predisposed patients and has been associated
with hydrops fetalis, arthritis and chronic anaemia.2,3
Moreover different viral infections, such as Epstein-
Barr virus, Cytomegalovirus and Parvovirus B19 have
been correlated with rheumatoid arthritis (RA).4 Also
* Correspondence to: A. Pugliese, Department of Medical and
Surgical Sciences, Clinical Microbiology, University of Turin,
Amedeo di Savoia Hospital, Corso Svizzera 16410149 Torino,
Italy. Tel: 390114393865. Fax: 390114393882.
E-mail: agostino.pugliese@unito.it
type, and anti-nuclear antibodies during PVB19
primary infection has been reported.57 In addition
manifestations of rheumatoid polyarthritis following
PVB19 infection have been described.8 However, the
progression to authentic RA seems to be exceptional.9
In the case of systemic lupus erythematosus (SLE)
the correlation between PVB19 infection was con-
sidered by different authors as more or less
probable.1013 Analogously the role of PVB19
infection on other connective diseases such as Sjogren
syndrome (SS),14 and systemic dermatosclerosis,2,15
or cryoglobulinemia16 is still discussed.
In contrast, Seve et al.3 think that only in rare cases
can PVB19 act as a trigger of RA, SLE or vasculitis.
In order to clarify the role of a PVB19 previous
infection on some autoimmune or dysreactive diseases
we analysed the sera of 131 adult patients affected by
autoimmune pathologies or diseases induced by
immune dysregulation in comparison with the sera

Received 11 April 2006

Revised 5 June 2006
Copyright # 2006 John Wiley & Sons, Ltd. Accepted 29 June 2006
640 a. pugliese
of 42 healthy subjects (blood donors) for search of
anti-PVB19 IgGs by ELISA test.
MATERIALS AND METHODS
Serological study of anti-PVB19 specic antibodies
was performed on the following sera:
42 from SLE patients;
57 from cryoglobulins presenting patients;
17 from patients affected with vasculitis;
6 from patients presenting anti-phospholipid
antibodies;
6 from RA patients, of whom 2 were affected also
with Sjogren syndrome (SS);
3 from SS affected patients;
42 sera of healthy adults used as controls, obtained
from a population of blood donor subjects.
Sera were frozen at 208C until analysis.
Specic IgGs were detected using an ELISA test
(PVB19 IgG antibodies ELISA, DRG-NOVUM
Branch Lab., Dietzenbach, Germany). The titres were
expressed as units index (UI) values
Patient mean absorbance value
UI :
Cut-off control mean absorbance value
The cut-off is a preparation formulated by the
manufacturer of the diagnostic kit to give the optimum
differentiation between negative and positive sera.
Statistical analysis was performed by ANOVA and
by Students t-test when appropriate. P values < 0.05
were considered signicant.
RESULTS
In the case of 42 SLE patients evaluated (mean
age 40.7
12.9 years of whom 75.6% were women)
the percentage of seropositivity for PVB19 was 73.8%
(31/42) versus 50% of the controls (21/42; signicant
difference for p < 0.05) with UI mean of 1.94
0.90
versus 1.24
0.80 (signicant difference for
p < 0.001). Moreover no signicant differences were
found between men and women in the group analysed.
The mean age of blood donors evaluated was
39.2
14.5 years.
In the case of the 57 cryoglobulinemic patients, 54
of them were HCV (73.7% women) having a mean
age of 61.6
12.3 years. The percentage of positivity
for PVB19 was 64.9% (37/57). Considering this value,
no signicant differences were detected in comparison
with the control group. However, UI mean value was
Copyright # 2006 John Wiley & Sons, Ltd.
ET AL.
respectively 1.63
0.81 versus 1.24
0.80 of the
controls (signicant difference for p 0.019).
In the case of 17 vasculitis studied, a seropositivity
for PVB19 of 52.9% (9/17) was observed with mean
UI of 1.55
0.97, but no signicant difference
compared to the control group was found. Similar
results were obtained analysing the small group of six
subjects presenting only anti-phospholipid antibodies.
Among six patients suffering from RA, four were
seropositive for PVB19 (two were also affected with
SS) and mean UI was 1.7
0.93 (no signicant
difference in comparison with the control), besides
among three patients affected only with SS, one
presented signicant values of anti-PVB19 antibodies
and the whole mean UI was 1.28
1.00.
Table 1 summarizes the data corresponding to SLE,
cryoglobulinemia, vasculitis and RA.
DISCUSSION
Parvovirus B19 is responsible of many clinical
manifestations; erythema infectiosum, haemolytic
anaemia with aplastic crisis and hydrops fetalis are
the best known. Moreover in young adults polyar-
thritis often complicates the primary infection.12 In
addition, the infection has been correlated with
different autoimmune or dysreactive diseases such
as RA, SLE, vasculitis, systemic sclerosis of skin,2,12
focal segmental glomerulosclerosis or immune com-
plex-induced glomerulonephritis17 and less probably
cryoglobulinemia.16
Our data demonstrate a signicant correlation
between seropositivity for PVB19 and SLE both in
the case of positivity percentage and in that of IgGs
anti-PVB19 mean levels. In contrast, in the case of
cryoglobulinemia and vasculitis no signicant corre-
lations were found, with regard to the percentage of
seropositivity, but for the former case signicant
correlations were found regarding the mean UI values.
In fact, cryoglobulinemic subjects showed higher UI
mean levels of IgGs against PVB19, than controls.
These patients were almost all HCV and had renal or
Table 1. Percentage of seropositivity for PVB19 and mean UI in
some autoimmune or dysreactive diseases
Disease Positive cases Percentage UI (mean
SD)
SLE 31/42 73.8% 1.94
0.90
Cryoglobulinemia 37/57 64.9% 1.63
0.81
Vasculitis 9/17 52.9% 1.55
0.97
RA 4/6 66.7% 1.70
0.93
Healthy subjects 21/42 50% 1.24
0.80

Signicant difference among the groups for p 0.008 by ANOVA.
Cell Biochem Funct 2007; 25: 639641.
DOI: 10.1002/cbf
 parvovirus and autoimmunity
systemic involvement, and because the determinants
of HCV cryoglobulinemia clinical evolution are
unknown,18 the possible intervention of other viral
cofactors is suggestive in this case. However, Cacoub
et al.16 think that only acute, but non-prior cleared up
infection may be responsible for cryoglobulinemia.
Moreover it has been reported that vasculitis is also
correlated with PVB19 occurring during acute
Parvovirus disease and not from long-term infection.19
In addition, we emphasize that our patients did not
have PVB 19 actual infection.
In conclusion, our study, although performed on a
small number of patients, seems to suggest that only in
the case of patients suffering from SLE a correlation
with a prior infection with PVB19 is very probable. In
fact, none of our patients presented signs of acute
PVB19 infection or in the anamnesis was reported a
recent previous febrile infection. Moreover a possible
involvement of PVB19 prior infection on HCV
cryoglobulinemia clinical evolution is also suggested.
ACKNOWLEDGEMENTS
This study is supported by Italian Ministry of Public
Education, of University and Scientic Research.
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Cell Biochem Funct 2007; 25: 639641.
DOI: 10.1002/cbf