Short CommunicationVirus discovery in chronic inflammatory demyelinating polyneuropathy
Introduction
Chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain-Barré syndrome (GBS) are both immune-mediated peripheral neuropathies, causing weakness and sensory deficits. CIDP usually exhibits a slowly progressive, or relapsing remitting course whereas GBS has an acute onset and monophasic course.(van den Bergh et al., 2010; Van der Meche et al., 2001) Around 18% of CIDP patients have an acute onset of CIDP, mimicking GBS.(Eftimov and van Schaik, 2013) The events triggering and/or sustaining the deregulated auto-immune response underlying CIDP are unknown.(Mathey et al., 2015) In GBS, molecular mimicry stands centrally in the pathogenesis, in which an infection triggers the immune system to attack components of the peripheral nerve.(Wijdicks and Klein, 2017) Infection with Campylobacter jejuni is the most known bacterial infection described to trigger GBS, however viruses, like cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella-zoster virus, herpes simplex virus, hepatitis viruses, influenza, HIV-1, dengue virus and Zika virus also have been implicated.(Jacobs et al., 1998; Barbi et al., 2018; van den Berg et al., 2014; Hao et al., 2019; Brannagan 3rd and Zhou, 2003) Similar to GBS, an infectious event may play a role in the onset of CIDP. However, unlike GBS, no infection has yet been consistently linked to the onset of CIDP. To our knowledge, no systematic studies using Virus Metagenomics in CIDP patients have been performed.
VIDISCA - next generation sequencing (NGS) is such a Virus Metagenomics technique that is able to read the genomic RNA or DNA in particles of known and unknown viruses in a clinical sample.(de Vries et al., 2011; de Vries et al., 2012; van Zeggeren et al., 2021) The aim of this explorative study is to chart the virome of CIDP patients by means of VIDISCA-NGS. We hypothesize that viruses may be responsible for triggering and/or sustaining the deregulated immune response in some CIDP patients, especially those with an acute onset.
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Patients
CIDP patients were prospectively included from 2014 to 2017. All patients were seen at a tertiary referral center for inflammatory neuropathies, Amsterdam UMC, the Netherlands. We included CIDP patients fulfilling the definite, probable or possible EFNS/PNS criteria or the clinical criteria and two or more EFNS/PNS supportive criteria.(van den Bergh et al., 2010) The study was approved by the Medical Ethical Committee of the Academic Medical Centre and was in accordance with Declaration of
Results
A total of 47 CIDP patients were included (mean age 60 years ±14.6); 28 (60%) newly diagnosed, seven (15%) after a relapse and 12 (26%) patients were on maintenance IVIg treatment at time of blood sampling (Table 1). Nine out of 28 (32%) newly diagnosed patients presented with an acute onset CIDP, with a median disease duration to sampling of two months (range 1–8 months). The other 19 patients presented with a more slowly progressive form, with a median disease duration to sampling of
Discussion
We found serum samples positive for anellovirus, a highly prevalent and non-pathogenic virus, in 11% of CIDP patients and in 28% of the healthy age matched controls. Based on the prevalence of anellovirus described in previous research, this is not relevant.(Bendinelli et al., 2001; Maggi and Bendinelli, 2010) One sample tested positive for GBVC, another common nonpathogenic infection (Giret and Kallas, 2012) and one for Parvovirus B19. Parvovirus B19 is known to cause erythema infectiosum and
Conclusion
We did not find pathogenic viruses with VIDISCA-NGS in blood or CSF of CIDP patients. Therefore, a (persistent) viral infection sustaining the auto-immune response in CIDP seems unlikely. Antecedent viral infections triggering CIDP cannot be ruled out given the small numbers of CIDP patients with acute onset and because the virus may have been cleared or be below detection levels at the time clinical symptoms occurred.
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