Antibody to parvovirus B19 nonstructural protein is associated with chronic arthralgia in patients with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract

(by real-time PCR). CFS/ME patients and normal blood donors had a similar B19 seroprevalence (75 % versus 78 %, respectively). Eighty-three CFS patients (41.5 %) as compared with fourteen (7 %) normal blood donors tested positive for anti-B19 NS1 IgG (x 2 564.8; P,0.0001; odds ratio59. 42,. Of these 83 patients, 61 complained of chronic joint pain, while 22 did not. Parvovirus B19 DNA was detected in serum of 11 CFS patients and none of the controls by Taqman real-time PCR (x 2 59.35, P,0.002). Positivity for anti-B19 NS1 IgG was associated with higher expression levels of the human CFS-associated genes NHLH1 and GABPA. As NS1 antibodies are thought to indicate chronic or severe courses of B19 infection, these findings suggest that although the seroprevalence of B19 in CFS patients is similar to controls, the immune control of the virus in these patients may not be efficient. INTRODUCTIONChronic fatigue syndrome/myalgic encephalomyelitis (CFS/ ME) is a disease characterized by severe and debilitating fatigue, sleep abnormalities, impaired memory and concentration, and musculoskeletal pain (Fukuda et al., 1994). In the Western world, the population prevalence is estimated to be of the order of 0.5 % (Report of the CFS/ ME Working Group, 2002;Papanicolaou et al., 2004). Several factors have been proposed to account for the pathogenesis of CFS; however, the most widely believed theory is that the symptoms of this disease are mediated by immune mechanisms which, in turn, may be somehow induced by virus infection (Komaroff & Buchwald, 1998;Devanur & Kerr, 2006).Human parvovirus B19 (B19) is the aetiological agent of the rash illness erythema infectiosum, arthralgia and arthritis, transient aplastic crisis in patients with shortened red cell survival, fetal death and pure red cell aplasia in immunocompromised persons (Kerr & Modrow, 2006). B19 infection has also been shown to occur just prior to the onset of symptoms of CFS in several case reports and follow-up studies (Kerr et al., 2002). However, B19 seroprevalence in CFS patients is similar to that in the general population. The B19 genome consists of a linear, single-stranded DNA of~5.6 kb, encoding the two capsid proteins VP1 and VP2 from the right side and the non-structural protein (NS1) from the left side (Astell et al., 1997). The NS1 protein possesses DNA-nicking and helicase activities, is cytotoxic and trans-activates the human interleukin-6 gene (Moffatt et al., 1996). Immunity to B19 virus is mediated by both humoral and cellular means. Antibodies to NS1 occur in approximately 30 % of infected individuals and may indicate more persistent and severe courses of B19 infection (Searle et al., 1998).The present study was undertaken in view of the paucity of knowledge of the role of B19 infection in CFS patients and the human immune response to it. Findings of this study confirm that B19 seroprevalence in CFS patients is similar to that in the normal population. However, antibodies to the NS1 protein were elevated in frequency in CFS patients and were associat...

Role of Infection and Neurologic Dysfunction in Chronic Fatigue Syndrome

“…There were no differences in the frequency of IgG or IgM antibodies to structural proteins, but 42% of the CFS patients versus 7% of controls had IgG antibodies to the nonstructural protein, NS1, a marker associated with chronic and severe parvovirus infection. 182 …”

The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease

“…Detectable immune responses to the B19 NS1 protein have been shown to be associated with more severe courses of B19 infection,43 45 with chronic B19 arthritis44 and with chronic arthritis in the setting of chronic fatigue syndrome/myalgic encephalomyelitis 94…”

Article Commentary: Kynurenine Pathway Pathologies: Do Nicotinamide and Other Pathway Co-Factors have a Therapeutic Role in Reduction of Symptom Severity, Including Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM)

“…Genetic disorders of tryptophan and Vitamin B-12 status should be tested for, to exclude neurologic PA and other aberrations. Search for unexpected silent or chronic infections is required 2,48–50. In conclusion, the presence of nutritional3,31,68 and thyroid deficiencies and unsuspected infections offer a rational explanation as to the etiology of the patient’s signs and symptoms, such as ataxia, pain, paresthesias, and dysphorias 55…”