Detection of borna disease virus-reactive antibodies from patients with psychiatric disorders and from horses by electrochemiluminescence immunoassay

Abstract:

The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric disorders and healthy individuals has varied in several reports using several different serological assay methods. A reliable and specific method for anti-BDV antibodies needs to be developed to clarify the pathological significance of BDV infections in humans.

We developed a new electrochemiluminescence immunoassay (ECLIA) for the antibody to BDV that uses two recombinant proteins of BDV, p40 and p24 (full length). Using this ECLIA, we examined 3,476 serum samples from humans with various diseases and 917 sera from blood donors in Japan for the presence of anti-BDV antibodies.

By ECLIA, 26 (3.08%) of 845 schizophrenia patients and 9 (3.59%) of 251 patients with mood disorders were seropositive for BDV. Among 323 patients with other psychiatric diseases, 114 with neurological diseases, 75 with chronic fatigue syndrome, 85 human immunodeficiency virus-infected patients, 50 with autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosis and 17 with leprosy, there was no positive case except one case each with alcohol addiction, AIDS, and dementia.

Although 19 (1.36%) of 1,393 patients with various ocular diseases, 10 (1.09%) of 917 blood donors, and 3 (4.55%) of 66 multitransfused patients were seropositive for BDV-specific antigen, high levels of seroprevalence in schizophrenia patients and young patients (16 to 59 years old) with mood disorders were statistically significant.

The immunoreactivity of seropositive sera could be verified for specificity by blocking with soluble p40 and/or p24 recombinant protein. Anti-p24 antibody was more frequent than p40 antibody in most cases, and in some psychotic patients antibody profiles showed only p40 antibody. Although serum positive for both p40 and p24 antibodies was not found in this study, the p40 ECLIA count in schizophrenia patients was higher than that of blood donors.

Furthermore, we examined 90 sera from Japanese feral horses. Antibody profiles of control human samples are similar to that of naturally BDV-infected feral horses. We concluded that BDV infection was associated in some way with psychiatric disorders.

 

Source: Yamaguchi K, Sawada T, Naraki T, Igata-Yi R, Shiraki H, Horii Y, Ishii T, Ikeda K, Asou N, Okabe H, Mochizuki M, Takahashi K, Yamada S, Kubo K, Yashiki S, Waltrip RW 2nd, Carbone KM. Detection of borna disease virus-reactive antibodies from patients with psychiatric disorders and from horses by electrochemiluminescence immunoassay. Clin Diagn Lab Immunol. 1999 Sep;6(5):696-700. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC95757/ (Full article)

 

Autoimmune fatigue syndrome and fibromyalgia syndrome

Abstract:

We have encounted two patients with fibromyalgia (FM) initially diagnosed as having autoimmune fatigue syndrome (AIFS). To investigate the relationship between AIFS and FM, the distribution of the tender points in patients with AIFS was assessed according to the ACR criteria for FM.

It was revealed that AIFS patients had 5.6 tender points on averages. Patients with headaches, digestive problems, or difficulty going to school had more tender points than patients without. Patients with ANA titers < 1: 160 had more tender points than patients with ANA > or = 1: 160. Anti-Sa negative patients had more tender points than positive patients.

These results suggest a relationship between AIFS and FM in terms of the pathophysiologic mechanisms of the numerous tender points. In other words, ANA-positive FM patients could be one form of AIFS, as well as ANA-positive chronic fatigue syndrome patients. Thus, autoimmunity could explain the controversial disease entities of FM and/or CFS.

 

Source: Itoh Y, Igarashi T, Tatsuma N, Imai T, Yoshida J, Tsuchiya M, Murakami M, Fukunaga Y. Autoimmune fatigue syndrome and fibromyalgia syndrome. Nihon Ika Daigaku Zasshi. 1999 Aug;66(4):239-44. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/10466339

 

Prevalence of chronic fatigue syndrome in a community population in Japan

Abstract:

In order to know the prevalence of chronic fatigue syndrome (CFS) in a community population in Japan, we analyzed data from a population-based interview survey. Two cases out of 137 respondents experienced chronic fatigue during a period of nine months, suffered from 50% or more reduction of daily activity due to fatigue and had no other physical or psychiatric diagnosis. Both of the two cases fulfilled the 1994 Centers for Disease Control (CDC) criteria and the British criteria. The point and nine-month prevalence rates of CFS were both 1.5% (95% confidence intervals, 0.4-5.2%). None fulfilled the 1989 CDC criteria for CFS. The prevalence rate of CFS was higher than those in previous studies in the Western countries, suggesting a need for future research on cross-cultural differences in the definition, prevalence and symptomatology of CFS.

 

Source: Kawakami N, Iwata N, Fujihara S, Kitamura T. Prevalence of chronic fatigue syndrome in a community population in Japan. Tohoku J Exp Med. 1998 Sep;186(1):33-41. https://www.jstage.jst.go.jp/article/tjem/186/1/186_1_33/_article (Full article)

 

Dehydroepiandrosterone sulfate deficiency in chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS) is a condition of unknown etiology, characterized by a persistent debilitating fatigue, the muscle-related symptoms and the neuropsychiatric symptoms.

Recently, it has been reported that the patients with CFS might have impaired activation of the hypothalamic-pituitary-adrenal axis, and suggested that a part of the patho-genesis of CFS might be associated with abnormalities of the endocrine system.

Herein, we show that the majority of Japanese patients with CFS had a serum dehydroepiandrosterone sulfate (DHEA-S) deficiency. Serum DHEA-S is one of the most abundantly produced hormones which is secreted from the adrenal glands, and its physiological function is thought to be a precursor of sex steroids. DHEA-S has recently been shown to have physiological properties, such as neurosteroids, which are associated with such psychophysiological phenomena as memory, stress, anxiety, sleep and depression.

Therefore, the deficiency of DHEA-S might be related to the neuropsychiatric symptoms in patients with CFS.

 

Source: Kuratsune H, Yamaguti K, Sawada M, Kodate S, Machii T, Kanakura Y, Kitani T. Dehydroepiandrosterone sulfate deficiency in chronic fatigue syndrome. Int J Mol Med. 1998 Jan;1(1):143-6. http://www.ncbi.nlm.nih.gov/pubmed/9852212

 

Demonstration on Borna disease virus in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS), a recently named heterogeneous disorder, is an illness of unknown etiology. The association between CFS and several viral infection has been suggested. Here, we centered on the possible link between CFS and Borna disease virus (BDV) infection.

BDV is a neurotropic, nonsegmented negative-strand (NNS) RNA virus. Recent epidemiological data have suggested that BDV may be closely associated with depression and schizophrenia in humans.

In Japanese patients with CFS, the prevalence of BDV infection was 34% (30/89) and 12% (7/57) by immunoblotting and PCR analysis, respectively. Furthermore, anti-BDV antibodies and BDV RNA were detected in a family cluster with CFS. These results suggested that this virus contributes to or initiates CFS, although the single etiologic role of BDV is unlikely.

 

Source: Nakaya T, Kuratsune H, Kitani T, Ikuta K. Demonstration on Borna disease virus in patients with chronic fatigue syndrome. Nihon Rinsho. 1997 Nov;55(11):3064-71. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/9396313

 

Lack of association of Borna disease virus and human T-cell leukemia virus type 1 infections with psychiatric disorders among Japanese patients

Abstract:

Borna disease virus (BDV) infection has been suspected to be a possible etiological factor in human psychiatric disorders and recently in chronic fatigue syndrome. Evidence of the correlation of BDV infection with these disorders remained unclear. Kagoshima is known to be one of the major areas in which human T-cell leukemia virus type 1 (HTLV-1) is endemic; this is the first isolated human retrovirus that causes adult T-cell leukemia with neurological symptoms. The present study aimed to clarify whether BDV and HTLV-1 infections are associated with psychiatric disorders among Japanese patients.

Subjects were 346 patients with psychiatric disorders (schizophrenia, 179; mood disorder, 123; and others, 44) and 70 healthy controls. Anti-BDV antibodies from plasma samples were screened by the indirect immunofluorescence (IF) method using BDV-infected MDCK cells. Results revealed that only three samples were found to be weakly positive for BDV in the IF assay and seronegative by Western blot (immunoblot) assay.

Furthermore, BDV-p24 related RNA in peripheral blood mononuclear cells from 106 of 346 psychiatric patients and 12 or 70 healthy controls by p24-reverse transcription PCR was examined. Two mood disorder patients were positive for BDV-p24 RNA but seronegative. To detect anti-HTLV-1 antibodies the plasma samples were screened by the particle agglutination method and no significant difference in seropositivity for anti-HTLV-1 antibody was found between the patients and healthy controls.

These results also suggested that there is a lack of association between BDV and HTLV-1 infections with psychiatric disorders among Japanese patients.

 

Source: Kubo K, Fujiyoshi T, Yokoyama MM, Kamei K, Richt JA, Kitze B, Herzog S, Takigawa M, Sonoda S. Lack of association of Borna disease virus and human T-cell leukemia virus type 1 infections with psychiatric disorders among Japanese patients. Clin Diagn Lab Immunol. 1997 Mar;4(2):189-94. http://www.ncbi.nlm.nih.gov/pubmed/9067654

 

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment

Abstract:

This study is a counterpart of the pilot study on the clinical management of chronic fatigue syndrome (CFS) by the combined use of the old (annex-free) and the new (dehydro-epiandrosterone- annexed) vitamin C infusion treatments with and without oral intake of erythromycin and chloramphenicol. We were motivated to start this clinical study by 2 reasons:

i) we have made a success in the clinical management of autoimmune disease and allergy by use of the old megadose vitamin C infusion treatment, and we therefore took up CFS as a good candidate for vitamin C infusion treatment;

ii) In 1995, we received a total of 313 chronic pneumonia patients whose clinical course showed a good fitness to the criteria of CFS.

We assessed the nature of the disease by investigating the clinicoepidemiological aspect of our patients on the one hand and the response of the disease to both the old and new vitamin C infusion treatments with and without the use of 2 antibiotics on the other hand. Results are summarized as follows:

a) the analysis of the medical records of our outpatients revealed that chronic type pneumonia epidemic in Nagoya Japan, with its onset of January 1995, showed no sign of its extinction by the end of May 1996. The patient population contained no patients under 15 years of age, and showed a distinct female predominance in the patient number (207 females versus 106 males). In 1995, we also experienced a simple cold epidemic with its onset of January 1995 (162 males and 224 females). The majority of simple cold patients were under 25 years of age in both sexes.

b) A chronic type pneumonia patient was distinguished from a simple cold patient in 2 respects: firstly the former required prolonged medical care (over 1 month) resulting in an incomplete cure and return to medical care upon the recurrence of disease, whereas the latter required short-term medical care (mostly within 1 week) ending up with complete cure. Secondly, the former required the long term use of 2 antibiotics (erythromycin and chloramphenicol) together with regular practice of the old and new vitamin C infusion treatments for disease control, whereas the latter recovered from the disease after the short time use of a set of conventional cold remedies.

c) The clinical manifestations of our chronic pneumonia patients showed good fitness to the criteria of CFS.

d) CFS was distinguished from autoimmune disease-allergy complex by the method of clinical control: the former required the long-term use of 2 antibiotics together with regular practice of the old and new vitamin C infusion treatments, whereas the latter was controllable by the single use of the old vitamin C infusion treatment.

e) The combined use of the old and new vitamin C infusion treatments rather than the single use of the old vitamin C infusion treatment was more effective for the control of CFS-a finding which suggests that deficient activities of both endogenous glucocorticoid and endogenous androgen in a CFS patient are somehow related to the genesis and further development of CFS.

f) Evidence was available to indicate that the sole use of the new vitamin C infusion treatment may induce a state of gonadal steroid excess together with various other problems in the recipient. The maintenance of a good balance between the old vitamin C infusion set (glucocorticoid-inducer) and the new vitamin C infusion set (inducer of both glucocorticoid and gonadal steroids) in their use was of prime importance for the successful control of CFS.

g) The historical significance of CFS epidemic in 1995, and in Nagoya-Japan, is discussed in the light of the new infection concept.

 

Source: Kodama M, Kodama T, Murakami M. The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment. In Vivo. 1996 Nov-Dec;10(6):585-96. http://www.ncbi.nlm.nih.gov/pubmed/8986468

 

Descriptive epidemiology of chronic fatigue syndrome based on a nationwide survey in Japan

Abstract:

In order to clarify the epidemiological features of chronic fatigue syndrome (CFS), a nationwide survey was conducted using the Japanese version of the CDC Criteria prepared by the CFS Research Group of Japan. All clinical departments of internal medicine, pediatrics, psychiatry and neurology at university hospitals and at ordinary hospitals with 200 or more beds were surveyed.

Major results were as follows: (1) Period prevalence adjusted for response rate was 0.85 (0.63 for males and 1.02 for females) per 100,000 population during the year 1992; (2) Based on the first and final dates of hospital visits, the prevalences on January 1 of 1992 and 1993 were 0.40 and 0.60 per 100,000 population, respectively, suggesting an increasing trend; (3) Reported new cases during 1992 were 301, and the response adjusted-incidence was estimated to be 0.46 per 100,000 person-years; (4) The proportion of post-infectious CFS cases was 14.8% for both sexes, and tended to be slightly higher among females than males, but was not related to age. Three clusterings of two cases were reported.

 

Source: Minowa M, Jiamo M. Descriptive epidemiology of chronic fatigue syndrome based on a nationwide survey in Japan. J Epidemiol. 1996 Jun;6(2):75-80. https://www.jstage.jst.go.jp/article/jea1991/6/2/6_2_75/_pdf (Full article)

 

Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with chronic fatigue syndrome

Abstract:

CFS, a recently named heterogeneous disorder, is an illness of unknown etiology. The association of CFS with viral infections has been suggested. A common association between CFS and several viruses examined has not been confirmed.

Here, we centered on the possible link between CFS and BDV infection. By nested RT-PCR followed by hybridization, BDV RNA was demonstrated as a clear signal in PBMCs in 3 out of 25 CFS patients. The amplified cDNA fragments were cloned and sequenced. A total of 16 clones were studied. Intra-patients divergencies of the p24 were 2-9%, 3-20%, and 3-11% in the deduced amino acids. Inter-patient divergencies among the 16 clones were 3-24%. Antibodies to recombinant BDV p24 protein were detected in 6 CFS patients including one carrying BDV RNA.

Overall, these gave the prevalence of 32% (8/25) in Japanese CFS patients, suggesting that Japanese CFS is highly associated with active infection of BDV, or a related agent.

 

Source: Nakaya T, Takahashi H, Nakamura Y, Asahi S, Tobiume M, Kuratsune H, Kitani T, Yamanishi K, Ikuta K. Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with chronic fatigue syndrome. FEBS Lett. 1996 Jan 8;378(2):145-9. http://onlinelibrary.wiley.com/doi/10.1016/0014-5793(95)01439-X/epdf (Full article)

 

Possible correlation between Borna disease virus infection and Japanese patients with chronic fatigue syndrome

Abstract:

Borna disease virus (BDV) is a neurotropic, as yet unclassified, non-segmented, negative-sense, single-strand RNA virus. Natural infection with this virus has been reported to occur in horses and sheep. In addition, antibodies to BDV in plasma or BDV RNA in peripheral blood mononuclear cells (PBMCs) were also found in patients with neuropsychiatric diseases. We describe here the possible link between the patients with chronic fatigue syndrome (CFS) and infection with BDV.

 

Source: Kitani T, Kuratsune H, Fuke I, Nakamura Y, Nakaya T, Asahi S, Tobiume M, Yamaguti K, Machii T, Inagi R, Yamanishi K, Ikuta K. Possible correlation between Borna disease virus infection and Japanese patients with chronic fatigue syndrome. Microbiol Immunol. 1996;40(6):459-62. http://www.ncbi.nlm.nih.gov/pubmed/8839433