R Wank

Université de Mons, Mons, Walloon, Belgium

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Publications (86)489.38 Total impact

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    ABSTRACT: TNFα is a very potent and pleiotropic pro-inflammatory cytokine, essential to the immune system for eradicating cancer and microorganisms, and to the nervous system, for brain development and ongoing function. Yet, excess and/or chronic TNFα secretion causes massive tissue damage in autoimmune, inflammatory and neurological diseases and injuries. Therefore, many patients with autoimmune/inflammatory diseases receive anti-TNFα medications. TNFα is secreted primarily by CD4(+) T cells, macrophages, monocytes, neutrophils and NK cells, mainly after immune stimulation. Yet, the cause for the pathologically high and chronic TNFα secretion is unknown. Can blocking of a particular ion channel in T cells induce by itself TNFα secretion? Such phenomenon was never revealed or even hypothesized. In this interdisciplinary study we discovered that: (1) normal human T cells express Kv1.1 voltage-gated potassium channel mRNA, and the Kv1.1 membrane-anchored protein channel; (2) Kv1.1 is expressed in most CD4(+)CD3(+) helper T cells (mean CD4(+)CD3(+)Kv1.1(+) T cells of 7 healthy subjects: 53.09 ± 22.17 %), but not in CD8(+)CD3(+) cytotoxic T cells (mean CD8(+)CD3(+)Kv1.1(+) T cells: 4.12 ± 3.04 %); (3) electrophysiological whole-cell recordings in normal human T cells revealed Kv currents; (4) Dendrotoxin-K (DTX-K), a highly selective Kv1.1 blocker derived from snake toxin, increases the rate of rise and decay of Kv currents in both resting and activated T cells, without affecting the peak current; (5) DTX-K by itself induces robust TNFα production and secretion by normal human T cells, without elevating IFNγ, IL-4 and IL-10; (6) intact Ca(2+) channels are required for DTX-induced TNFα secretion; (7) selective anti-Kv1.1 antibodies also induce by themselves TNFα secretion; (8) DTX-K activates NFκB in normal human T cells via the unique non-canonical-pathway; (9) injection of Kv1.1-blocked human T cells to SCID mice, causes recruitment of resident mouse cells into the liver, alike reported after TNFα injection into the brain. Based on our discoveries we speculate that abnormally blocked Kv1.1 in T cells (and other immune cells?), due to either anti-Kv1.1 autoimmune antibodies, or Kv1.1-blocking toxins alike DTX-K, or Kv1.1-blocking genetic mutations, may be responsible for the chronic/excessive TNFα in autoimmune/inflammatory diseases. Independently, we also hypothesize that selective block of Kv1.1 in CD4(+) T cells of patients with cancer or chronic infectious diseases could be therapeutic, since it may: a. augment beneficial secretion and delivery of TNFα to the disease-affected sites; b. induce recruitment and extravasation of curative immune cells and factors; c. improve accessibility of drugs to the brain and few peripheral organs thanks to TNFα-induced increased permeability of organ's barriers.
    No preview · Article · Nov 2015 · Journal of Neural Transmission
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    ABSTRACT: In previous studies we found that several Neurotransmitters and Neuropeptides among them: Glutamate, Dopamine, Gonadotropin-releasing-hormone (GnRH) I and II, Somatostatin, CGRP and Neuropeptide Y, can each by itself, at low physiological concentration (~10 nM) bind its receptors in human T cells and trigger several key T cell functions. These findings showed that the nervous system, via Neurotransmitters and Neuropeptides, can 'talk' directly to the immune system, and stimulate what we coined 'Nerve-Driven Immunity': immune responses dictated by the nervous system. In various human cancers, the immune system of the patients, and their T cells in particular, are not functioning well enough against the cancer due to several reasons, among them the suppressive effects on the immune system induced by: (1) the cancer itself, (2) the chemotherapy and radiotherapy, (3) the ongoing/chronic stress, anxiety, depression and pain felt by the cancer patients. In Head and Neck Cancer (HNC), 5-year survival rate remains below 50 %, primarily because of local recurrences or second primary tumors. Two-thirds of HNC patients are diagnosed at advanced clinical stage and have significantly poorer prognosis. Most HNC patients have multiple severe immunological defects especially in their T cells. A major defect in T cells of patients with HNC or other types of cancer is low CD3zeta expression that correlates with poor prognosis, decreased proliferation, apoptotic profile, abnormal cytokine secretion and poor abilities of destructing cancer cells. T cells of cancer patients are often also unable to migrate properly towards the tumor. In this study we asked if Glutamate, Dopamine or GnRH-II can augment the spontaneous migration, chemotactic migration and towards autologous HNC migration, and also increase CD3zeta and CD3epsilon expression, of peripheral T cells purified from the blood of five HNC patients. These HNC patients had either primary tumor or recurrence, and have been already treated by surgery and/or radiotherapy and/or chemotherapy without satisfactory outcomes. We found that Glutamate, Dopamine and GnRH-II, each by itself, at 10 nM, and during 30 min incubation only with the peripheral T cells of the HNC patients increased substantially their: (1) spontaneous migration (up to 4.4 fold increase), (2) chemotactic migration towards the key chemokine SDF-1 (up to 2.3 fold increase), (3) migration towards the autologous HNC tumor removed surgically ~48 h earlier in a pre-planned operation (up to 3.5 fold increase). Each of the Neurotransmitters even 'allowed' the T cells of one HNC patient to overcome completely the suppressive anti-migration effect of his autologous tumor, (4) cell surface CD3zeta expression (up to 4.3 fold increase), (5) cell surface CD3epsilon expression (up to 1.9 fold increase). If the absolutely essential larger scale subsequent studies would validate our present findings, Glutamate, Dopamine and GnRH-II could be used for a completely novel indication: adoptive T cell immunotherapy for some patients with HNC and maybe also other types of cancer. We coin here a novel term-'Neuroimmunotherapy' for this new form of T cell immunotherapy, based on the direct activation of the patient's own T cells by Neurotransmitters. Such 'Neuroimmunotherapy' could be reduced to practice by rather simple, painless and repeated/periodical removal of peripheral T cells from the cancer patients, activating them ex vivo for 30 min by either Glutamate, Dopamine or GnRH-II, and infusing them back to the patients by intravenous and/or intratumoral injection. The 'rejuvenated' Neurotransmitter-treated T cells are expected to have significantly improved abilities to reach and eradicate the cancer, and also combat infectious organisms that cancer patients often suffer from. Since the T cells are autologous, since the Neurotransmitters are physiological molecules, and since the ex vivo 'parking period' is very short, such Neuroimmunotherapy is expected to be very safe.
    No preview · Article · Jul 2014 · Journal of Neural Transmission
  • Barbara Lösch · Rudolf Wank
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    ABSTRACT: Non-hereditary angioedema is a common disease with a prevalence between 5% and 19% and approximately half of the patients experience a swelling of the tongue. We report a case of a 49-year-old Caucasian man with a gross life-threatening angioedema of the tongue, whose attacks occurred every 4 weeks. The most frequent causes of angioedema were excluded. We detected DNA and RNA from Bartonella henselae in the blood and saliva of the patient and in the saliva of the patient's hunting dog. Treatment with azithromycin plus minocycline cleared the blood and saliva of RNA and DNA of Bartonella species, and the patient has been free from angioedema for 1 year. None of the therapy modalities used to treat the hereditary form or ACE or allergy-induced angioedema affect the detrimental course caused by Bartonella species. We therefore suggest that a molecular Bartonella test be included in the analysis of angioedema.
    No preview · Article · Mar 2014 · Case Reports
  • Rudolf Wank · Xin Song · Songhai Gu · Barbara Laumbacher
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    ABSTRACT: A growing body of evidence shows that immune cells are pivotal in the fight against cancer. First, association studies have identified immune-protective immune response genes against cancer. Second, the presence of immune cells in the respective malignant tumor correlated with a better prognosis for the patients. Third, adoptive cell therapy (ACT) showed, in recent reports, an efficient reduction or even cure for malignant tumors. The focus of this review is a novel in vitro ACT technique, using the patient's cascade-primed immune cells. The cascade-priming procedure stimulates APCs from the peripheral blood. Stimulated APCs digest and present tumor material better and differentiate naive cytotoxic T-lymphocyte effector cells against the patient's cancer. The principle and the impressive results of the cascade-primed immune cell treatment in patient case series is compared with the ACT concepts of lymphokine-activated killer, macrophage-activated killer, macrophage-activated killer-dendritic cell, cytokine-induced killer and tumor-infiltrating lymphocyte methods.
    No preview · Article · Mar 2014 · Immunotherapy
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    Barbara Laumbacher · Songhai Gu · Rudolf Wank
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    ABSTRACT: Despite newer treatment modalities, few patients with non-small cell lung cancer in stages IIIB and IV survive the median of one year. We present four patients with non-small cell lung cancer treated with an adjuvant therapy with cascade primed immune cells. The in vitro stimulated expression of cancer information on the patients' monocytes matures and activates T lymphocytes to destroy cancer cells. The cascade primed immune cell therapy significantly improved the quality of life and the lifespan of all four patients; thus far, three patients survived 40, 55 and 120 months, respectively; and one patient died 39 months after diagnosis. Patient 1, stage IV (T4N2M1): The adenocarcinoma of the 67-year-old German Caucasian man infiltrated into the mediastinal lymph nodes and iliosacral bones. Chemotherapy modalities were started immediately after diagnosis of cancer, and cascade primed immune cell therapy one year later. The patient survived 39 months.Patient 2, stage IV (T3N3M1a): The 62-year-old German Caucasian woman presented with adenocarcinoma of the lower lobe with infiltrated lymph nodes of the mediastinum and malignant pleural effusion. Chemotherapy, radiation and the cascade primed immune cell therapy were administered together. The patient is still alive after 40 months.Patient 3, stage IIIB (T4N1-2M0): The 75-year-old German Caucasian woman presented with an undifferentiated tumor and a separate tumor nodule in the ipsilateral lobe. The patient received only cascade primed immune cell therapy after tumor resection and has survived for the last 55 months.Patient 4, pancoast tumor (IIIB, T3N3M0): The 77-year-old German Caucasian man presented with an undifferentiated tumor that infiltrated the lymph nodes, the clavicle, one rib and the plexus brachialis. In addition to chemotherapy and radiation, cascade primed immune cells were administered every weekday for one year. After four months, no living tumor cell was detected in the resected lung, the lymph nodes or the bone material. The patient is still alive after 120 months. The novel adoptive cell therapy with cascade primed immune cells significantly increased the survival rate and maintained the quality of life for four patients with non-small cell lung cancer in stages IIIB and IV. Our findings indicate that tumor resection, chemotherapy and radiation appear to support the cascade primed immune cell therapy.
    Preview · Article · Dec 2013 · Journal of Medical Case Reports
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    ABSTRACT: Chlamydia has attracted increased attention as a possible cause of atheromatous plaques, cerebrovascular diseases, multiple sclerosis, Alzheimer's disease and schizophrenia. The Chlamydia species are obligate intracellular parasites. The unique biphasic life cycle of Chlamydia permits the parasite to persist in cells for years. Acute Chlamydia infections can be recognized serologically in the peripheral blood through observation of rising antibody titers or molecularly using various PCR methods. However, the identification of chronic Chlamydia infection is hampered by many hurdles. This has initiated controversial discussions about the true involvement of Chlamydia, particularly in the CNS. The aspects of the discussion will be inspected as well as the vulnerability of the neuronal MHC to immune reactions.
    No preview · Article · Jan 2013 · Future Neurology
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    ABSTRACT: Neuronal MHC/HLA regulates the synapses of the central nervous system (CNS). The expression of MHC/HLA is, in turn, regulated by immune cytokines. We were therefore interested in the regulation of schizophrenia-associated HLA antigens, specifically their regulation of expression by interferons. We had previously observed a moderately increased frequency of HLA-A10 expression in schizophrenic patients. While searching for the "true" disease gene near the HLA-A gene, we discovered that homozygosity of the HLA-J M80469 pseudogene allele, in combination with HLA-A10 or HLA-A9, was associated with a high risk of schizophrenia (HLA-A10 relative risk=29.33, p=0.00019, patients N=77, controls N=214). The allele HLA-J M80468, which codes for interferon-inducible mRNA, conferred protection on carriers of HLA-A9 and HLA-A10 (HLA-A10 relative risk=0.022, p=0.00017). Functional analysis revealed that interferon γ (IFNγ) downregulated the expression of HLA-A9 and HLA-A10 in monocytes from HLA-J M80469 homozygous patients but not from carriers of the HLA-J M80468 allele. This is the first demonstration of an inverse effect of IFNγ on HLA expression that is associated with non-coding gene variants and schizophrenia. Our findings suggest that the interferons secreted during acute and chronic infections may interfere in synaptic regulation via neuronal HLA and that this disturbance in synaptic regulation may induce the symptoms of mental illness.
    No preview · Article · Sep 2012 · Immunobiology
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    B Laumbacher · S Gu · R Wank
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    ABSTRACT: It has not been considered so far that antigen-presenting cells (APC) may phagocytose immunogenic material from autologous cancer cells. Assuming the presence of cancer-immunogenic material in APC, we developed a novel autologous priming method that does not require tumour cells or identified peptides. Cancer-immunogenic information came from CD14+ monocytes. When stimulated with CD3-activated T cells, monocytes primed CD3+ CD4+ and CD3+ CD8+ resting/naïve T cells to become powerful effector cells within 24 h. During priming, depletion of CD14+ monocytes but not CD1a+ CD83+ dendritic cells prevented T cell priming. During cancer cell destruction, dendritic cells, but not monocytes, enhanced cancer cell lysis. The cascade-primed (CAPRI) immune cell quartet comprising monocytes, dendritic cells, CD4+ T and CD8+ T cells induced a significant decrease in the number of suppressive CD25(high) FoxP3+ CD4+ T cells. CAPRI cells induced a marked upregulation of MHC class I and class II expression in cancer cells, which is crucial for autoimmune-like lysis. We show in vivo evidence of the CAPRI cell concept in nude mice. In humans, we present circumstantial clinical evidence showing the efficacy of CAPRI cells in an adjuvant treatment attempt for breast cancer patients with metastasis (N = 42). Compared to patients at the Munich Tumor Center (no CAPRI treatment N = 428), almost double the expected number of patients survived 5 years (P =1.36 × 10⁻¹⁴). The CAPRI method is a safe procedure without negative side effects. High numbers of cancer-specific CAPRI cells can be obtained within a week against different cancer types for efficient adoptive cell therapy.
    Preview · Article · Mar 2012 · Scandinavian Journal of Immunology
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    ABSTRACT: An 82-year-old Caucasian woman had remained in a persistent vegetative state after a coma of seven months duration, which occurred after a stroke with hemiplegia, nine years previously. The persistent vegetative state could be reversed in part by weekly injections with activated immune cells. After therapy, our patient responded to commands in addition to regaining spontaneous movements of both arms and the ability to swallow. This is the first report on the treatment with activated immune cells of a patient in a persistent vegetative state after a coma. An 82-year-old Caucasian woman presented with a persistent vegetative state subsequent to a coma. She retained respiratory and autonomic functions. As contact was not possible, physiotherapy was passive. Her skin was yellowish, and our patient did not move by herself. Vomiting repeatedly resulted from tube feeding. After a once-weekly treatment with activated immune cells sampled from our patient's blood and activated in vitro, several of her functions gradually returned. Our patient opened her eyes in the requested direction and turned her head toward people entering the room. She 'supported' nursing efforts, as the nurse noted a loss of spastic motions. The strength in both her arms returned, and she spontaneously moved her arm on the side experiencing hemiplegia. After three months, our patient could stick out her tongue upon demand. Finally, the swallow reflexes of our patient started to return. However, tube feeding was continued, and our patient died after aspiration of vomit following a feeding. The success of treatment with autologous activated immune cells in this patient may have resulted from the production of neuroactive substances, such as neurotrophin-3 and brain-derived neurotrophic factor, by activated immune cells. The deterioration of our patient could be reversed, as demonstrated by the restoration of motor strength in her hemiplegic side. In addition, our patient was able to induce motor responses upon request. It seems reasonable to conclude that activated immune cells may improve the chronic vegetative state in some patients.
    Preview · Article · Jan 2012 · Journal of Medical Case Reports
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    ABSTRACT: Destruction of cancer cells by cytotoxic T lymphocytes depends on immunogenic tumor peptides generated by proteasomes and presented by human leukocyte antigen (HLA) molecules. Functional differences arising from alleles of immunoproteasome subunits have not been recognized so far. We analyzed the genetic polymorphism of the immunoproteasome subunits LMP2 and LMP7 and of the transporters associated with antigen processing (TAP1 and TAP2) in two independently collected panels of colorectal carcinoma patients (N(1) = 112, N(2) = 62; controls, N = 165). High risk of colon cancer was associated with the LMP7-K/Q genotype (OR = 8.10, P = 1.10 × 10(-11)) and low risk with the LMP7-Q/Q genotype (OR = 0.10, P = 5.97 × 10(-13)). The basis for these distinct associations of LMP7 genotypes was functionally assessed by IFN-γ stimulation of colon carcinoma cell lines (N = 10), followed by analyses of mRNA expression of HLA class I, TAP1, TAP2, and LMP7, with real-time PCR. Whereas induction of HLA-B, TAP1, and TAP2 was comparable in all cell lines, transcript amounts of LMP7-Q increased 10-fold, but of LMP7-K only 3.8-fold. This correlated with a reduced transcript stability of LMP7-K (t(1/2) ≈ 7 minutes) compared with LMP7-Q (t(1/2) ≈ 33 minutes). In addition, LMP7-Q/Q colon carcinoma cells increased (the peptide based) HLA class I surface expression significantly after IFN-γ stimulation, whereas LMP7-Q/K and LMP7-K/K carcinoma cells showed minimal (<20%) changes. These results suggest that the presence of LMP7-K can reduce the formation of immunoproteasomes and thus peptide processing, followed by reduced peptide-HLA presentation, a crucial factor in the immune response against cancer.
    Full-text · Article · Dec 2011 · Cancer Research
  • Barbara Fellerhoff · Rudolf Wank
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    ABSTRACT: Infection can initiate symptoms of mental illness. It has been shown previously that Chlamydophila DNA is present six times more often in the blood of patients with schizophrenia than in the blood of control individuals. Monocytes, the main targets of Chlamydiaceae infection, are microglia precursors. We identified Chlamydiaceae infection using blinded brain DNA samples derived from the frontal cortex. Using PCR and sequence analysis, we found Chlamydophila DNA to be four times greater in patients with schizophrenia than in controls (schizophrenia: N=34, microbial DNA frequency 23.5%; controls: N=35, microbial DNA frequency 5.7%; P=0.045, OR=5.08). Persistent Chlamydophila-infected microglia or neuronal cells may impair neuronal circuits and thus be a mechanism for causing psychiatric illness in these patients.
    No preview · Article · Jul 2011 · Schizophrenia Research
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    ABSTRACT: Collecting duct carcinoma (CDC) or Bellini duct carcinoma of the kidney is a rare, but highly aggressive renal epithelial malignancy, with an extremely poor prognosis. Modified cytokine-induced killer (mCIK) cells were injected into the pleural cavity to treat pleural metastasis of CDC. The patient, a 33-year-old male, was admitted to hospital for further treatment for severe pleural metastasis of CDC. We cured the pleural metastasis through intrapleural infusion with mCIK cells. After receiving this innovative treatment, the patient exhibited a positive response: the cough, dyspnea, chest distress and thoracalgia were evidently relieved, while the pleural fluid became clear after exhibiting haematodes and its level decreased significantly. The patient achieved partial success. This novel immunotherapy method is a promising treatment for patients with refractory pleural metastasis.
    Preview · Article · Nov 2010 · Oncology letters
  • Barbara Fellerhoff · Rudolf Wank

    No preview · Article · Jul 2009 · Brain Behavior and Immunity
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    ABSTRACT: Several microbes have been suspected as pathogenetic factors in schizophrenia. We have previously observed increased frequencies of chlamydial infections and of human lymphocyte antigen (HLA)-A10 in independent studies of schizophrenia. Our aim here was to analyze frequencies of three types of Chlamydiaceae in schizophrenic patients (n=72), random controls (n=225) and hospital-patient controls (n=36), together with HLA-A genotypes. Patients were diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders-IV. Blood samples were collected at the beginning of hospitalization and analyzed with Chlamydiaceae species-specific polymerase chain reaction (PCR). Control panels consisted of randomly selected volunteers and hospitalized, non-schizophrenic patients. We found chlamydial infection in 40.3% of the schizophrenic patients compared to 6.7% in the controls. The association of schizophrenia with Chlamydiaceae infections was highly significant (P=1.39 x 10(-10), odds ratio (OR)=9.43), especially with Chlamydophila psittaci (P=2.81 x 10(-7), OR=24.39). Schizophrenic carriers of the HLA-A10 genotype were clearly most often infected with Chlamydophila, especially C. psittaci (P=8.03 x 10(-5), OR=50.00). Chlamydophila infections represent the highest risk factor yet found to be associated with schizophrenia. This risk is even further enhanced in carriers of the HLA-A10 genotype.
    Preview · Article · Apr 2007 · Molecular Psychiatry
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    ABSTRACT: We ask consulting patients regularly whether they keep pets in order to identify zoonotic factors. It became apparent that patients with breast carcinoma (N=69) owned significantly more often dogs but not cats compared to age matched female controls. We compared the frequencies of dog and pet ownership with data from public available statistics on women (N=1320) of the same age group in Bavaria. The most striking result was that more than twice the number of patients kept dogs permanently in the last 10 years and at the time of interrogation as compared to control individuals at the time of interrogation (p=0.0000003, relative risk 3.5). Further internet search on the morbidity of breast carcinoma showed in dogs a protracted course of disease and metastases into lung, liver and bones, resembling the course of disease in human breast cancer. In contrast with this, breast cancer presented in cats a dramatically short course and the main but unusual location of metastasis presents in the hind legs. A recent publication in Norway reported on a high frequency (53.3%) of breast carcinomas in 14,401 investigated dogs. Which transmissible factor or factors come into question? Variants of the mouse mammary tumor virus (MMTV) can productively replicate in human cells and in different animals, including dogs. Many investigators, but not all, could identify MMTV-like sequences in sporadic human breast cancer. MMTV or MMTV-like sequences have not been investigated in canine breast carcinomas until now. It is also conceivable that other microbes from the dog, for example bacteria, could participate in the first steps of carcinogenesis in human. It was recently shown that bartonella species promote vascularization and prevent apoptosis of infected cells with the same methods as helicobacter pylori. Our considerations require further research. Epidemiologic cohort studies and identification of potential carcinogenic microbial factors will prove or disprove our hypothesis that risk factors from dogs could contribute to the carcinogenesis of human breast cancer.
    Full-text · Article · Feb 2006 · Medical Hypotheses
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    ABSTRACT: Many microbial factors have been implicated as pathogenic factors in mental disorders. Occurrence of such microbial factors also in the mentally unaffected population raised skepticism against such findings, although each microbial factor may cause mental problems only in some individuals, depending on the individual's immunogenetic disposition. Skepticism against the role of infection in schizophrenia was also fostered by the low impact of antiinfections treatment on the course of disease progression in schizophrenia. We discovered previously that neurotrophins like neurotrophin3 (NT-3) and brain-derived neurotrophic factor (BDNF), involved in processes of neuroplasticity, are also secreted by immune cells, but only by subpopulations of immune cells. Therefore, infection of the immune cell subpopulation, specialized in secreting BDNF, or of another subpopulation, specialized in secreting NT-3, could distort communication of immune cells with the central nervous system (CNS). Chlamydiaceae could cause disbalancement of immune cell sub-populations and, in some individuals with a vulnerable disposition, symptoms of mental illness. Based on previous observations of persisting IgA titers in some patients with mental illness we hypothesize that the intracellular parasites Chlamydiaceae are main pathogenic factors in schizophrenia. We hypothesize furthermore that antiinfectious treatment has to be accompanied by adoptive immunotherapy because antibiotics alone will not restore the balance of immune subpopulations. Our hypothesis is supported by examination of patients with schizophrenia and other mental disorders. Using nested PCR we found a significant prevalence of the intracellular parasites Chlamydophila psittaci, C. pneumoniae and Chlamydia trachomatis (9/18, 50%), as compared to controls (8/115, 6.97%) (chi(2)=25.86, Fisher's exact p two-tailed=5x10(-5)). Treatment with in vitro-activated immune cells together with antibiotic modalities showed sustained mental improvements in patients that did not depend on treatment with antipsychotic drugs. Future controlled studies including sham treatment of patients have to be carried out to prove our hypotheses.
    No preview · Article · Feb 2005 · Medical Hypotheses
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    Full-text · Article · Apr 2003 · Journal of Medical Genetics
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    Full-text · Article · Nov 2002 · Journal of Medical Genetics
  • Rudolf Wank
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    ABSTRACT: Many different microbial factors seem to contribute to the pathogenesis of schizophrenic and other psychiatric disorders. Activation of all T lymphocytes reactivates those downregulated by low-grade chronic infections and restores equilibrium in immune cell subpopulations. Different immune cell subpopulations express different neurotrophin receptors and produce different cytokines, particularly brain-derived neurotrophin (BDNF) and neurotrophin 3 (NT3) [M. Besser, R. Wank, J. Immunol. 162 (1998) 6303-6306] that appear to play a key role in schizophrenic and bipolar disorders [E. Jonsson, S. Brene, X.R. Zhang, et al., Acta Psychiatr. Scand. 95 (1997) 414-419; R.S. Duman, Arch. Gen. Psychiatry 54 (1997) 597-606; J.A. Siuciak, D.R. Lewis, S.J. Wiegand, R.M. Lindsay, Pharmacol. Biochem. Be 56 (1997) 131-137]. The hypothesis that adoptive immunotherapy is effective in psychiatric disorders will be supported by three case reports, in a patient with bipolar disorder, a patient with schizophrenia, and a patient with autism.
    No preview · Article · Sep 2002 · Medical Hypotheses
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    ABSTRACT: The viral CC chemokine macrophage inhibitory protein-II (vMIP-II) encoded by human herpes virus 8 (HHV-8) binds to multiple chemokine receptors, however, its ability to control the initial recruitment of specific leukocyte subtypes from the peripheral circulation has not been fully clarified. Here we show that vMIP-II blocks the firm arrest and transmigration of monocytes or Th1-like T lymphocytes triggered by RANTES immobilized on activated human microvascular endothelium (HMVEC) under flow conditions. The internalization of the receptors CCR1 and CCR5 that mediate arrest and transmigration of these cells in response to RANTES was prevented by vMIP-II, supporting its role as an antagonist of CCR1 and CCR5. In contrast, vMIP-II triggered the firm arrest of eosinophils and Th2-like T cells by engaging CCR3, as confirmed by its down-regulation. Immunohistochemical analysis of HHV-8-associated Kaposi's sarcoma lesions marked by vMIP-II expression and mononuclear cell infiltration revealed a predominance of Th2-type CCR3+ lymphocytes over Th1-type CXCR3+/CCR5+ leukocytes, indicating that as a CCR3 agonist vMIP-II can drive a Th2-type immune responsein vivo. Thus, our data provide evidence for a immunomodulatory role of vMIP-II in directing inflammatory cell recruitment away from a Th1-type towards a Th2-type response and thereby facilitating evasion from cytotoxic reactions.
    No preview · Article · Aug 2001 · European Journal of Immunology

Publication Stats

2k Citations
489.38 Total Impact Points


  • 2014
    • Université de Mons
      • Faculty of Medicine and Pharmacy
      Mons, Walloon, Belgium
  • 1998-2007
    • Ludwig-Maximilian-University of Munich
      • • Institute for Immunology
      • • Department of Psychiatry
      München, Bavaria, Germany
    • Institut für Immunologie und Genetik
      Kaiserlautern, Rheinland-Pfalz, Germany
  • 1981-2002
    • University Hospital München
      München, Bavaria, Germany
  • 1992
    • Technische Universität München
      München, Bavaria, Germany
  • 1980
    • National Institutes of Health
      Maryland, United States
    • Leiden University
      Leyden, South Holland, Netherlands
  • 1978-1979
    • Memorial Sloan-Kettering Cancer Center
      New York, New York, United States