Pathogenesis of neuroimmunologic diseases

Animal models of autoimmune diseases have greatly improved our current understanding of the pathogenesis of human autoimmunity and have provided the potential for therapies based on manipulation of the immune system. In our laboratory, we have investigated the immunopathogenesis of autoimmune diseases of the nervous system and muscle. We have developed immune-based approaches for the suppression of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), and experimental autoimmune neuritis (EAN), a model for the Guillain-Barré syndrome (GBS). These approaches included induction of peripheral tolerance, immunotoxin targeting of activated T cells, and cytokine manipulations. In addition, we identified the antigen and characterized immunopathologically an autoimmune inflammatory disease of skeletal muscle, experimental autoimmune myositis (EAM), a model for the human inflammatory muscle disease polymyositis.     

Chemokines and peripheral nerve demyelination

It has been speculated that beta-chemokines play a pivotal role in the development of peripheral nervous system (PNS) disorders characterized by mononuclear cell infiltration. In experimental allergic neuritis (EAN), an animal model for human Guillain-Barré syndrome (GBS) with mononuclear cell infiltration, we found by quantitative PCR that beta-chemokine messages were upregulated during the active stage. Moreover, an increase in the monocyte chemoattractant protein-1 (MCP-1) message was found in the preclinical stage of EAN, suggesting the critical role of MCP-1 for inducing mononuclear cell infiltrations in this model. Since many cell lineages other than immune cells can produce chemokines, this early upregulation of MCP-1 may be mediated by non-immune cells, probably endothelia or Schwann cells. To date, apart from MCP-1, only RANTES (Regulated on activation, normal T cell expressed and secreted) and macrophage inflammatory protein (MIP)-1alpha have been examined in EAN and found to have similar kinetics of induction. Therefore, understanding the regulation of production of these chemokines as well as mechanisms of inhibiting chemokine/receptor interactions in the PNS may ultimately lead to disease-specific therapy for GBS and related demyelinating disorders.     

Coeliac disease in Middle Eastern countries: a challenge for the evolutionary history of this complex disorder?

About 10,000 years ago domestication and farming of wheat and other cereals developed in the 'Fertile Crescent', an area including modern Turkey, Iraq and Iran. Agriculture then slowly spread from Middle East to Europe. Coeliac disease is the permanent intolerance to dietary gluten, the major protein component of wheat. It has been until relatively recently hypothesised that wheat consumption exerted a negative selective pressure on genes predisposing to coeliac disease, eventually leading to higher coeliac disease frequency in Northeastern Europe because of lack of exposure to cereals. This theory is at variance with recent studies showing that coeliac disease is as common in Middle Eastern countries as in Europe. High prevalence of coeliac disease has been found in Iran, in both the general population and at-risk groups, e.g. patients with irritable bowel syndrome or type 1 diabetes. Clinical manifestations of coeliac disease vary markedly with the age of the patient, the duration and the extent of disease. Clinical studies showed that presentation with non-specific symptoms or no symptoms is as common in the Middle East as in Europe. Wheat represented a major component of the Iranian diet for many centuries and it may be argued that the continuous and high level of exposure to wheat proteins has induced some degree of immune tolerance, leading to milder symptoms that may be misdiagnosed as irritable bowel syndrome or unexplained gastrointestinal disorders. The gluten-free diet represents a real challenge to both patients and clinicians in this area. This is particularly difficult in the absence of any supply for gluten-free diet in Middle Eastern countries.     

Psychometric properties of Persian version of the Caregiver Burden Scale in Iranian caregivers of patients with spinal cord injury

Purpose: To investigate the psychometric properties of the Persian version of Caregiver Burden Scale (CBS) in caregivers of patients with spinal cord injury.

Methods: This is a cross-sectional study. After a forward–backward translation, the CBS was administered to 110 caregivers of patients with spinal cord injury (men?=?60, women?=?50). Factor structure was evaluated by confirmatory factor analysis. The Internal consistency and test–retest reliability of the CBS were examined using Cronbach’s α and the intraclass correlation coefficient, respectively. Construct validity was assessed by examining the relationship among CBS and the World Health Organization Quality of Life, and the Beck Depression Inventory.

Results: The results of confirmatory factor analysis provided support for a five-factor model of CBS. All subscales of CBS revealed acceptable internal consistency (0.698–0.755), except for environment subscale (0.559). The CBS showed adequate test–retest reliability for its subscales (0.745–0.900). All subscales of CBS significantly correlated with both Beck Depression Inventory and World Health Organization Quality of Life, confirming construct validity.

Conclusions: The Persian version of the CBS is a valid and reliable measure for assessing burden of care in caregivers of patients with spinal cord injury.

• Implications for Rehabilitation

• Spinal cord injury leads to depression, high levels of stress and diminished quality of life due to the high physical, emotional, and social burdens in caregivers.

• Persian version of the Caregiver Burden Scale is a valid and reliable tool for assessing burden in Iranian caregivers of patients with spinal cord injury.

     

National nosocomial infection surveillance system-based study in Iran: additional hospital stay attributable to nosocomial infections

BACKGROUND: Nosocomial infection is a serious health and financial problem. The purpose of this study was to determine the extra hospital stay attributable to nosocomial infections for patients undergoing surgery. METHOD: All patients undergoing surgery admitted from March 1, 1999, to February 28, 2000, to the 38-bed general surgery ward within a university hospital in Shiraz, Iran, were included in this study. The study was planned as a pairwise-matched case-control study nested in cohort design. A case was defined as any patient with 1 of 4 of the following nosocomial infections: urinary tract infection; surgical site infection; bloodstream infection; or pneumonia, whereby definitions for the nosocomial infections were on the basis of National Nosocomial Infection Surveillance system definitions. For each patient, an appropriate match was selected, which resulted in 69 pairs of study patients. RESULTS: The total incidence of nosocomial infection during the study period was 17.59%. The mean extra length of hospitalization as a result of all major kinds of nosocomial infections was 6.62 days total, which was obtained using 4.4, 5.33, 8.73, and 9.2 extra days for urinary tract infection, pneumonia, surgical site infection, and bloodstream infection, respectively. CONCLUSION: Nosocomial infections add considerable costs to the health care system in Iran. Therefore, the development of strategies and concepts to reduce the incidence of nosocomial infections is cost-effective and warranted, and an appropriate surveillance system on the basis of international criteria is the cornerstone for this task.     

Immune tolerance induced by intravenous transfer of immature dendritic cells via up-regulating numbers of suppressive IL-10+ IFN-γ+-producing CD4+ T cells

Dendritic cells (DCs) regulate immunity and immune tolerance in vivo. However, the mechanisms of DC-mediated tolerance have not been fully elucidated. Here, we demonstrate that intravenous (i.v.) transfer of bone marrow-derived DCs pulsed with myelin oligodendrocyte glycoprotein (MOG) peptide blocks the development of experimental autoimmune encephalomyelitis in C57BL/6J mice. i.v. transfer of MOG-pulsed DCs leads to the down-regulation of the production of IL-17A and IFN-γ and up-regulation of IL-10 secretion. The development of regulatory T cells (Tregs) is facilitated via up-regulation of FoxP3 expression and production of IL-10. The number of suppressive CD4⁺IL-10⁺IFN-γ⁺ T cells is also improved. The expression of OX40, CD154, and CD28 is down-regulated, but the expression of CD152, CD80, PD-1, ICOS, and BTLA is up-regulated on CD4⁺ T cells after i.v. transfer of immature DCs. The expression of CCR4, CCR5, and CCR7 on CD4⁺ T cells is also improved. Our results suggest that immature DCs may induce tolerance via facilitating the development of CD4⁺FoxP3⁺ Tregs and suppressive CD4⁺IL-10⁺IFN-γ⁺ T cells in vivo.     

Genetic Characterization of Echinococcus granulosus from a Large Number of Formalin-Fixed,Paraffin-Embedded Tissue Samples of Human Isolates in Iran

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus, presents an important medical and veterinary problem globally, including that in Iran. Different genotypes of E. granulosus have been reported from human isolates worldwide. This study identifies the genotype of the parasite responsible for human hydatidosis in three provinces of Iran using formalin-fixed paraffin-embedded tissue samples. In this study, 200 formalin-fixed paraffin-embedded tissue samples from human CE cases were collected from Alborz, Tehran, and Kerman provinces. Polymerase chain reaction amplification and sequencing of the partial mitochondrial cytochrome c oxidase subunit 1 gene were performed for genetic characterization of the samples. Phylogenetic analysis of the isolates from this study and reference sequences of different genotypes was done using a maximum likelihood method. In total, 54.4%, 0.8%, 1%, and 40.8% of the samples were identified as the G1, G2, G3, and G6 genotypes, respectively. The findings of the current study confirm the G1 genotype (sheep strain) to be the most prevalent genotype involved in human CE cases in Iran and indicates the high prevalence of the G6 genotype with a high infectivity for humans. Furthermore, this study illustrates the first documented human CE case in Iran infected with the G2 genotype.