A proposed role of human defensins in Helicobacter pylori-related neurodegenerative disorders.

Cationic host defence peptides (CHDPs), also known as antimicrobial peptides (AMPs), are essential components of the innate immunity with antimicrobial and pleiotropic immunomodulatory properties. In mammals the two major families of CHDPs are defensins and cathelicidins that comprise an arsenal of innate regulators of principal importance in the host tissues. Research in the last decade has demonstrated that defensins are crucial effectors of both innate and adaptive immunity. Defensins can modulate immune responses, either by stimulation or suppression, thereby controlling inflammatory processes and infections. Currently only few data, mostly hypothetical, focus on the role of defensins in central nervous system (CNS) physiopathology and neurodegeneration. Defensins may function as an initial line of defense within the CNS either as an antimicrobial, immunomodulator, or both. A dysregulation of brain expression of specific defensins might either exacerbate or ameliorate the inflammatory response within the CNS depending upon which extracellular conditions predominate. It is proposed that reduction or abnormal elevation of AMP expression by cerebral microglia, astrocytes or choroid plexus epithelium might contribute to loss of AMP-induced regulation of immune responses, thereby promoting neuronal cell injury and death observed in Alzheimer's disease and possibly in other neurodegenerative disorders. Nevertheless, whether certain AMPs play a crucial role in the onset or promotion of the neuroinflammatory process and neurodegeneration is currently unknown, thereby emphasizing the necessity of further investigation into the regulatory mechanisms that control innate and adaptive immunity within the brain. Recent data indicate that Helicobacter pylori (H. pylori) induces defensins' release associated with chronic inflammatory tissue damage. However, it remains unclear whether and how H. pylori evades the attack by defensins. Moreover, recent evidence indicates that H. pylori infection might contribute to the pathogenesis of neurodegenerative diseases, by releasing several inflammatory mediators that could induce blood-brain barrier breakdown, thereby being involved in the pathogenesis of neurodegeneration. However, currently there are no data regarding the potential impact of human defensins on H. pylori-related neurodegenerative disorders. We herein propose that human defensins might contribute to the pathophysiology of H. pylori-related neurodegenerative disorders by modulating variably innate and adaptive immune system responses. Better understanding of the mechanisms regarding human defensins' possible involvement in H. pylori-induced neurodegeneration might help develop novel therapeutic strategies against H. pylori-related neurodegenerative disorders.

Multiple sclerosis, idiopathic dilated cardiomyopathy, and insulin-dependent diabetes mellitus: a common mechanism of irregular immune regulation.

BACKGROUND: Multiple sclerosis (MS), idiopathic dilated cardiomyopathy (DCM), and diabetes mellitus-1 (DM-1) are polygenic autoimmune diseases with a pivotal autoimmune component affecting young adults. They share a number of characteristics, thereby suggesting common underlying pathways or mechanisms. Typically, the aforementioned diseases are organ-specific autoimmune disorders of unknown etiology, but with strong evidence of tissue-destructive activity of the humoral and/or cellular immune system in the end-organ tissues affected (ie, the myelin components in MS, the myocytes of myocardium in DCM, and the insulin-secreting ß islets in DM-1). CASE REPORT: We herein describe a 35-year-old white Greek man who presented with coexisting MS, DCM, and DM-1 diagnosed over a period of 7 years. The patient was successfully treated and is asymptomatic until present time. CONCLUSION: The clustering of these 3 autoimmune diseases in our patient supports the concept of an immune-mediated damage in these diseases, an important aspect for an effective therapeutic choice by neurologists. However, the immunopathogenetic association between MS and other autoimmune remains speculative, thereby warranting further clarification.

Five-year survival after Helicobacter pylori eradication in Alzheimer disease patients.

BACKGROUND: Alzheimer disease (AD) is a progressive, fatal neurodegenerative condition. OBJECTIVE: We tested the hypothesis that eradication of Helicobacter pylori infection (Hp-I) could improve survival in a Greek cohort of AD patients, in a 5-year follow-up. METHOD: Forty-six patients diagnosed with probable AD were enrolled in the analysis. Study population was classified into 3 groups: patients for whom Hp eradication treatment was successful; those for whom eradication of Hp had failed, they refused, and/or were noncompliant with eradication therapy; and those who were Hp negative at baseline. Cox proportional hazards model was built with all-cause mortality as the dichotomous outcome. RESULTS: During the 5-year follow-up [47.19±15.11 mo (range 12 to 60)], overall 21 patients died and 25 patients remained alive. Patients who died were older and exhibited lower mean MMSE score compared with the patients still alive. Successful eradication of Hp-I was associated with a significantly lower mortality risk [HR (95% CI)=0.287 (0.114-0.725), P=0.008]. The results were similar in adjusted and unadjusted models, for age and MMSE at baseline. CONCLUSION: Hp eradication regimen in AD patients is associated with a higher 5-year survival rate.