BCG and Autoimmunity

The bacillus Calmette-Guérin (BCG) is a live, attenuated vaccine from Mycobacterium bovis obtained by Albert Calmette and Camille Guerin through 230 in vitro passages between 1908 and 1921. This chapter presents clinical applications of BCG such as tuberculosis, leprosy, asthma and other hypersensitivity diseases, Type 1 diabetes, multiple sclerosis, and cancer. BCG can be described as a “double-acting tool” because its own immunogenicity produces a preventive effect in a variety of diseases and may trigger a number of autoimmune phenomena. An acute inflammatory polyarthritis with skin maculopapular rash was reported in a healthy woman following intradermal BCG. Side effects such as granulomatous pneumonia and hepatitis are reported without sufficient data to support the possible link with intravesical BCG and the autoimmune mechanism. Even the kidney may be the target of hypersensitivity reaction to intravesical BCG, which can induce an interstitial nephritis with non-necrotizing, sterile granulomas responsive to steroid therapy

Diagnosis of childhood tuberculosis and host RNA expression in Africa

Improved diagnostic tests for tuberculosis in children are needed. We hypothesized that transcriptional signatures of host blood could be used to distinguish tuberculosis from other diseases in African children who either were or were not infected with the human immunodeficiency virus (HIV

Neurocutanoussarcoidosis: a rare entity

Neurosarcoidosis is a granulomatous disorder considered to be a great imitator. We report a case of young lady who presented with gradual onset flexed posturing of fingers of left hand for four years, followed by similar pattern of weakness involving the right hand for three years along with slipping of slippers for one year. Neurologic examination showed distal wasting & weakness in upper limbs with normal jerks and sensory impairment in gloves and stocking distribution. On skin examination there were hypopigmented macules over face, neck and back. Electro diagnostic studies showed sensory motor axonal polyneuropathy, while skin biopsy reported as naked noncaseating granulomas suggestive of sarcoidosis. No such case reported yet in Pakistan with sarcoidperipheral polyneuropathy and rare hypopigmented form of Sarcoidosis without pulmonary involvement

Klotho pathways, myelination disorders, neurodegenerative diseases, and epigenetic drugs

In this review we outline a rationale for identifying neuroprotectants aimed at inducing endogenous Klotho activity and expression, which is epigenetic action, by definition. Such an approach should promote remyelination and/or stimulate myelin repair by acting on mitochondrial function, thereby heralding a life-saving path forward for patients suffering from neuroinflammatory diseases. Disorders of myelin in the nervous system damage the transmission of signals, resulting in loss of vision, motion, sensation, and other functions depending on the affected nerves, currently with no effective treatment. Klotho genes and their single-pass transmembrane Klotho proteins are powerful governors of the threads of life and death, true to the origin of their name, Fates, in Greek mythology. Among its many important functions, Klotho is an obligatory co-receptor that binds, activates, and/or potentiates critical fibroblast growth factor activity. Since the discovery of Klotho a little over two decades ago, it has become ever more apparent that when Klotho pathways go awry, oxidative stress and mitochondrial dysfunction take over, and age-related chronic disorders are likely to follow. The physiological consequences can be wide ranging, potentially wreaking havoc on the brain, eye, kidney, muscle, and more. Central nervous system disorders, neurodegenerative in nature, and especially those affecting the myelin sheath, represent worthy targets for advancing therapies that act upon Klotho pathways. Current drugs for these diseases, even therapeutics that are disease modifying rather than treating only the symptoms, leave much room for improvement. It is thus no wonder that this topic has caught the attention of biomedical researchers around the world.https://www.liebertpub.com/doi/10.1089/biores.2020.0004Published versio

Serum levels of soluble forms of T cell activation antigens CD27 and CD25 in systemic lupus erythematosus in relation with lymphocytes count and disease course

Systemic lupus erythematosus (SLE) patients are characterized by a low lymphocyte count, which is considered a specific disease marker and is related to disease activity. The membrane bound molecules CD25 and CD27 are expressed and released in a soluble CD25 (sCD25) and soluble CD27 (sCD27) form by activation of predominantly T cells. In previous studies it was claimed that sCD25 as well sCD27 might be used as parameters for activation of the immune system; a correlation between the sCD25 profile with the disease course in SLE patients was also shown. To assess the relationship between lymphocyte count and these T cell activation markers, we performed a cross-sectional and a longitudinal study. In the longitudinal study three SLE patients who were known for a long time at our outpatient clinic were studied. Both T cell markers strongly correlated with each other and formed a reflection of the disease course. In all 7 periods of exacerbation, which we observed in the 3 investigated patients, both levels increased preceding this period; however, no correlation was found with the lymphocyte count. In the cross sectional study of 69 patients with SLE, sCD25 and sCD27 levels were correlated with defined disease manifestations; sCD25 was elevated in all periods of increased disease activity. The same holds true for sCD27, with the exception of patients with nephritis in which the highest levels were observed. Both profiles of sCD25 and sCD27 were strongly correlated during the whole disease course. Our data prove that in the pathogenesis of SLE an active recruitement of unprimed and primed T cells takes place

Emerging roles of pathogens in Alzheimer disease

Chronic spirochetal infection can cause slowly progressive dementia, cortical atrophy and amyloid deposition in the atrophic form of general paresis. There is a significant association between Alzheimer disease (AD) and various types of spirochete (including the periodontal pathogen Treponemas and Borrelia burgdorferi), and other pathogens such as Chlamydophyla pneumoniae and herpes simplex virus type-1 (HSV-1). Exposure of mammalian neuronal and glial cells and organotypic cultures to spirochetes reproduces the biological and pathological hallmarks of AD. Senile-plaque-like beta amyloid (Aβ) deposits are also observed in mice following inhalation of C. pneumoniae in vivo, and Aβ accumulation and phosphorylation of tau is induced in neurons by HSV-1 in vitro and in vivo. Specific bacterial ligands, and bacterial and viral DNA and RNA all increase the expression of proinflammatory molecules, which activates the innate and adaptive immune systems. Evasion of pathogens from destruction by the host immune reactions leads to persistent infection, chronic inflammation, neuronal destruction and Aβ deposition. Aβ has been shown to be a pore-forming antimicrobial peptide, indicating that Aβ accumulation might be a response to infection. Global attention and action is needed to support this emerging field of research because dementia might be prevented by combined antibiotic, antiviral and anti-inflammatory therap

LRRK2 and neuroinflammation: Partners in crime in Parkinson's disease?

3noopenopenRusso, Isabella*; Bubacco, Luigi; Greggio, ElisaRusso, Isabella; Bubacco, Luigi; Greggio, Elis

Alzheimer's disease immunization strategies : a review of current research

Scholarly project (M.S.)

“Bridging the Gap” Everything that Could Have Been Avoided If We Had Applied Gender Medicine, Pharmacogenetics and Personalized Medicine in the Gender-Omics and Sex-Omics Era

Gender medicine is the first step of personalized medicine and patient-centred care, an essential development to achieve the standard goal of a holistic approach to patients and diseases. By addressing the interrelation and integration of biological markers (i.e., sex) with indicators of psychological/cultural behaviour (i.e., gender), gender medicine represents the crucial assumption for achieving the personalized health-care required in the third millennium. However, ‘sex’ and ‘gender’ are often misused as synonyms, leading to frequent misunderstandings in those who are not deeply involved in the field. Overall, we have to face the evidence that biological, genetic, epigenetic, psycho-social, cultural, and environmental factors mutually interact in defining sex/gender differences, and at the same time in establishing potential unwanted sex/gender disparities. Prioritizing the role of sex/gender in physiological and pathological processes is crucial in terms of efficient prevention, clinical signs’ identification, prognosis definition, and therapy optimization. In this regard, the omics-approach has become a powerful tool to identify sex/genderspecific disease markers, with potential benefits also in terms of socio-psychological wellbeing for each individual, and cost-effectiveness for National Healthcare systems. “Being a male or being a female” is indeed important from a health point of view and it is no longer possible to avoid “sex and gender lens” when approaching patients. Accordingly, personalized healthcare must be based on evidence from targeted research studies aimed at understanding how sex and gender influence health across the entire life span. The rapid development of genetic tools in the molecular medicine approaches and their impact in healthcare is an example of highly specialized applications that have moved from specialists to primary care providers (e.g., pharmacogenetic and pharmacogenomic applications in routine medical practice). Gender medicine needs to follow the same path and become an established medical approach. To face the genetic, molecular and pharmacological bases of the existing sex/gender gap by means of omics approaches will pave the way to the discovery and identification of novel drug-targets/therapeutic protocols, personalized laboratory tests and diagnostic procedures (sex/gender-omics). In this scenario, the aim of the present review is not to simply resume the state-of-the-art in the field, rather an opportunity to gain insights into gender medicine, spanning from molecular up to social and psychological stances. The description and critical discussion of some key selected multidisciplinary topics considered as paradigmatic of sex/gender differences and sex/gender inequalities will allow to draft and design strategies useful to fill the existing gap and move forward