Challenges and Opportunities in Autoimmune Disease

Challenges and Opportunities in Autoimmune Disease

Millin, P. M., Klace, F., & Krieg, D. B. (2023)


The therapeutic effects of cannabis and its derivatives have been well established for a narrow number of conditions, including syndrome-related seizures, cancer-related nausea, and AIDS-related anorexia. Research progress in the United States has been slowed by restrictions related to cannabis’ status as a highly controlled substance. Despite the sluggish pace of empirical research, there is a high level of interest among both scientists and patients regarding cannabis’ possible efficacy for a much wider range of diseases and conditions. Studies indicate that many people are self-medicating with cannabis for both physical and psychological ailments. New evidence suggests that cannabinoids may be beneficial to those who have an autoimmune disease; this may be due to cannabis’ modulatory effects on the immune system. The current study, in an attempt to determine if college students with autoimmune diseases are self-medicating their symptoms with cannabis, surveyed students (5.8% of whom reported a diagnosed autoimmune disease) about their frequency, route of administration, and motivations for cannabis use. Independent samples t-tests and chi-squared tests revealed that while those with an autoimmune disease were significantly more likely to report having used cannabis in the past 30 days than their peers without an autoimmune disease, the frequency of use in the past 30 days did not differ. Participants with autoimmune disease were significantly more likely to endorse therapeutic motives for cannabis consumption, including pain and nausea control and to improve sleep and appetite. This study is one of the first to investigate self-medication motives for cannabis use in young adults with an autoimmune disease. Potential mechanisms, as well as benefits and drawbacks of cannabis use as medicine in this population are discussed.

Rosenthal, K. S., & Zimmerman, D. H. (2022)


Autoimmune disease disrupts the normal immunological balance by promoting a perpetual cycle of innate/immune/inflammatory responses that continues due to the continued presence of antigen. The disease cycle is in turn amplified and regulated by cycles of antigen-specific T cell mediated immune responses. Removal of the stimuli or regulation of the disease drivers can stop the cycle to allow rebalancing and prevent the progression or chronicity of disease. As an alternative to the current treatments for autoimmune and inflammatory disease, which reduce, inhibit or eliminate the triggers, drivers or antigens, newer approaches stimulate regulatory responses, or inhibit or repurpose the effector/inflammatory responses to control the immune disease cycle. LEAPS (Ligand Epitope Antigen Presentation System) therapeutic vaccines for rheumatoid arthritis are presented as examples of therapies that elicit antigen specific T cell modulation of autoimmune and inflammatory responses to treat disease.

Salinas, M., & Florenzano, M. (2021)


Interstitial lung diseases (ILD) are a complex and diverse group of disorders. ILD are more frequently diagnosed and prevalent now. In this article, diagnosis approach, including new bronchoscopy and genetic tools, and some recently added concepts are revisited, as progressive fibrosing interstitial lung diseases and interstitial lung abnormalities.

Recently information relative to idiopathic pulmonary fibrosis is shown, including genetics and pathophysiology. We look over the dynamic world of interstitial lung diseases related to connective tissue diseases, principal characteristics of this group and the principles that define which of the various available therapies should be chosen. Finally new concepts and guidelines published about the diagnosis and management of hypersensitivity pneumonitis are reported. New data and treatments have changed our traditional vision of these lung diseases and we will new options in the next years.

Tinguria, M. (2023)


Celiac disease (CD) is an immune mediated disorder characterised by intolerance to glutens in certain grains like whet, barley, and rye. The exposure to gliadin protein component in the susceptible individuals leads to an inflammatory reaction damaging small bowel mucosa with progressive disappearance of intestinal villi. The damaged intestinal mucosa leads to malabsorption. The usual symptoms of celiac disease include diarrhea, steatorrhea, weight loss, fatigue, and abdominal pain. Diagnosis is based on clinical features, duodenal biopsy, elevated levels of anti-gliadin antibodies and response to gluten free diet. Contrary to common belief, celiac disease is a protein systemic disease rather than merely a pure digestive alteration. Celiac disease is closely associated with genes that code HLA -II antigens mainly of DQ2 and DQ8 classes, production of disease specific antibodies (i.e., endomysial antibodies), multiorgan involvement, comorbidity with other autoimmune diseases (shared autoimmunity), familial aggregation, and immune system dysregulation.

The clinical presentation of celiac disease can be variable. In mild form, patients can be almost asymptomatic whereas in the most severe form, the patients are at increased risk of life-threatening complications. Celiac disease has a well-known association with other autoimmune diseases such as autoimmune liver diseases (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis), diabetes mellitus, autoimmune thyroid diseases, skin diseases such as dermatitis herpetiformis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, psoriasis, sarcoidosis, immune thrombocytopenic purpura, and pancreatitis. In addition, celiac disease may be associated with rare but potentially serious complications such as, collagenous sprue, ulcerative jejunoileitis, refractory celiac disease (RCD), enteropathy associated T-cell lymphoma, small bowel adenocarcinoma (SBA), hyposplenism, and cavitating mesenteric lymph node syndrome (CMLNS). The present article describes clinicopathologic features of these rare but serious complications of celiac disease.

Nozawa, K. (2017)


Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by damage to multiple organs caused by systemic autoimmunity. One of the characteristic features in SLE is the presence of numerous autoantibodies. Although certain autoantibodies such as anti-double strands DNA antibodies are known to be pathological, the correlation between many autoantibodies and tissue damage in patients with SLE remains unclear. Although the prognosis for survival in patients with SLE has improved dramatically in recent decades, its neuropsychiatric complications remain a major cause of morbidity. The neuropsychiatric manifestations can be attributed to SLE itself and are referred to as neuropsychiatric SLE (NPSLE). Multiple factors are involved in the pathogenesis of NPSLE including the genetic background, vasoculopathy, autoantibodies, and inflammatory mediators associated with SLE. However, neuropsychiatric manifestations can also be caused by other factors not associated with SLE, including steroid psychosis, infectious diseases, and metabolic factors. Therefore, NPLSE can be diagnosed in patients with SLE only if other causes have been excluded; difficulty in diagnosing NPSLE often occurs in many cases.

Various potential biomarkers for the diagnosis of NPSLE have been reported. However, useful and practical diagnostic biomarkers with high specificity for NPSLE have not been established to date. This review summarized the current data on autoantibodies recognized in NPSLE, and described their diagnostic value and pathogenic roles.

Ammouri, W., Harmouche H., Hajar, K., Mouna, M., Zoubida, M., & Mohamed, A. (2022). 


Macrophage activation syndrome can be primary with a genetic etiology, or secondary, associated with malignancies, infections or systemic diseases. Its a severe and potentially life-threatening complication of autoimmune diseases. The incidence of MAS among patients with systemic lupus erythematosus is not well known, as most of the previous studies were limited to a small number of case series or case reports. In recent years it has been suggested that macrophage activation syndrome in systemic lupus erythemaosus may be underrecognized because it can mimic the clinical features of the underlying disease or be confused with an infectious complication. The diagnosis of macrophage activation sydrome in adults is supported by hyperferritinemia (higher than 2000 ng/ml), and/or splenomegaly, pronounced cytopenias, hypofibrinogenemia, characteristic cytokine profile and hypertriglyceridemia. In the case of systemic lupus erythematosus flare, hyerferritinemia is the strongest indicator to differentiate them from MAS. So far, no validated and universally embraced diagnostic criteria for macrophage activation syndrome in adult secondary to systemic lupus erythematosus are available. It is important to know the parameters that can guide the clinician towards the diagnosis of macrophage activation syndrome in adult with systemic lupus. Early diagnosis and intensive therapy are essential in improving clinical outcomes. Hence, we decided to write this mini- review to focus on the demographic data, on the pathophysiological mechanisms, clinical and laboratory manifestations, treatments, and outcomes of patients with systemic lupus erythematosus associated macrophage activation syndrome.

Mweetwa, L. L., Mampane, T., Kenaope, T., Mosala, B., Pule, K., Obure, G., & Mothibe, G. (2022). 


Nanobiotechnology is a multi-strategic approach that engineers biological components (atoms and molecules) at the nanoscales. The concept was introduced as an effective alternative with drug delivery and targeting properties. Nanobiotechnology has several applications in cancerous disease, autoimmune, inflammation, infectious, and viral diseases, and for the management of COVID-19. Nanoparticles have biomimetic properties, encapsulation, and safety formulation of drugs, and all these properties give them an advantage over conventional drug strategies. Nanobiotechnology research is currently progressive and needs extensive exploration and understanding for its potential use in future innovations. The present review studied the concept of nanobiotechnology, its origin, mechanism of drug delivery and targeting, applications, and future perspective in pharmacology and innovation to decipher its role in future advanced research.

Figueiredo, I., Martins, M., Midões, C., & Ferrão, J. (2022). 


Opportunistic infections affect patients with immunocompromised status and are caused by common microorganisms with more severe presentations, or atypical organisms that do not cause disease in the immunocompetent. The type of infection varies with the type of immune dysfunction.

Patients with cell-mediated immune dysfunction tend to be infected with a range of viral infections, intracellular bacteria, and fungi. This contrasts to patients with defects in humoral immunity, where infections with encapsulated bacteria, and enteric organisms such Giardia lamblia and enteroviruses predominate. Patients with phagocytic defects are especially prone to infections with Gram-negative bacteria and fungi, whilst those with complement disorders are prone to recurrent infections with encapsulated bacteria. In contrast to patients with primary immunodeficiencies, which usually present with only one defect of the above, acquired immunodeficiencies present with a variety of those, and clinical presentations are diversified.

The epidemic of HIV and AIDS shed some light into infections that were before extremely rare, by making them frequent, but with the advent of anti-retroviral therapy their clinical presentation has shifted. Also, the emergence of novel immunotherapies for cancer and autoimmune diseases, allied with an increase in organ transplant has increased the pool of immunosuppressed patients without HIV, which present differently regarding opportunist infections.

Rapid and specific microbiologic diagnosis is essential. Newer microbiologic assays have improved the diagnosis and management of opportunistic infections.

Our aim was to revise and summarize the most frequent opportunist infections, and how their presentation and course compares in different immunosuppressed diseases (HIV and non-HIV).

Plum, L. A., & DeLuca, H. (2023). 


The inverse relationship of multiple sclerosis (MS) to sunlight exposure was proposed at least 50 years ago but conclusive evidence is unavailable.  Since the proposal was made, many researchers have jumped to the conclusion vitamin D mediates this effect. Vitamin D is a pro-hormone produced in the skin by UV irradiation and/or sun exposure.   In addition, an inverse relationship between plasma levels of the vitamin D metabolite, 25(OH)D3, and a reduced incidence of MS has been noted.  As a result of the relationship clinical trials have been carried out to determine if vitamin D supplementation can suppress the disease. The results have not supported this idea. In an animal model of MS (experimental autoimmune encephalomyelitis or EAE) the vitamin D hypothesis was refuted.  UV irradiation, on the other hand, consistently reduces the incidence and severity of EAE.  Because EAE is a widely accepted model of human MS, clinical trials testing the efficacy of the narrow band UV light in suppression of MS appear warranted. If in fact this narrow band light does suppress human MS, isolation and identification of the compound produced by this light should be initiated.

Mohammad, A., & Carpenter, D. O. (2022). 


Rheumatoid arthritis is an autoimmune disease, while osteoarthritis is presumed to be a disease due to wear and tear causing damage to joints.  Some environmental exposures, such as smoking, air pollution and possibly persistent organic pollutants, are known to increase the risk of both.  We have utilized the National Health and Nutrition Examination Survey (NHANES) data to determine associations between self-reported prevalence of any form of arthritis, rheumatoid and osteoarthritis and various polychlorinated biphenyl (PCB) congeners, several chlorinated pesticides and 2.3,7,8-tetrachloro-dibenzo-dioxin (TCDD).  We find that there is a statistically significant association between serum PCB levels of more highly chlorinated PCB congeners and both types of arthritis.  The associations are stronger with rheumatoid arthritis than with osteoarthritis, and stronger in women than in men. 

Sneha, B., Lauren, G., & Langston, C. (2023). 


Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that is characterized by recurrent bouts of acute neuroinflammation and chronic neurodegeneration. Treatments for MS are aimed at prevention of disability in the future or restoring function in the present. Prevention treatments disrupt the underlying disease pathology, whereas restorative treatments address not only the disease’s primary effects on the central nervous system, but also secondary effects on other parts of the body and tertiary effects on each patient’s psychosocial functioning. MS symptoms can have primary, secondary, and tertiary components, which can interlock and reinforce each other. Restorative treatment should tease apart these components and address them separately. In this article on symptom management, we focus on treatments that aim to maximize each component of function.

Jensen, A. D., & Seiff, S. R. (2023). 


Thyroid-associated orbitopathy (TAO) is a disfiguring and in severe cases debilitating autoimmune disease that has been the subject of much recent drug development and investigation. This condition is characterized by an acute inflammatory phase followed by a resolving, cicatricial phase. There has been a search to find an effective agent to address the acute inflammatory phase of this disease, which would hopefully minimize end stage disfigurement, overall morbidity, and the need for surgery. The advent of antibody-based immunologic therapies has shown promise in this regard. Herein we discuss the current biologic therapeutic landscape, including agents targeting the insulin-like growth factor-1 receptor (IGF-1R, teprotumumab) and the interleukin-6 receptor (IL-6R, tocilizumab), and provide additional insight and opinion from our group practice that is highly experienced in treating a large number of TAO patients. Notably, though teprotumumab is effective, and we regularly prescribe this agent with good success, we feel that tocilizumab should be regarded as another first-line therapy that may be a more appropriate choice for certain patients with active inflammatory TAO.

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