autoimmune conditions
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2022 ◽  
Vol 11 (2) ◽  
pp. 394
Author(s):  
Maria Paola Lauretta ◽  
Rita Maria Melotti ◽  
Corinne Sangermano ◽  
Anneliya Maria George ◽  
Rafael Badenes ◽  
...  

Background: Hyperhomocysteinemia (HHcy) is considered as an independent risk factor for several diseases, such as cardiovascular, neurological and autoimmune conditions. Atherothrombotic events, as a result of endothelial dysfunction and increased inflammation, are the main mechanisms involved in vascular damage. This review article reports clinical evidence on the relationship between the concentration of plasmatic homocysteine (Hcy) and acute brain injury (ABI) in neurocritical care patients. Materials and methods: a systematic search of articles in the PubMed and EMBASE databases was conducted, of which only complete studies, published in English in peer-reviewed journals, were included. Results: A total of 33 articles, which can be divided into the following 3 subchapters, are present: homocysteine and acute ischemic stroke (AIS); homocysteine and traumatic brain injury (TBI); homocysteine and intracranial hemorrhage (ICH)/subarachnoid hemorrhage (SAH). This confirms that HHcy is an independent risk factor for ABI and a marker of poor prognosis in the case of stroke, ICH, SAH and TBI. Conclusions: Several studies elucidate that Hcy levels influence the patient’s prognosis in ABI and, in some cases, the risk of recurrence. Hcy appears as biochemical marker that can be used by neuro-intensivists as an indicator for risk stratification. Moreover, a nutraceutical approach, including folic acid, the vitamins B6 and B12, reduces the risk of thrombosis, cardiovascular and neurological dysfunction in patients with severe HHcy that were admitted for neurocritical care.


2022 ◽  
Vol 81 (1) ◽  
Author(s):  
Roland Hӧllhumer

Background: Peripheral ulcerative keratitis (PUK) is a severe inflammatory disease of the peripheral cornea that can be caused by local factors or systemic inflammatory disease.Aim: The purpose of this review is to give an overview of the pathophysiology, aetiology, clinical features, diagnosis, and management of PUK.Method: A PubMed search was conducted using the keywords, ‘peripheral ulcerative keratitis’ and ‘Mooren’s ulcer’.Results: The peripheral cornea has unique characteristics the predispose to the development of PUK. These include fine capillary arcades that allow for deposition of immune complexes and subsequent activation of an inflammatory cascade with corneal melt. Several conditions have been implicated in the aetiology of PUK. The most commonly cited causes are rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA) and various dermatoses. In patients with RA, PUK usually presents in established disease, whereas in GPA, PUK may be the presenting feature in up to 60% of cases. In RA it heralds the onset of a systemic vasculitis with significant associated morbidity and mortality. The management of PUK follows an individualised stepwise approach. All patients require supportive measures to encourage healing and halt the process of keratolysis. Systemic autoimmune conditions need a systemic corticosteroid as a fast-acting agent to halt the inflammatory process while cytotoxic therapy maintains long term disease control. Failure to achieve disease control with CTT, necessitates the use of a biologic agent.Conclusion: Peripheral ulcerative keratitis is a severe inflammatory disease of the peripheral cornea that needs a thorough diagnostic workup and stepwise management approach.


2022 ◽  
Vol 0 ◽  
pp. 1-8
Author(s):  
Abel Francis ◽  
Anjali Rose Jose

Immunosuppressive drugs are the main stay of treatment for autoimmune dermatoses. The main disadvantage of these drugs is the increased susceptibility to life-threatening infections. Hence, in recent years, there has been an enthusiastic search for newer groups of drugs that can reduce this risk. Immune enhancing agents are considered as the key players of future. Immune enhancers function by activating various elements of the immune system and thereby amplifying the immune responses. They can be specific or non-specific in action. The main autoimmune dermatoses where the benefits of these drugs have so far been utilized include alopecia areata, vitiligo, psoriasis, lichen planus, and discoid lupus erythematosus. Immunostimulants are available in both topical and systemic forms. Topical immune- enhancing agents include contact sensitizers (diphenylcyclopropenone, dinitrochlorobenzene, and squaric acid dibutyl ester), anthralin, topical zinc, and interferons. Systemic agents include levamisole, zinc, probiotics, and so on. The exact mechanism of action of some of these drugs and other autoimmune conditions where they can be benefited is not completely understood. Another therapeutic agent that may come up in the future is individualized vaccines. Let us look forward to the days when individualized vaccines work wonders in the management of autoimmune diseases.


2022 ◽  
Vol 12 ◽  
Author(s):  
Leila Abdelhamid ◽  
Xin M. Luo

The immune system is an efficiently toned machinery that discriminates between friends and foes for achieving both host defense and homeostasis. Deviation of immune recognition from foreign to self and/or long-lasting inflammatory responses results in the breakdown of tolerance. Meanwhile, educating the immune system and developing immunological memory are crucial for mounting defensive immune responses while protecting against autoimmunity. Still to elucidate is how diverse environmental factors could shape autoimmunity. The emergence of a world pandemic such as SARS-CoV-2 (COVID-19) not only threatens the more vulnerable individuals including those with autoimmune conditions but also promotes an unprecedented shift in people’s dietary approaches while urging for extraordinary hygiene measures that likely contribute to the development or exacerbation of autoimmunity. Thus, there is an urgent need to understand how environmental factors modulate systemic autoimmunity to better mitigate the incidence and or severity of COVID-19 among the more vulnerable populations. Here, we discuss the effects of diet (macronutrients and micronutrients) and hygiene (the use of disinfectants) on autoimmunity with a focus on systemic lupus erythematosus.


2022 ◽  
Vol 14 (1) ◽  
pp. e2022011
Author(s):  
SIMONA BIANCHI ◽  
ALESSIA ANGI ◽  
MAURO PASSUCCI ◽  
GIOVANNA PALUMBO ◽  
ERMINIA BALDACCI ◽  
...  

Rare cases of immune thrombocytopenia (ITP) occurring after SARS-CoV-2 mRNA vaccines have recently reached public attention. It has been reported in patients with previous ITP or other autoimmune diseases and in individuals with an apparent negative past medical history.  The management and the outcome of these cases are still not well investigated and reported in the medical literature. A 23-year-old female with a past medical history of ITP, in stable complete remission for 3 years and on mycophenolate treatment received SARS-CoV-2 mRNA vaccine. She presented severe ITP recurrence with hemorrhagic symptoms after the second vaccine dose. A combined treatment with high-dose immunoglobulin and prednisone was successfully administered with a full recovery of platelet count. The patient remains in ITP remission and on mycophenolate therapy, five months later. At our Center, none of the other 76 adult “fragile patients” with ITP on immunosuppressive treatment who had received the SARS-CoV-2 mRNA vaccine, developed such a severe thrombocytopenic recurrence. Follow-up of large cohorts of patients receiving mRNA vaccine will answer the question as to whether it increases the risk of autoimmune conditions. So far, the benefits of the vaccination largely outweigh the risk of infection in these patients.


2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Minkyo Song ◽  
M. Constanza Camargo ◽  
Andriy Derkach ◽  
Charles S. Rabkin ◽  
Eric A. Engels

2021 ◽  
Vol 23 (1) ◽  
pp. 408
Author(s):  
Andrea Arena ◽  
Eugenia Belcastro ◽  
Antonella Accardo ◽  
Annamaria Sandomenico ◽  
Olivia Pagliarosi ◽  
...  

Autoimmune endocrine disorders, such as type 1 diabetes (T1D) and thyroiditis, at present are treated with only hormone replacement therapy. This emphasizes the need to identify personalized effective immunotherapeutic strategies targeting T and B lymphocytes. Among the genetic variants associated with several autoimmune disorders, the C1858T polymorphism of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, encoding for Lyp variant R620W, affects the innate and adaptive immunity. We previously exploited a novel personalized immunotherapeutic approach based on siRNA delivered by liposomes (lipoplexes) that selectively inhibit variant allele expression. In this manuscript, we improved lipoplexes carrying siRNA for variant C1858T by functionalizing them with Fab of Rituximab antibody (RituxFab-Lipoplex) to specifically target B lymphocytes in autoimmune conditions, such as T1D. RituxFab-Lipoplexes specifically bind to B lymphocytes of the human Raji cell line and of human PBMC of healthy donors. RituxFab-Lipoplexes have impact on the function of B lymphocytes of T1D patients upon CpG stimulation showing a higher inhibitory effect on total cell proliferation and IgM+ plasma cell differentiation than the not functionalized ones. These results might open new pathways of applicability of RituxFab-Lipoplexes, such as personalized immunotherapy, to other autoimmune disorders, where B lymphocytes are the prevalent pathogenic immunocytes.


2021 ◽  
Vol 12 ◽  
Author(s):  
James K. Fields ◽  
Kyle Kihn ◽  
Gabriel S. Birkedal ◽  
Erik H. Klontz ◽  
Kjell Sjöström ◽  
...  

Interleukin-1 (IL-1) family cytokines are potent mediators of inflammation, acting to coordinate local and systemic immune responses to a wide range of stimuli. Aberrant signaling by IL-1 family cytokine members, however, is linked to myriad inflammatory syndromes, autoimmune conditions and cancers. As such, blocking the inflammatory signals inherent to IL-1 family signaling is an established and expanding therapeutic strategy. While several FDA-approved IL-1 inhibitors exist, including an Fc fusion protein, a neutralizing antibody, and an antagonist cytokine, none specifically targets the co-receptor IL-1 receptor accessory protein (IL-1RAcP). Most IL-1 family cytokines form productive signaling complexes by binding first to their cognate receptors – IL-1RI for IL-1α and IL-1β; ST2 for IL-33; and IL-36R for IL-36α, IL-36β and IL-36γ – after which they recruit the shared secondary receptor IL-1RAcP to form a ternary cytokine/receptor/co-receptor complex. Recently, IL-1RAcP was identified as a biomarker for both AML and CML. IL-1RAcP has also been implicated in tumor progression in solid tumors and an anti-IL1RAP antibody (nadunolimab, CAN04) is in phase II clinical studies in pancreatic cancer and non-small cell lung cancer (NCT03267316). As IL-1RAcP is common to all of the abovementioned IL-1 family cytokines, targeting this co-receptor raises the possibility of selective signaling inhibition for different IL-1 family cytokines. Indeed, previous studies of IL-1β and IL-33 signaling complexes have revealed that these cytokines employ distinct mechanisms of IL-1RAcP recruitment even though their overall cytokine/receptor/co-receptor complexes are structurally similar. Here, using functional, biophysical, and structural analyses, we show that antibodies specific for IL-1RAcP can differentially block signaling by IL-1 family cytokines depending on the distinct IL-1RAcP epitopes that they engage. Our results indicate that targeting a shared cytokine receptor is a viable therapeutic strategy for selective cytokine signaling inhibition.


2021 ◽  
Vol 31 (6) ◽  
pp. 816-821
Author(s):  
Alexandr V. Averyanov ◽  
Anastasia S. Perkina

Common variable immunodeficiency (CVID) is a rare immunodeficiency, the classic manifestation being recurrent infections. Other lesions are often found in CVID patients, such as malignant neoplasms, autoimmune conditions caused by abnormal cellular immunity, in addition to infectious complications. Usually, the pathological process involves the lungs. This article presents a clinical case of a patient with CVID complicated by granulomatous lymphocytic interstitial lung disease.


2021 ◽  
Vol 12 ◽  
Author(s):  
Luke A. Moradi ◽  
Curtis A. Clark ◽  
Craig S. Schneider ◽  
Alok S. Deshane ◽  
Michael C. Dobelbower

Immune checkpoint inhibitors (ICIs) and radiotherapy (RT) combinations for various metastatic cancers are increasingly utilized, yet the augmentation of anti-cancer immunity including distant tumor responses by RT remains ill-characterized. Immunosuppressive tumor microenvironments and defective anti-tumor immune activation including immune-related adverse events (irAEs) likely limit dramatic immuno-radiotherapy combinations, though it remains unclear which immune characteristics mediate dramatic systemic tumor regression in only a small subset of patients. Moreover, the efficacy of ICI treatment in patients receiving immunosuppressive therapies for autoimmune conditions or irAEs is convoluted, yet clinically valuable. Here, we report a case of a 75-year-old man with myasthenia gravis and metastatic melanoma who experienced complete and durable systemic regression after receiving pembrolizumab and single-lesion RT while on prednisone for myasthenia gravis prophylaxis and vedolizumab for immune-mediated colitis after previously experiencing mixed response on pembrolizumab monotherapy. We discuss the potential paradoxical effects and clinical considerations of immunosuppressive regimens in patients with underlying autoimmune disease or adverse immune reactions while receiving immuno-radiotherapy combinations.


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