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Autoimmunity seems to be present in a large proportion of women with spontaneous premature ovarian insufficiency (POI). Whether these women are at increased risk for autoimmune disease has not been determined to date. Therefore, the aim of this study was to investigate a large series of antibodies in order to shed more light into the autoimmune risk of POI women. In a prospective case–control study, blood samples from 66 patients with spontaneous POI and 66 healthy controls were analyzed for a series of autoimmune antibodies. POI women revealed significantly increased thyroglobulin antibodies (TGAb) (p = 0.045) and thyroid peroxidase antibodies (TPOAb) (p = 0.002). At least one abnormal autoimmune parameter was present in 37.9% of POI women, compared to 18.2% in healthy controls (p = 0.045). A strong association between POI and increased TGAb (adjusted odds ratio 3.586, p = 0.028), increased TPOAb (adjusted odds ratio 7.496, p = 0.003) and any increased autoimmune parameter (adjusted odds ratio 3.189, p = 0.008) could be demonstrated in a binary logistic regression model. A high prevalence of autoimmunity in POI women compared to a healthy young collective could be demonstrated. Thyroid antibodies were significantly increased in POI women. Our data highlight the increased risk for autoimmune diseases, especially for thyroid disorders. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are characterized by a breakdown of immune tolerance, leading to inflammation and irreversible end-organ tissue damage. Platelet extracellular vesicles are cellular elements that are important in blood circulation and actively participate in inflammatory and immune responses through intercellular communication and interactions between inflammatory cells, immune cells, and their secreted factors. Therefore, platelet extracellular vesicles are the "accelerator" in the pathological process of autoimmune diseases; however, this robust set of functions of platelet extracellular vesicles has also prompted new advances in therapeutic strategies for autoimmune diseases. In this review, we update fundamental mechanisms based on platelet extracellular vesicles communication function in autoimmune diseases. We also focus on the potential role of platelet extracellular vesicles for the treatment of autoimmune diseases. Some recent studies have found that antiplatelet aggregation drugs, specific biological agents can reduce the release of platelet extracellular vesicles. Platelet extracellular vesicles can also serve as vehicles to deliver drugs to targeted cells. It seems that we can try to silence or inhibit microRNA carried by platelet extracellular vesicles transcription and regulate the target cells to treat autoimmune diseases as platelet extracellular vesicles can transfer microRNA to other cells to regulate immune-inflammatory responses. Hopefully, the information presented here will provide hope for patients with autoimmune diseases. Autoimmune diseases patients are characterized by autoimmune disorders, whose immune system cannot distinguish between auto- and foreign-antigens. Autoimmune diseases is the third significant disease threatening human health after cardiovascular disease and cancer. However, the exact etiology of autoimmune diseases has yet to be fully elucidated. Several studies have shown that platelet extracellular vesicle content is elevated in multiple autoimmune disorders and positively correlates with disease activity. However, our knowledge about the details of the mechanisms still remains limited and fragmentary. This article updates the communication function of platelet extracellular vesicles in accelerating autoimmune and inflammatory responses. The interesting thing is every coin has two sides. We put forward a new treatment idea for AD based on the particular volume and powerful intercellular communication function of platelet extracellular vesicles. Inhibition of the communication function of platelet extracellular vesicles seems to be considered in the future, or silence or block miRNA of platelet extracellular vesicles involved in the pathogenesis of AD. We can even use it as a drug carrier to deliver the drug to the relevant target cells, thereby enhancing the role of the medicine in regulating immune response and inhibiting inflammation. This paper not only provides a deeper understanding of the pathogenesis of autoimmune diseases but also provides theoretical support for the use of platelet extracellular vesicles to achieve targeted therapy. [ABSTRACT FROM AUTHOR]

Autoimmune diseases disproportionately affect women and have been linked to increased risk of maternal and perinatal mortality and morbidity. Our aim was to determine the prevalence of autoimmune disease among pregnant women and women of reproductive age (WRA), which is not well described. A population-based study was conducted using data from a survey of general practitioner (GP) encounters and state-wide hospital admissions in New South Wales (NSW). A list of 29 conditions and relevant diagnosis codes was used to identify autoimmune disease. Prevalence estimates and trends were calculated using population denominators for GP encounters for WRA in 2011–2015 and hospital admissions for WRA and pregnant women in 2013–2017. A total 31,065 GP encounters for WRA were identified and 607 (2.0%) reported an autoimmune disease, equivalent to 1.1 GP encounters per 10 WRA each year when extrapolating to NSW population figures. For WRA admitted to hospital, 2.6% had an autoimmune diagnosis recorded each year equivalent to a population prevalence of 0.5%. A total 477,243 births were identified, of which 4230 mothers (0.9%) had at least one autoimmune disease recorded during a 1-year pregnancy lookback period. Autoimmune disease prevalence among both pregnant women and WRA either attending GP or hospital increased, on average, 2–4% per year over the study period. A small, but potentially growing proportion of reproductive age and pregnant women have a diagnosed autoimmune disease, and this may impact their health outcomes. [ABSTRACT FROM AUTHOR]

This article explores the psychical expression of autoimmunity in the analytic situation; it is informed by biological theories of autoimmunity in contemporary immunology. Several of my patients developed autoimmune conditions in the course of their analyses, leading me to consider the role of psychical change in disrupting one's somatopsychic equilibrium. In the psychoanalytic literature, autoimmunity is used metaphorically for attack against what is foreign or unwanted in ourselves. Contemporary immunology, however, suggests a somewhat different metaphor. "Self-reactive" cells present in the body may attack self unless suppressed by inhibitory mechanisms. Biologically, limited self-destructiveness is necessary, but in autoimmune disease it becomes excessive and pathological. I suggest that the presence of biological "self-reactivity" implies an inherent self-destructiveness in line with Freud's thinking on the death instinct; the notion that this self-destructiveness also has adaptive aspects may contribute to our understanding of Freud's ideas. In three vignettes I illustrate clinical application of a modified metaphor of autoimmunity, finding that not only is the fusion of life and death instincts important for psychic development, but so is defusion when contained within the analytic relationship. The analytic task is to restore the balance between constructive and pathological self-destructiveness. Implications regarding controversies in psychosomatic theory are briefly considered. [ABSTRACT FROM AUTHOR]

Miller Fisher syndrome (MFS) is a rare variant of Guillain–Barré syndrome that is characterised by ataxia, ophthalmoplegia, and areflexia. Its relation with other autoimmune diseases is scarcely found in the literature, and in those few cases, treatment has been especially difficult. We report a case of a 28-year-old woman who presented with ophthalmoplegia and ptosis, later developing facial palsy and hyporeflexia. She had positive GD1a, GT1a, GQ1b antibodies confirming MFS. She also had positive antinuclear and lupus anticoagulant antibodies confirming antiphospholipid syndrome. She had a mild clinical course. MFS can present with multiple autoimmunity; it is unclear if there is cross-reactivity due to myelin damage. [ABSTRACT FROM AUTHOR]

Protein kinase C is a family of serine/threonine kinases that play a key role in the adaptive immune cell signaling, as well as regulation of growth, apoptosis, and differentiation of a variety of cell types. Patients homozygous for a null mutation of the Protein Kinase C Delta (PRKCD) gene, present clinical feature of immune dysregulation with susceptibility to Epstein-Barr virus infection. However, a minority of patients present the autoimmune lymphoproliferative syndrome (ALPS). The data were collected by direct interview and examining the patient's clinical record. Whole-exome sequencing was performed to detect the underlying genetic mutation in the patient. We also conducted electronic searches for ALPS-like reported patients in PubMed, Web of Science, and Scopus databases. In this study, we reported a 13-year-old boy who presented with autoimmunity, lymphoproliferation, recurrent pneumonia, cardiomyopathy, and dermatological manifestations. An elevation of double-negative T cells, CD8+ T cells, serum IgG level, as well as a reduction in NK cells, was observed in the patient. A homozygous frameshift mutation (c.1293_1294insA) in exon 13 of the PRKCD gene was confirmed. The literature search showed 39 ALPS-like patients with monogenic defects which only six (15.3%) of them were due to PRKCD genes. PRKCD should be considered in the context of ALPS clinical manifestations with prominent dermatological involvements. [ABSTRACT FROM AUTHOR]

Rheumatic fever (RF) and its sequel rheumatic heart disease (RHD) is an autoimmune disease caused by an abnormal host immune response to group A streptococcus (GAS) infection. The HLA class II molecules are entailed in immune-mediated infectious, inflammatory, and autoimmune diseases including RHD. However, HLA class II genes are reported to be associated with RF/RHD across different populations with a very little consistency. The aim of the study is to investigate the association between HLA class II genes and RF/RHD by meta-analysis. A comprehensive literature search was conducted to identify all relevant case-control studies published before December 31, 2019. The data were extracted using standardized form and pooled odds ratio (OR) with 95% confidence interval (CI) are calculated to assess the strength of the association between HLA class II genes and RF/RHD. Thirteen studies for HLA-DRB1 alleles (1065 patients and 1691 controls) and eight studies for HLA-DQB1 alleles (644 patients and 1088 controls) were finally included. The meta-analysis showed a significantly higher frequency of HLA-DRB1*07 allele (OR = 1.68, P <.0001) in RF/RHD patients when compared to controls, while the frequency of HLA-DRB1*15 allele (OR = 0.60, P =.03) was significantly lower in RF/RHD patients than in controls. However, there were no significant differences in the frequency of HLA-DQB1 alleles between RF/RHD patients and controls. The results of the meta-analysis suggest that the differential presentation of autoimmune peptides by HLA-DRB1*07 (susceptible) and HLA-DRB1*15 (protective) alleles with different affinities may play a crucial role in the pathogenesis of RF/RHD. [ABSTRACT FROM AUTHOR]

This study was performed to compare the prevalence of autoimmune thyroid disease (AITD) assessed by thyroid peroxidase antibody (anti-TPO Ab) and thyroid ultrasonography (USG) in Korean women with polycystic ovary syndrome (PCOS) (n = 210) and age-matched controls (n =343). We also compared the clinical features of women with PCOS according to the presence of AITD. Patients and controls were enrolled from a population who visited a screening centre for a general health check-up. There was no difference in the frequency of anti-TPO Ab positivity between the women with PCOS and the controls (4.8% (5/104) in patients and 7.6% (18/238) in controls). The frequency of heterogeneous or hypoechoic parenchyma on USG also did not differ between the patients and controls (9.3% (11/118) in patients and 12.3% (40/325) in controls). Within the PCOS group, the subjects with AITD (who had either Ab positivity or sonographic findings compatible with thyroiditis) showed significantly higher body mass indexes, waist circumferences and homeostasis model assessment for insulin resistance levels than the patients without AITD. In conclusion, AITD was not more prevalent in women with PCOS than in controls. However, among women with PCOS, subjects with AITD showed significantly higher adiposity and insulin resistance index than those without AITD. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL6) is involved in pathogenesis of several autoimmune disorders including vitiligo. Hence, we aimed to investigate the association of IL6 −174 G/C and −572 G/C polymorphisms and its transcript levels with vitiligo; to evaluate the effect of IL-6 on normal human melanocyte (NHM) viability and expression of IL6R, MITF and TYR. IL6 -174 G/C and −572 G/C polymorphisms were genotyped by ARMS-PCR and PCR-RFLP respectively in 343 controls and 322 vitiligo patients. IL6 transcript levels were estimated from PBMCs (96 controls and 77 patients) and skin samples (15 controls and 15 patients) by qPCR. NHM viability was assessed by MTT; IL6R, MITF and TYR transcript and protein levels were monitored by qPCR and ICC respectively. Genetic analyses revealed no association of IL6 −174 G/C polymorphism (p>.05) with vitiligo. Analysis of IL6 −572 G/C revealed reduced risk of vitiligo in individuals with GC/CC genotypes compared to GG genotype (p =.010). IL6 expression was significantly increased (p =.0197) in PBMCs of patients. Further, IL6 expression was significantly higher in non-lesional skin compared to controls (p =.009). In-vitro NHM viability was decreased upon IL-6 exposure (10-50 ng/ml; p<.05), with significantly increased IL6R transcript (p =.042) and protein levels (p =.003) however, MITF transcript (p =.0003) and protein levels (p =.016), and TYR transcript levels (p =.001) were significantly decreased. The results suggest that IL6 −572 G/C polymorphism might be associated with vitiligo susceptibility in Gujarat population. Moreover, increased IL6 expression in vitiligo patients and its effect on NHM suggest a potential role in melanocyte biology. The results suggest that IL6 − 572 G/C polymorphism might be associated with vitiligo susceptibility in Gujarat population. Moreover, increased IL6 expression in vitiligo patients and its effect on NHM suggest a potential role in melanocyte biology. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is the most common immune-mediated CNS disease, characterised by demyelination and progressive neurological disability. The B-cell activating factor BAFF has been described as one important factor in the pathophysiology of different autoimmune diseases. We measured BAFF levels in the serum and cerebrospinal fluid (CSF) in 50 consecutive patients with MS and 35 patients with infectious CNS disease (ID). 52 patients with other, non-inflammatory disorders (OND), served as controls. BAFF-serum levels in ID patients were higher than in patients diagnosed with MS (ID 0.55 ± 0.24 ng/ml, MS 0.43 ± 0.14 ng/ml, OND 0.45 ± 0.24 ng/ml; p = 0.09). Interestingly, MS patients had lower BAFF CSF levels compared to the controls and ID patients, and the CSF levels in the latter were elevated compared to those of the controls (MS 0.17 ± 0.11 ng/ml, OND 0.25 ± 0.14 ng/ml, ID 0.97 ± 0.78 ng/ml; p < 0.001). The ID patients' having higher absolute BAFF levels in the CSF than in the serum indicates that the increased BAFF CSF levels were caused by intrathecal synthesis rather than passive transfer via a disturbed blood-brain-barrier. The significantly decreased BAFF CSF levels in MS patients were a surprising result of our study. Although it has been reported that astrocytes in active MS lesions can express BAFF, the soluble form was not increased in the CSF of MS patients. It remains unclear whether the inflammatory features of active MS plaques are truly represented by the CSF compartment. [ABSTRACT FROM AUTHOR]

As COVID-19 is a new emerging disease, the hematological/immunological changes that develop in the infected patients remain unknown. This study aims to systematically review the hematologic autoimmune complications in these patients. Data from three online databases including Medline (via PubMed), Scopus and Web of Science were searched on 19 December 2020, and after excluding duplicate, irrelevant and inappropriate records, eligible documents were identified. Afterwards, information such as patients' history, presentations, paraclinical data, treatment course and outcome were extracted from the records. A total of 58 documents were considered to be eligible for data extraction which described 94 patients with COVID-19 who developed hematologic autoimmune disorder in their course of infection. Of these patients with COVID-19, the most common hematologic autoimmune disorder was immune thrombocytopenic purpura (55 cases) followed by autoimmune hemolytic anemia (22 cases). Other hematologic autoimmune disorders include antiphospholipid syndrome, thrombotic thrombocytopenic purpura, Evans syndrome and autoimmune neutropenia. The current study would help us to always consider an autoimmune etiology for cases with abnormal hematologic finding which further lead to an appropriate treatment of the patients, especially when the symptoms present in about 1–2 weeks after the first manifestation of the infection symptoms. Maybe, at least in this pandemic, it should be recommended to evaluate patients with unexpected and unexplained decrease in their hemoglobulin or platelet count for COVID-19. Another challenging issue is the treatment options. Given the multiorgan involvement and multifaceted nature of the infection, an individualized approach should be taken for each patient. [ABSTRACT FROM AUTHOR]

Ectopic lymphoid structures (ELS) or tertiary lymphoid organs are structures with the organization similar to the one of secondary lymphoid organs, formed in non-lymphoid tissues. They are considered to be an important site for the lymphocytic physiological and pathological role in conditions such are chronic infections, autoimmune diseases, cancer, and allograft rejection. Although similar to the secondary lymphoid tissues, the initiation of ELS formation is not preprogramed and requires chronic inflammation, expression of homeostatic chemokines, and lymphotoxin beta receptor activation. Importantly, while ELS formation may be considered beneficiary in antimicrobial and antitumor immunity, the persistence of these active lymphoid structures within the tissue increase the chance for development of autoimmunity and lymphoma. This paper is providing an overview of biological mechanisms involved in ELS formation, as well as the overview of the pathophysiological role of these structures. In addition, the paper discusses the possibility to therapeutically target ELS formation, bearing in mind their bivalent nature and role in different pathophysiological conditions. [ABSTRACT FROM AUTHOR]

In addition to generating effective immunity against infectious agents, the immune system helps to fight against different noninfectious human diseases while maintaining the balance between self and non-self discrimination. The breakdown of tolerance in autoimmune diseases or sustainable tolerance in an abnormal microenvironment such as chronic inflammation may initiate the process of malignancy. Immune system regulation is controlled by a complex, dynamic network of cells and mediators. Understanding the cellular and molecular basis of immune regulation provides better insight into the mechanisms governing the immune pathology of diseases. Among several cellular subsets and mediators with regulatory roles, a subpopulation of CD4+ T cells was recently reported to be positive for FoxP3 and negative for CD25, with a suggested range of functional activities in both cancer and autoimmune diseases. This CD4 subset was first reported in 2006 and thought to have a role in the pathogenesis of cancer. However, the spectrum of roles played by this T cell subset is broad, and no consensus has been reached regarding its immunological functions. In this review, we focused on the possible origin of CD4+CD25‒FoxP3+ T cells and their function in cancer and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Chronic inflammation drives proliferative responses, hence increasing cellular multiplication with the consequent risk of malignant transformation. Autoimmune responses against self-antigens drive chronic inflammation but may also enhance cancer immunosurveillance with the consequent reduction of tumor incidence and progression. These notions, which have been well established at the preclinical level, may explain the generally positive associations between immune-inflammatory diseases but also some negative associations, for example between breast cancer and rheumatoid arthritis or systemic lupus erythematosus, which have recently been confirmed in a study enrolling close to half a million participants from the UK Biobank. [ABSTRACT FROM AUTHOR]