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Unexpected anti-red blood cell (RBC) alloantibodies are routinely investigated in immunohematology and blood banking since their existence in pregnant women may induce haemolytic disease of the foetus and newborn, and their presence in donors may induce haemolytic transfusion reactions or hyperacute rejection in solid organ transplantation. Unexpected anti-RBC alloantibodies may target antigens of the most blood types excluding the expected antibodies targeting the ABO antigens. Their incidence in humans was originally linked to alloimmunization events such as blood transfusions, transplants, or pregnancies. But later, many findings revealed their existence in pathogenic processes such as malignancies, infections, and autoimmune diseases; and usually (but not always) associated to autoimmune haemolytic anaemia (AIHA). Nevertheless, unexpected anti-RBC autoantibodies are also occasionally found in healthy individuals in the absence of AIHA and with no history of alloimmunization or the associated pathologic processes. Hence, they are generally known as non-clinically significant, are excluded for typification and called "silent red blood cell autoantibodies (SRBCAA)". This review highlights evidence related to genetic predisposition, molecular mimicry, immune dysregulation, and immune tolerance loss surrounding the existence of anti-RBC antibodies, describing the presence of SRBCAA as possible early witnesses of the development of autoimmune diseases.

Introduction The main cause of cervical cancer is an infection of keratinocytes in the basal layer of the stratified epithelium of the cervix by human papillomavirus (HPV). Other than in cervical samples, HPV DNA has been found in serum and other fluids but its origin is unclear. Extracellular vesicles (EV) could be a conveyance of viral DNA given their emerging role in cellular communication. The content of EV derived from cervical cells has not been properly explored and it is not known whether or not they contain HPV DNA. Methods We evaluated the DNA content of exosomes purified from cultures of HeLa cells by Next Generation Sequencing (NGS) and confirmed its presence by PCR. The presence of HPV DNA was also evaluated by PCR and NGS in EV from HPV-positive cervical samples without apparent lesion or with LSIL. Results We detected the integrated form of viral-DNA in exosomes from HeLa cells by NGS and confirmed its presence by PCR. The search for HPV sequences in EV obtained from cervical exudate samples without apparent lesion or with LSIL, where we expected to find the viral genome as an episome, indicated that HPV DNA, including the E6 and E7 oncogenes, is present in these EV. Conclusion HPV DNA, including the viral oncogenes E6/E7, is found in exosomes regardless of the integration status of the virus in the infected cell.

Neutrophil extracellular traps (NETs) are networks of decondensed chromatin loaded with antimicrobial peptides and enzymes produced against microorganisms or biochemical stimuli. Since their discovery, numerous studies made separately have revealed multiple triggers that induce similar NET morphologies allowing to classify them as lytic or non-lytic. However, the variability in NET composition depending on the inducer agent and the local milieu under similar conditions has been scarcely studied. In this work, a comparative study was conducted to evaluate structural and enzymatic divergences in NET composition induced by biochemical (phorbol myristate acetate [PMA] and hypochlorous acid [HOCl]) and microbiologic (Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa) stimuli, along with the presence of plasma from healthy donors or patients with systemic lupus erythematosus (SLE). The results showed a differential composition of DNA and the antimicrobial peptide cathelicidin (LL37) and a variable enzymatic activity (neutrophil elastase, cathepsin G, myeloperoxidase) induced by the different stimuli despite showing morphologically similar NETs. Additionally, SLE plasma´s presence increased DNA and LL37 release during NET induction independently of the trigger stimulus but with no enzymatic activity differences. This work provides new evidence about NET composition variability depending on the inducer stimulus and the local milieu.

Demodex folliculorum shows a high occurrence in the general population, however, its pathologic relevance is still controversial. In this prospective study, we evaluated the prevalence of D. folliculorum on eyelashes from 8,033 subjects of a university population (including 7,782 students, and 251 academics). Additional information on some risk factors to infection by the mites was evaluated, as well. A prevalence of 1.47% was found, where 118 individuals were positive for D. folliculorum; and, among them, 63 (53.4%) were women and 55 (46.6%) were men. Results showed a negative correlation with the age (r = −0.45), the highest prevalence was found in individuals between 19 and 22 years of age (2.1%, 84 patients). The number of D. folliculorum mites did not differ between the right and left eye; however, the use of cosmetics or facial cream, contact lens, hair removers, were factors present in patients infected with D. folliculorum. Although Demodex prevalence did not increase in line with weight, we found significantly higher prevalence in the 51–60 kg and 71–80 kg weight groups, and a particularly high prevalence in the over 81 kg weight group (2.6%). In conclusion, it was observed that the main population positive to infection consisted of young adults; this is in contrast with the international evidence reporting a high rate of infection in older adults. Besides, our results suggest that items of daily use such as cosmetics, facial cream, eyeliner, glasses, or contact lenses may be some of the main culprits of the infection by D. folliculorum.

Pulmonary fibrosis is an emerging disease with a poor prognosis and high mortality rate that is even surpassing some types of cancer. This disease has been linked to the concomitant appearance of liver cirrhosis. Bleomycin-induced pulmonary fibrosis is a widely used mouse model that mimics the histopathological and biochemical features of human systemic sclerosis, an autoimmune disease that is associated with inflammation and expressed in several corporal systems as fibrosis or other alterations. To determine the effects on proliferation, redox and inflammation protein expression markers were analyzed by immunohistochemistry. Analyses showed a significant increase in protein oxidation levels by lipoperoxidation bio-products and in proliferation and inflammation processes. These phenomena were associated with the induction of the redox status in mice subjected to 100 U/kg bleomycin. These findings clearly show that the bleomycin model induces histopathological alterations in the liver and partially reproduces the complexity of systemic sclerosis. Our results using the bleomycin-induced pulmonary fibrosis model provide a protocol to investigate the mechanism underlying the molecular alteration found in the liver linked to systemic sclerosis.

Since their description, extracellular vesicles (EVs) have shown growing relevance in cancer progression. These cell structures contain and transfer molecules such as nucleic acids (including DNA and RNA), proteins, and lipids. Despite the rising information about EVs’ relationship with cancer, there is still scarce evidence about their content and function in cervical cancer. Interestingly, the composition and purposes of some cellular molecules and the expression of oncogenic proteins packaged in EVs seem modified in HPV-infected cells; and, although only the E6 oncogenic protein has been detected in exosomes from HPV-positive cells, both E6/E7 oncogenes mRNA has been identified in EVs; however, their role still needs to be clarified. Given that EVs internalizing into adjacent or distant cells could modify their cellular behavior or promote cancer-associated events like apoptosis, proliferation, migration, or angiogenesis in receptor cells, their comprehensive study will reveal EV-associated mechanisms in cervical cancer. This review summarizes the current knowledge in composition and functions of cervical cancer and HPV Infection-derived EVs.

Irregular antibodies are produced by alloimmunization because of pregnancies or blood transfusions. They are called “irregular” due to target erythrocyte antigens from “rare blood systems,” those different from the ABO system. Irregular antibodies have been widely investigated in immunohematology since their presence in blood donors may lead to difficulties in blood typing and in blood cross-matching, or to induce hemolytic transfusion reactions. Nevertheless, their incidence and participation in the physiopathology of autoimmune diseases have not been thoroughly studied. In this work, we analyzed the presence and pro-hemolytic capabilities of irregular antibodies in patients with different autoimmune diseases lacking signs of hemolytic anemia, in comparison with healthy multiparous women. Five of 141 autoimmune patients (3.5 %) and two of 77 multiparous women (2.6 %) were positive. Although frequency was relatively low and similar in both populations, the targeted antigens were Kell (k, Kpb, Jsb) and Luth (Lub) in multiparous women, and the same plus Duffy (Fya), Kidd (Jka) and MNS (M, s) in autoimmune patients. Irregular antibodies from autoimmune patients did not induce complement-mediated hemolysis (intravascular), but they were able to induce macrophages-mediated phagocytosis (extravascular hemolysis) in vitro. It is the first approach exploring the presence of irregular antibodies associated with the loss of immune tolerance and demonstrating their hemolytic potential in autoimmune patients without hemolytic manifestations. The presence of irregular antibodies targeted to Duffy (Fya), Kidd (Jka) and MNS (M, s) antigens only in autoimmune patients suggests a loss of immune tolerance to these erythrocyte antigens.