Molecular mimicry in multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection1,2, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein. The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity. Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases.

Pathologic Analysis of Twenty-one Appendices From Children With Multisystem Inflammatory Syndrome Compared to Specimens of Acute Appendicitis: A Cross-sectional Study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of coronavirus disease 2019, commonly involving the gastrointestinal tract. Some children with MIS-C undergo appendectomy before the final diagnosis. There are several hypotheses explaining the pathomechanism of MIS-C, including the central role of the viral antigen persistence in the gut, associated with lymphocyte exhaustion. We aimed to examine appendectomy specimens from MIS-C patients and assess their pathologic features, as well as the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens. METHODS: In this cross-sectional study we included 21 children with MIS-C who underwent appendectomy. The control group included 21 sex- and age-matched children with acute appendicitis (AA) unrelated to SARS-CoV-2 infection. Histologic evaluation of appendiceal specimens included hematoxylin and eosin staining and immunohistochemical identification of lymphocyte subpopulations, programmed cell death protein-1 (PD-1) and SARS-CoV-2 nucleocapsid antigen. RESULTS: Appendices of MIS-C patients lacked neutrophilic infiltrate of muscularis propria typical for AA (14% vs. 95%, P < 0.001). The proportion of CD20+ to CD5+ cells was higher in patients with MIS-C (P = 0.04), as was the proportion of CD4+ to CD8+ (P < 0.001). We found no proof of SARS-CoV-2 antigen presence, nor lymphocyte exhaustion, in the appendices of MIS-C patients. CONCLUSIONS: The appendiceal muscularis of patients with MIS-C lack edema and neutrophilic infiltration typical for AA. SARS-CoV-2 antigens and PD-1 are absent in the appendices of children with MIS-C. These findings argue against the central role of SARS-CoV-2 persistence in the gut and lymphocyte exhaustion as the major triggers of MIS-C.

Protective mechanisms of Leontopodium leontopodioides extracts on lipopolysaccharide-induced acute kidney injury viathe NF-κB/NLRP3 pathway / 中国天然药物

Sepsis-induced uncontrolled systemic inflammatory response syndrome (SIRS) is a critical cause of multiple organ failure. Acute kidney injury (AKI) is one of the most serious complications associated with an extremely high mortality rate in SIRS, and it lacked simple, safe, and effective treatment strategies. Leontopodium leontopodioides (Willd.) Beauv (LLB) is commonly used in traditional Chinese medicine for the treatment of acute and chronic nephritis. However, it remains unclear whether lipopolysaccharide (LPS) affects LPS-induced AKI. To identify the molecular mechanisms of LLB in LPS-induced HK-2 cells and mice, LLB was prepared by extraction with 70% methanol, while a lipopolysaccharide (LPS)-induced HK-2 cell model and an AKI model were established in this study. Renal histopathology staining was performed to observe the morphology changes. The cell supernatant and kidney tissues were collected for determining the levels of inflammatory factors and protein expression by ELISA, immunofluorescence, and Western blot. The results indicated that LLB significantly reduced the expression of IL-6 and TNF-α in LPS-induced HK-2 cells, as well as the secretion of IL-6, TNF-α, and IL-1β in the supernatant. The same results were observed in LPS-induced AKI serum. Further studies revealed that LLB remarkably improved oxidative stress and apoptosis based on the content of MDA, SOD, and CAT in serum and TUNEL staining results. Notably, LLB significantly reduced the mortality due to LPS infection. Renal histopathology staining results supported these results. Furthermore, immunofluorescence and Western blot results confirmed that LLB significantly reduced the expression of the protein related to the NF-κB signaling pathway and NLRP3, ASC, and Caspase-1 which were significantly increased through LPS stimulation. These findings clearly demonstrated the potential use of LLB in the treatment of AKI and the crucial role of the NF-κB/NLRP3 pathway in the process through which LLB attenuates AKI induced by LPS.

Una causa infrecuente de síndrome inflamatorio sistémico / A rare cause of systemic inflammatory response syndrome

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Enfermedad relacionada con IgG4 / IgG4-related disease

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Evaluation of systemic inflammatory responses in cholecystectomy by means of access. Single-port umbilical incision, transvaginal NOTES, laparoscopy and laparotomy

PURPOSE: To evaluate and compare clinical and inflammatory responses to the surgical trauma caused by cholecystectomy via several access approaches: single-port umbilical incision (SILS), transvaginal natural orifice transluminal endoscopic surgery (NOTES), laparoscopy, and Laparotomy.METHODS: Twenty-eight female pigs were equally divided into four groups and submitted to cholecystectomy by single-port umbilical incision, transvaginal NOTES, laparoscopy, or Laparotomy. An additional five animals served as controls (sham group). Animals were monitored perioperatively regarding anesthesia and surgical procedure times, as well as for the presence of complications. Postoperatively, they were evaluated regarding time to ambulation and feeding, and the presence of clinical events. Procalcitonin, C-reactive protein (CRP), and AQUI feron-gamma (IFN-γ) measurements were performed before surgery and immediately, two days, and seven days after surgery. Animals were sacrificed and necropsied at seven days after surgery.RESULTS: All procedures were successfully performed as proposed in each group. Only minor complications, such as gallbladder perforation and bleeding from the liver bed, were observed during surgery in all groups. The vaginal NOTES group showed higher anesthesia and surgical procedure times compared to the other groups (p<0.001). No other between-group differences in perioperative or postoperative times, clinical evolution, or serum inflammatory markers were observed. Only adhesions were found on necropsy, with no differences between groups.CONCLUSION: The single-port umbilical and transvaginal NOTES access approaches were feasible and safe compared to laparoscopic and laparotomy for cholecystectomy.

Bases morfofisiopatológicas de la respuesta inflamatoria aguda pulpar / Morphophysiopathological bases of pulpar acute inflammatory response

Teniendo en cuenta el desconocimiento existente sobre las bases morfofisiopatológicas que caracterizan la respuesta inflamatoria aguda pulpar; conocimiento este que resulta imprescindible para tomar decisiones según se trate de enfermedades pulpares reversibles o irreversibles, tratables o intratables, tejidos para el recubrimiento y su conservación o pulpas que deben ser extraídas, se decidió describir las mencionadas bases en el presente artículo, con la finalidad de que se reflexione acerca de ello y se debatan los aspectos de mayor interés en relación con el tema.

Given the lack of knowledge on morphophysiopathological bases characterizing pulpar acute inflammatory response, which becomes essential knowledge to make decisions depending on reversible or irreversible and treatable or untreatable pulpar diseases, tissues for covering and preservation or pulps to be extracted, it was decided to describe the bases mentioned in this article in order to reflect on this and to discuss the aspects of greatest significance in relation to the topic.

Apresentação grave de Doença de Still do adulto / Severe Still disease in adults

Doença de Still do Adulto (DAS), uma variante da artrite reumatóide juvenil, é uma síndrome caracterizada por artralgia, febre elevada, rash cutâneo, linfadenomegalia e hepatoesplenomegalia. O diagnóstico é de exclusão baseado em critérios estudados. O diagnóstico diferencial inclui infecções, malignidades e doenças imunológicas. O curso da doença varia entre formas leves e bem agressivas, havendo relatos de alguns casos de DSA evoluindo com choque. Paciente branca, feminina, quarenta e nove anos procura o hospital com queixa de febre, náusea e mialgia há três semanas com indisposição, artrite simétrica de mãos e febre com calafrios. Identificada esplenomegalia no exame físico e linfonodomegalia cervical posterior esquerda. Em três dias, apresentou hipotensão grave, insuficiência renal aguda (IRA), coagulação intravascular disseminada (CIVD) e acidose metabólica, preenchendo critérios para sepse grave e disfunção de múltiplos órgãos e sistemas (DMOS), sendo tratada com volume, drogas vasoativas, glicocorticóide em altas doses e proteína C ativada (drotrecogina). Foram iniciados cefepime e vancomicina empiricamente. Em uma semana, após melhora inicial, a paciente desenvolveu nova piora clínica. Prostração, febre, tosse seca e eritema, desta vez associados a petéquias em membros inferiores e leucopenia (1590 leucócitos, sendo 650 neutrófilos) surgiram e, como já havia dez dias de cefepime e vancomicina, foi iniciado novo esquema empírico para sepse hospitalar de origem desconhecida com meropenem e fluconazol. Glicocorticóide foi reinstituído como parte da abordagem de choque séptico e foi repetida a ecografia abdominal que não mostrou alterações evolutivas. Com base em vasto rastreamento infeccioso negativo, decidiu-se pela terapia imunossupressora com doses elevadas de glicocorticóide, sem suspensão dos antibióticos, sendo seu desfecho favorável. Apenas alguns casos de choque distributivo foram descritos no contexto de DSA e este seria o primeiro relato de um...