Deciphering the Contribution of BP230 Autoantibodies in Bullous Pemphigoid.

Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease predominantly affecting elderly patients and carries significant morbidity and mortality. Patients typically suffer from severe itch with eczematous lesions, urticarial plaques, and/or tense blisters. BP is characterized by the presence of circulating autoantibodies against two components of the hemidesmosome, BP180 and BP230. The transmembrane BP180, also known as type XVII collagen or BPAG2, represents the primary pathogenic autoantigen in BP, whereas the intracellular BP230 autoantigen is thought to play a minor role in disease pathogenesis. Although experimental data exist suggesting that anti-BP230 antibodies are secondarily formed following initial tissue damage mediated by antibodies targeting extracellular antigenic regions of BP180, there is emerging evidence that anti-BP230 IgG autoantibodies alone directly contribute to tissue damage. It has been further claimed that a subset of patients has a milder variant of BP driven solely by anti-BP230 autoantibodies. Furthermore, the presence of anti-BP230 autoantibodies might correlate with distinct clinical features. This review summarizes the current understanding of the role of BP230 and anti-BP230 antibodies in BP pathogenesis

Insights Into the Pathogenesis of Bullous Pemphigoid: The Role of Complement-Independent Mechanisms.

Bullous pemphigoid is an autoimmune blistering disease caused by autoantibodies targeting BP180 and BP230. While deposits of IgG and/or complement along the epidermal basement membrane are typically seen suggesting complement -mediated pathogenesis, several recent lines of evidence point towards complement-independent pathways contributing to tissue damage and subepidermal blister formation. Notable pathways include macropinocytosis of IgG-BP180 complexes resulting in depletion of cellular BP180, direct induction of pro-inflammatory cytokines from keratinocytes, as well as IgE autoantibody- and eosinophil-mediated effects. We review these mechanisms which open new perspectives on novel targeted treatment modalities

Assessing the prevalence of autoimmune, endocrine, gynecologic, and psychiatric comorbidities in an ethnically diverse cohort of female fibromyalgia patients: does the time from hysterectomy provide a clue?

Background: This retrospective chart review investigated differences in the prevalence of medical comorbidity between women with fibromyalgia (FM) (n=219) and a control group women with chronic pain (CP) without FM (n=116). The specific aims were to compare the prevalence of autoimmune, psychiatric, endocrine, gynecologic pathology, the relationship between timing of gynecologic surgery, and pain onset. We additionally sought to compare the number of comorbidities in an ethnically diverse cohort. Methods: This was a retrospective chart review of patients seen in FM or CP clinics at an academic medical center in 2009–2010. Results: Logistic regression modeling found that gynecologic, endocrine, and autoimmune diagnoses were independently associated with a diagnosis of FM. Detailed analyses showed that thyroid disease (P\u3c0.01) and gynecologic surgery (P\u3c0.05) were significantly more common in FM. Women with FM were more likely to have multiple autoimmune, endocrine, gynecologic, or psychiatric pathologies. A relationship was observed between the timing of gynecologic surgery and pain onset in FM, with more surgeries observed in the years just prior to pain onset or in the year after pain onset. A similar pattern was not found in the control group. Conclusion: This study demonstrates that autoimmune, endocrine, and gynecologic pathologies occur more commonly in women with FM than in those with CP, which is consistent with findings in less ethnically diverse samples. Moreover, a relationship was found between timing of pain onset and gynecologic surgery. A larger prospective study of the relationship between gynecologic surgery and pain onset in FM is warranted

Penghidap SMA cemerlang akademik

Saya hanya boleh menulis dan memegang beban tidak melebihi 500gram. Lebih daripada itu memang saya tidak mampu," kata Siti Hawa Apandi, 24, dari Taman Mahkota Aman, di sini

Inverse dynamic modelling of jumping in the red-legged running frog, Kassina maculata

Although the red-legged running frog, Kassina maculata, is secondarily a walker/runner, it retains the capacity for multiple locomotor modes, including jumping at a wide range of angles (nearly 70 deg). Using simultaneous hind limb kinematics and single-foot ground reaction forces, we performed inverse dynamics analyses to calculate moment arms and torques about the hind limb joints during jumping at different angles in K. maculata. We show that forward thrust is generated primarily at the hip and ankle, while body elevation is primarily driven by the ankle. Steeper jumps are achieved by increased thrust at the hip and ankle and greater downward rotation of the distal limb segments. Because of its proximity to the GRF vector, knee posture appears to be important in controlling torque directions about this joint and, potentially, torque magnitudes at more distal joints. Other factors correlated with higher jump angles include increased body angle in the preparatory phase, faster joint openings and increased joint excursion, higher ventrally directed force, and greater acceleration and velocity. Finally, we demonstrate that jumping performance in K. maculata does not appear to be compromised by presumed adaptation to walking/running. Our results provide new insights into how frogs engage in a wide range of locomotor behaviours and the multi-functionality of anuran limbs

A multi-omic approach identifies an autism spectrum disorder (ASD) regulatory complex of functional epimutations in placentas from children born preterm

Children born preterm are at heightened risk of neurodevelopmental impairments, including Autism Spectrum Disorder (ASD). The placenta is a key regulator of neurodevelopmental processes, though the precise underlying molecular mechanisms remain unclear. Here, we employed a multi-omic approach to identify placental transcriptomic and epigenetic modifications related to ASD diagnosis at age 10, among children born preterm. Working with the extremely low gestational age (ELGAN) cohort, we hypothesized that a pro-inflammatory placental environment would be predictive of ASD diagnosis at age 10. Placental messenger RNA (mRNA) expression, CpG methylation, and microRNA (miRNA) expression were compared among 368 ELGANs (28 children diagnosed with ASD and 340 children without ASD). A total of 111 genes displayed expression levels in the placenta that were associated with ASD. Within these ASD-associated genes is an ASD regulatory complex comprising key genes that predicted ASD case status. Genes with expression that predicted ASD case status included Ewing Sarcoma Breakpoint Region 1 (EWSR1) (OR: 6.57 (95% CI: 2.34, 23.58)) and Bromodomain Adjacent To Zinc Finger Domain 2A (BAZ2A) (OR: 0.12 (95% CI: 0.03, 0.35)). Moreover, of the 111 ASD-associated genes, nine (8.1%) displayed associations with CpG methylation levels, while 14 (12.6%) displayed associations with miRNA expression levels. Among these, LRR Binding FLII Interacting Protein 1 (LRRFIP1) was identified as being under the control of both CpG methylation and miRNAs, displaying an OR of 0.42 (95% CI: 0.17, 0.95). This gene, as well as others identified as having functional epimutations, plays a critical role in immune system regulation and inflammatory response. In summary, a multi-omic approach was used to identify functional epimutations in the placenta that are associated with the development of ASD in children born preterm, highlighting future avenues for intervention