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Immunology of Scleroderma
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Antibodies directed against other proteins have been reported in SSc. Pm-Scl is found in approximately 17% of patients with SSc and identifies a group of SSc patients with a high prevalence of myositis and renal involvement.169 Anti-fibrillin 1 antibodies were detected in the majority of Japanese, African American and Choctaw Indian patients, however, there are ethnic differences in antigenic epitope specificity. The sera from African American patients recognized the N-terminal end of fibrillin 1, whereas in Japanese and Choctaw Indian patients the sera recognized 2 or 3 epitopes. In the few Caucasian patients who had anti-fibrillin 1 antibodies, the EGF-cb repeat and proline-rich C regions were recognized.175 Anti-fibrillarin antibodies occur in patients who develop severe fatal primary arterial hypertension.174,198 Anti-fibrillin antibodies have been identified in a large proportion of patients with other autoimmune diseases including rheumatoid arthritis, SLE and mixed connective tissue diseases.199 Anti-mitochondrial antibodies are found in a high proportion of patients with other connective tissue diseases, however, reactivity to the mitochondrial peptides appears to be disease specific.176 Antibodies to nonhistone nuclear proteins or nucleolar antigens have been described and have been termed Ku, Ro (SS-A), La (SS-B) Sm, nRNP, and Jo-1 have been found in subgroups of patients with SSc.200
Altered Regulation of Fibrinolysis in Scleroderma and Potential for Thrombolytic Therapy
Published in Pia Glas-Greenwalt, Fibrinolysis in Disease Molecular and Hemovascular Aspects of Fibrinolysis, 2019
Marvin J. Fritzler, David A. Hart
The clinical features that distinguish different subsets of scleroderma patients is the subject of investigation by a number of laboratories. In general, patients with extensive cutaneous involvement have arthritis and joint contractures, early visceral involvement, and autoantibodies to topoisomerase I (Scl-70), fibrillarin, or RNA polymerase I (RNA Poll) (reviewed in References 1 and 6). By contrast, limited cutaneous involvement is correlated with calcinosis, telangiectasia, the late development of pulmonary hypertension and primary biliary cirrhosis, and autoantibodies to centromere antigens. Visceral involvement in the absence of skin sclerosis (scleroderma sine scleroderma) is rare. By contrast, Raynaud’s phenomenon is one of the earliest features of the disease and occurs in over 90% of all patients regardless of other clinical features. Since not all patients with Raynaud’s phenomenon develop scleroderma, numerous studies have attempted to identify early predictors of disease progression. Some studies have indicated that up to 40% of patients with Raynaud’s phenomenon go on to develop scleroderma.5,7 In one study, it was concluded that the serum autoantibody detected in the preclinical phase of the disease was the most accurate predictor of outcome.7 Such observations support the concept that certain physiological conditions predispose individuals to develop a slower progression of disease.
Pathogenesis
Published in Aparna Palit, Arun C. Inamadar, Systemic Sclerosis, 2019
Several population-based studies have established the association of ethnicity with development and severity of SSc. The disease occurrence is higher in Choctaw Native Americans and Blacks. There is a younger age of onset, higher frequency of diffuse skin involvement, pulmonary disease, and overall worse prognosis in Black individuals as compared to Whites. The Hispanic and Native Americans develop a more severe disease than Whites. Anti-centromere antibodies are commonly found in Whites, and anti-ribonucleoprotein and anti-fibrillarin antibodies are common in Blacks. Anti-Scl70 antibodies are found in equal frequency in all ethnic groups.5
Multiple pathways of alveolar macrophage death contribute to pulmonary inflammation induced by silica nanoparticles
Published in Nanotoxicology, 2021
Eun-Jung Park, Min-Sung Kang, Seung-Woo Jin, Tae Geol Lee, Gwang-Hee Lee, Dong-Wan Kim, Eun-Woo Lee, Junhee Park, Inhee Choi, Youngmi Kim Pak
Integrity of intracellular organelles. Cells were incubated with 20- or 50-SiNPs at designated concentrations for 24 h. All experiments were performed independently three times according to the manufacturer’s instructions (N = 3). *p < 0.05, **p < 0.01. (A) Volume and membrane potential of mitochondria, (B) Produced total ATP contents, (C) Fluorescence intensity of LysoTracker, (D) Visualization of mitochondria and lysosome. Upper: Labeling of mitochondria (red) and lysosome (green). Lower: Labeling of lysosome (green) with DAPI (blue). Magnification, X 200. (E) ER volume, (F) Released LDH level, (G) Mitochondrial calcium accumulation, (H) Images of the nucleus and cytoskeleton. The nucleus and cytoskeleton were labeled with anti-fibrillarin and anti-β-actin, respectively. Magnification, X 200.
Unfolding the Role of Splicing Factors and RNA Debranching in AID Mediated Antibody Diversification
Published in International Reviews of Immunology, 2021
Ankit Jaiswal, Amit Kumar Singh, Anubhav Tamrakar, Prashant Kodgire
AID was also found physically in the regions of nucleus augmented with splicing factors. To illustrate the localization of AID in the subnuclear structures, high-resolution confocal microscopy was used [70]. Subsequently, it was found that AID was co-localized with fibrillarin in the exportin 1 inhibitor (blocks nuclear export) treated cells [70]. Fibrillarin is a nucleolar protein and is the marker for nucleoli. Similarly, AID and AID1-186 were also co-localized with fibrillarin in the digitonin treated cells. As digitonin is a membrane permeabilizer, if proteins are soluble then it can easily diffuse out of the nucleus and cytoplasm, whereas proteins that are structurally bounded, they cannot diffuse. Thus, AID and AID1-186 are indeed physically associated with nucleoli and subnuclear domain [70].
Comparison of proteomic profiles from the testicular tissue of males with impaired and normal spermatogenesis
Published in Systems Biology in Reproductive Medicine, 2021
Jiaying Liang, Yichun Zheng, Weihong Zeng, Liuqing Chen, Shaofen Yang, Peng Du, Yujiang Wang, Xingsu Yu, Xiqian Zhang
Testicular puncture biopsies were paraffin embedded. To prepare slides, 3-μm paraffin-embedded tissue sections were cut. The slides were deparaffinized, rehydrated, subjected to microwaves for antigen retrieval, and inactivated by endogenous peroxidase. Thereafter, the sections were incubated in 5% bovine serum albumin (BSA) followed by primary antibodies against fibrillarin FBL (sc-166,001; dilution 1:1000; Santa Cruz), YBX1 (20,339-1-AP; dilution 1:500; Proteintech), and HNRNPU antibodies (sc-32,315; dilution 1:500; Santa Cruz) overnight at 4°C. After incubation with horseradish peroxidase-conjugated secondary antibodies, the sections were determined by 3,3′-diaminobenzidine and photographed. Views obtained from five fields of each picture were selected for the quantification of relative protein expression.