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Sadhana Mangwana, Vivek Gangwar
The Kell blood group system is complex, contains many antigens, highly immunogenic, and potent in triggering immune reactions. Antibodies to Kell blood group system are the most common immune red cell antibodies, following ABO and Rh. However, among the anti-Kell antibodies; anti-Kpa is extremely rare. We report an interesting case of Anti-Kpa in a 59-year-old female patient of Non-Hodgkin's Lymphoma, post radiotherapy, who first developed warm autoantibody and later developed anti-Kpa alloantibody on multiple transfusions...
January 2018: Asian Journal of Transfusion Science
Raj Nath Makroo, Saroj Rajput, Soma Agarwal, Mohit Chowdhry, Bindu Prakash, Prashant Karna
BACKGROUND: Alloantibodies may be detected in blood donors who have either been transfused previously or female donors with previous obstetric events. These antibodies can occasionally cause severe transfusion reaction, if a large amount of plasma or whole blood is transfused, as in massive transfusions and pediatric patients. AIMS: The present study aims to assess the prevalence of red cell antibodies in healthy blood donors at a tertiary care hospital-based blood bank in India...
January 2018: Asian Journal of Transfusion Science
Mei Liu, Qiang Guo, Chunmei Wu, Delphine Sterlin, Shyamal Goswami, Ying Zhang, Teng Li, Chunde Bao, Nan Shen, Qiong Fu, Xiaoming Zhang
A hallmark of systemic lupus erythematosus (SLE) is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies; however, the antibody-independent features of the B-cell compartment in SLE are less understood. In this study, we performed an extensive examination of B-cell subsets and their proinflammatory properties in a Chinese cohort of new-onset SLE patients. We observed that SLE patients exhibited an increased frequency of transitional B cells compared with healthy donors and rheumatoid arthritis patients...
March 21, 2018: Cellular & Molecular Immunology
Joan T Merrill, William R Shanahan, Morton Scheinberg, Kenneth C Kalunian, David Wofsy, Renee S Martin
BACKGROUND: Targeted inhibitors of B-cell activating factor (BAFF) have been evaluated in phase III trials in over 4000 patients with systemic lupus erythematosus (SLE). Post hoc analyses of these studies identify greater treatment effect in patients entering with higher disease activity, greater corticosteroid doses, anti double-stranded DNA (dsDNA) and low complement C3 or C4. OBJECTIVES: To evaluate the efficacy and safety of blisibimod, a BAFF inhibitor, in a population of patients with SLE enriched for high disease activity...
March 21, 2018: Annals of the Rheumatic Diseases
Ted R Mikuls, Clay Walker, Fang Qiu, Fang Yu, Geoffrey M Thiele, Barnett Alfant, Eric C Li, Lisa Y Zhao, Gary P Wang, Susmita Datta, Jeffrey B Payne
Objectives: To profile and compare the subgingival microbiome of RA patients with OA controls. Methods: RA (n = 260) and OA (n = 296) patients underwent full-mouth examination and subgingival samples were collected. Bacterial DNA was profiled using 16 S rRNA Illumina sequencing. Following data filtering and normalization, hierarchical clustering analysis was used to group samples. Multivariable regression was used to examine associations of patient factors with membership in the two largest clusters...
March 19, 2018: Rheumatology
Thanisorn Sukakul, Supenya Varothai
Pemphigus vegetans is a rare variant of deep acantholytic pemphigus which usually presents with vesiculobullous rash and vegetative plaques on the folds. We report a case of pemphigus vegetans patient who presented with rashes on tips of fingers and toes resembling paronychia and onychomadesis that misled the diagnosis for months. The final diagnosis of Hallopeau-type pemphigus vegetans was made based on histopathology and direct immunofluorescence studies. Interestingly, not only the clinical presentation was atypical, but blood tests for anti-desmoglein 1 and 3 antibodies by ELISA technique were also negative...
2018: Case Reports in Medicine
Ioanna Petta, Judith Fraussen, Veerle Somers, Markus Kleinewietfeld
B cells possess a predominant role in adaptive immune responses via antibody-dependent and -independent functions. The microbiome of the gastrointestinal tract is currently being intensively investigated due to its profound impact on various immune responses, including B cell maturation, activation, and IgA antibody responses. Recent findings have demonstrated the interplay between dietary components, gut microbiome, and autoantibody production. "Western" dietary patterns, such as high fat and high salt diets, can induce alterations in the gut microbiome that in turn affects IgA responses and the production of autoantibodies...
2018: Frontiers in Immunology
Cynthia Louis, Chris Burns, Ian Wicks
The pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is driven by genetic predisposition and environmental triggers that lead to dysregulated immune responses. These include the generation of pathogenic autoantibodies and aberrant production of inflammatory cytokines. Current therapies for RA and other autoimmune diseases reduce inflammation by targeting inflammatory mediators, most of which are innate response cytokines, resulting in generalized immunosuppression...
2018: Frontiers in Immunology
Laura M Jacobsen, Michael J Haller, Desmond A Schatz
While the incidence of type 1 diabetes continues to rise by 3% each year, the ability to prevent this disease remains elusive. Hybrid closed loop devices, artificial pancreas systems, and continuous glucose monitoring technology have helped to ease the daily burden for many people living with type 1 diabetes. However, the artificial pancreas is not a cure; more research is needed to achieve our ultimate goal of preventing type 1 diabetes. The preceding decades have generated a wealth of information regarding the natural history of pre-type 1 diabetes...
2018: Frontiers in Endocrinology
Petrus Linge, Paul R Fortin, Christian Lood, Anders A Bengtsson, Eric Boilard
Dysregulation of lymphocyte function, accumulation of autoantibodies and defective clearance of circulating immune complexes and apoptotic cells are hallmarks of systemic lupus erythematosus (SLE). Moreover, it is now evident that an intricate interplay between the adaptive and innate immune systems contributes to the pathogenesis of SLE, ultimately resulting in chronic inflammation and organ damage. Platelets circulate in the blood and are chiefly recognized for their role in the prevention of bleeding and promotion of haemostasis; however, accumulating evidence points to a role for platelets in both adaptive and innate immunity...
March 21, 2018: Nature Reviews. Rheumatology
Xinhua Yu, Reza Akbarzadeh, Mario Pieper, Thomas Scholzen, Stefanie Gehrig, Carsten Schultz, Detlef Zillikens, Peter König, Frank Petersen
Although uncontrolled proteolytic activity mediated by activated neutrophils is a major reason for tissue damage, therapeutic approaches using protease inhibitors are inefficient. Here, we investigated the role of the immune complex-induced neutrophil adhesion and protease release in tissue damage. We show both in vitro and in vivo that immune complex-mediated neutrophil adhesion to the target tissue depends on β2 integrins. Without affecting elastase or ROS release, blocking of adhesion drastically inhibited tissue damage in an experimental model of autoantibody-mediated skin blistering disease...
March 17, 2018: Journal of Investigative Dermatology
Magdalena Dryglewska, Bogdan Kolarz, Maria Majdan
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that results in uncontrolled immune system activation and overproduction of autoantibodies. The pathogenesis of the disease is complex and not fully understood, nevertheless, genetic and environmental factors play an important role. So far, about 30 genes have been identified to be involved in the SLE pathomechanism. However, not all genetically predisposed individuals develop the disease. This phenomenon can be associated with epigenetic changes that occur under the influence of environmental factors...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Yixuan Zhang, Muhammad Hussain, Xiuqin Yang, Peng Chen, Yaping Tian, Hongwu Du
BACKGROUND: Sjögren's syndrome (SS) is a systemic and chronic autoimmune disorder that affects the exocrine glands, with massive autoantibody production. Although the pathogenesis of the disorder is incompletely understood, some studies have reported that anti-moesin antibodies have been detected in autoimmune diseases with which SS is closely associated. Nevertheless, little is known about moesin's potential involvement in SS. OBJECTIVE: This study aims to verify whether moesin is a specific autoantigen involved in Chinese Hans SS patients...
March 19, 2018: Protein and Peptide Letters
Susan Malkiel, Ashley N Barlev, Yemil Atisha-Fregoso, Jolien Suurmond, Betty Diamond
Plasma cells (PCs) are responsible for the production of protective antibodies against infectious agents but they also produce pathogenic antibodies in autoimmune diseases, such as systemic lupus erythematosus (SLE). Traditionally, high affinity IgG autoantibodies are thought to arise through germinal center (GC) responses. However, class switching and somatic hypermutation can occur in extrafollicular (EF) locations, and this pathway has also been implicated in SLE. The pathway from which PCs originate may determine several characteristics, such as PC lifespan and sensitivity to therapeutics...
2018: Frontiers in Immunology
A C Jemilohun, O G Adewoye
Autoimmune hepatitis (AIH) is a rare cause of chronic liver disease (CLD). It presents with varied clinical features from acute hepatitis to CLDs like chronic viral hepatitis and alcoholic liver disease, making it difficult to diagnose in the absence of a high index of suspicion and adequate laboratory support. Autoantibody-mediated hepatocyte injury is the major feature of AIH. We present a 44 year old woman with recurrent jaundice, ascites, splenomegaly, coagulopathy, negative chronic viral hepatitis screening, elevated IgG and positive anti-smooth muscle antibody...
December 2017: Annals of Ibadan Postgraduate Medicine
Hanna D Bremer, Nils Landegren, Ronald Sjöberg, Åsa Hallgren, Stefanie Renneker, Erik Lattwein, Dag Leonard, Maija-Leena Eloranta, Lars Rönnblom, Gunnel Nordmark, Peter Nilsson, Göran Andersson, Inger Lilliehöök, Kerstin Lindblad-Toh, Olle Kämpe, Helene Hansson-Hamlin
Dogs can spontaneously develop complex systemic autoimmune disorders, with similarities to human autoimmune disease. Autoantibodies directed at self-antigens are a key feature of these autoimmune diseases. Here we report the identification of interleukin enhancer-binding factors 2 and 3 (ILF2 and ILF3) as autoantigens in canine immune-mediated rheumatic disease. The ILF2 autoantibodies were discovered in a small, selected canine cohort through the use of human protein arrays; a method not previously described in dogs...
March 19, 2018: Scientific Reports
Junli Liu, Xinfang Huang, Shumeng Hao, Yan Wang, Manman Liu, Jing Xu, Xingli Zhang, Tao Yu, Shucheng Gan, Dongfang Dai, Xuan Luo, Qingyan Lu, Chaoming Mao, Yanyun Zhang, Nan Shen, Bin Li, Mingzhu Huang, Xiaodong Zhu, Jin Jin, Xuhong Cheng, Shao-Cong Sun, Yichuan Xiao
Systemic lupus erythematosus (SLE) is characterized by uncontrolled secretion of autoantibodies by plasma cells. Although the functional importance of plasma cells and autoantibodies in SLE has been well established, the underlying molecular mechanisms of controlling autoantibody production remain poorly understood. Here we show that Peli1 has a B cell-intrinsic function to protect against lupus-like autoimmunity in mice. Peli1 deficiency in B cells induces autoantibody production via noncanonical NF-κB signaling...
March 19, 2018: Nature Communications
Larissa Seifert, Elion Hoxha, Anna M Eichhoff, Gunther Zahner, Silke Dehde, Linda Reinhard, Friedrich Koch-Nolte, Rolf A K Stahl, Nicola M Tomas
Background Thrombospondin type 1 domain-containing 7A (THSD7A) has been identified as a pathogenic autoantigen in membranous nephropathy (MN). However, the THSD7A epitopes targeted by patient autoantibodies are unknown. Methods We performed an in silico analysis of the THSD7A multidomain structure, expressed the folded domains in HEK293 cells, and tested for domain reactivity with 31 serum samples from patients with THSD7A-associated MN using Western and native blotting. Immunogenicity of the antigen domains was further investigated by cDNA immunization of rabbits and mice...
March 19, 2018: Journal of the American Society of Nephrology: JASN
Mark W Cunningham, Javier Castillo, Tarek Ibrahim, Denise C Cornelius, Nathan Campbell, Lorena Amaral, Venkata Ramana Vaka, Nathan Usry, Jan M Williams, Babbette LaMarca
Women with preeclampsia produce AT1-AA (agonistic autoantibodies to the angiotensin II type 1 receptor), which stimulate reactive oxygen species, inflammatory factors, and hypertensive mechanisms (ET [endothelin] and sFlt-1 [soluble fms-like tyrosine kinase-1]) in rodent models of preeclampsia. The placental ischemic reduced uterine perfusion pressure (RUPP) rat model of preeclampsia exhibits many of these features. In this study, we examined the maternal outcomes of AT1-AA inhibition ('n7AAc') in RUPP rats...
March 19, 2018: Hypertension
Henry H Nguyen, Abdel Aziz Shaheen, Natalia Baeza, Ellina Lytvyak, Stefan J Urbanski, Andrew L Mason, Gary L Norman, Marvin J Fritzler, Mark G Swain
BACKGROUND AND AIMS: Up to 20% of Primary Biliary Cholangitis (PBC) patients are estimated to have features that overlap with Autoimmune Hepatitis (AIH). Patients with PBC-AIH overlap syndrome (PBC-AIH OS) have been reported to exhibit suboptimal responses to ursodeoxycholic acid therapy, and are more likely to progress to cirrhosis. Anti-double stranded DNA (anti-dsDNA) and anti-p53 have been previously suggested to be potential autoantibodies for identifying patients with PBC-AIH OS...
2018: PloS One
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