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Wei Huang, Jiyuan Wu, Huiqin Yang, Yin Xiong, Rui Jiang, Tianpen Cui, Duyun Ye
Abnormal features of the systemic lupus erythematosus (SLE)-derived neutrophils, promoted aberrant immune response, have inspired new studies of the induction of autoimmunity and the development of organ damage in SLE. In this study, we explore the effect of milk fat globule-EGF factor 8 (MFG-E8) on the aberrant nitrification features in pristane-induced lupus. SLE patients and mice with pristane-induced lupus develop autoantibodies associated with MFG-E8 overproduction. However, the deletion of MFG-E8 leads to uncontrolled early pulmonary and peritoneal inflammation and tissue damage in mice with pristane-induced lupus...
October 21, 2016: Cell Death and Differentiation
Ewa Papuć, Konrad Rejdak
There is emerging evidence that glial cells are involved in the neuropathological process in Parkinson's disease (PD) in addition to degeneration of neuronal structures. Recently, we confirmed the presence of an adaptive immune response against different glial-derived antigens in PD, with a possible role of anti-MAG, anti-MBP and anti-PLP antibodies in the disease progression. The aim of the present study was to assess humoral response against myelin-associated glycoprotein (MAG) in patients with parkinsonism (both idiopathic and atypical) to check whether these antibodies could serve as biomarkers of PD, its severity and progression...
October 20, 2016: Journal of Neural Transmission
Fatima El-Assaad, Steven A Krilis, Bill Giannakopoulos
The antiphospholipid syndrome (APS) is an autoimmune disease characterised by a procoagulant state that predisposes to recurrent thrombosis and miscarriages. Two major discoveries have advanced our understanding of the underlying complex pathogenesis of the APS. The first was the discovery that beta-2 glycoprotein-1 (β2GPI) is the major auto antigen in APS. The second was the discovery in more recent years that β2GPI contains allosteric disulphide bonds susceptible to posttranslational modification that may be involved in the development of autoantibodies in APS...
2016: Thrombosis Journal
Sanna Turunen, Johanna Huhtakangas, Tomi Nousiainen, Maarit Valkealahti, Jukka Melkko, Juha Risteli, Petri Lehenkari
BACKGROUND: Seropositive rheumatoid arthritis (RA) is characterized by autoantibodies binding to citrullinated and homocitrullinated proteins. We wanted to study the expression patterns of these disease-associated protein forms and if the rheumatoid nodule and synovial tissue itself contain biologically active levels of citrullinating peptidyl arginine deiminases 2, 3 and 4 and homocitrullination-facilitating neutrophil enzyme myeloperoxidase. METHOD: Total of 195 synovial samples from metatarsal joints from five ACPA/RF-positive RA patients (n = 77), synovial samples from knees of eight seropositive RA (n = 60), seven seronegative RA (n = 33) and five osteoarthritis (n = 25) patients were analyzed for citrulline and homocitrulline contents using HPLC...
October 20, 2016: Arthritis Research & Therapy
Christian M Felix, Marc H Levin, Alan S Verkman
BACKGROUND: Neuromyelitis optica (NMO), an autoimmune inflammatory disease of the central nervous system, is often associated with retinal abnormalities including thinning of the retinal nerve fiber layer and microcystic changes. Here, we demonstrate that passive transfer of an anti-aquaporin-4 autoantibody (AQP4-IgG) produces primary retinal pathology. METHODS: AQP4-IgG was delivered to adult rat retinas by intravitreal injection. Rat retinas and retinal explant cultures were assessed by immunofluorescence...
October 20, 2016: Journal of Neuroinflammation
M Cugno, A Tedeschi, B Frossi, F Bossi, A V Marzano, R Asero
: Background y Objective: Functionally active autoantibodies to IgE and to the high-affinity IgE receptor (FcεRI) can be detected in serum in about 40% of patients with chronic spontaneous urticaria (CSU). Recent studies showed that serum from patients with CSU can induce activation of mast cells, irrespective of whether they carry high-affinity IgE receptors. To evaluate mast cell activation induced by factors in the serum of CSU patients with a molecular weight lower than that of autoantibodies...
October 2016: Journal of Investigational Allergology & Clinical Immunology
I Mancini, I Ricaño-Ponce, E Pappalardo, A Cairo, M M Gorski, G Casoli, B Ferrari, M Alberti, D Mikovic, M Noris, C Wijmenga, F Peyvandi
BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor cleaving protease, ADAMTS13. Similarly to other autoimmune disorders, evidences of a genetic contribution have been reported, including the association of the human leukocyte antigen (HLA) class II complex with disease risk OBJECTIVE: To identify novel genetic risk factors in acquired TTP...
October 20, 2016: Journal of Thrombosis and Haemostasis: JTH
Angela Ceribelli, Natasa Isailovic, Maria De Santis, Elena Generali, Micaela Fredi, Ilaria Cavazzana, Franco Franceschini, Luca Cantarini, Minoru Satoh, Carlo Selmi
This study aims to characterize myositis-specific antibodies in a well-defined cohort of patients with idiopathic inflammatory myopathy and to determine their association with cancer. Sera from 40 patients with polymyositis, dermatomyositis, and controls were tested by protein and RNA immunoprecipitation to detect autoantibodies, and immunoprecipitation-Western blot was used for anti-MJ/NXP-2, anti-MDA5, and anti-TIF1γ/α identification. Medical records were re-evaluated with specific focus on cancer. Anti-MJ/NXP-2 and anti-TIF1γ/α were the most common antibodies in dermatomyositis...
October 20, 2016: Clinical Rheumatology
Masato Kadoya, Ayumi Hida, Meiko Hashimoto Maeda, Kenichiro Taira, Chiseko Ikenaga, Naohiro Uchio, Akatsuki Kubota, Kenichi Kaida, Yusuke Miwa, Kazuhiro Kurasawa, Hiroyuki Shimada, Masahiro Sonoo, Atsuro Chiba, Yasushi Shiio, Yoshikazu Uesaka, Yasuhisa Sakurai, Toru Izumi, Manami Inoue, Shin Kwak, Shoji Tsuji, Jun Shimizu
OBJECTIVE: To show cancer association is a risk factor other than statin exposure for anti-3-hydroxy-3-methylglutaryl coenzyme A reductase autoantibody-positive (anti-HMGCR Ab+) myopathy. METHODS: We analyzed the clinical features and courses of 33 patients (23 female and 10 male) with anti-HMGCR Ab+ myopathy among 621 consecutive patients with idiopathic inflammatory myopathies. RESULTS: Among the 33 patients, 7 (21%) were statin-exposed and 26 were statin-naive...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
Vahid Davoudi, Kiandokht Keyhanian, Riley M Bove, Tanuja Chitnis
Anti-aquaporin-4 (AQP4) autoantibody plays a key role in the pathogenesis of neuromyelitis optica (NMO). Studies have shown increased relapse rates in patients with NMO during pregnancy and postpartum. High estrogen levels during pregnancy can increase activation-induced cytidine deaminase expression, which is responsible for immunoglobulin production. Additionally, sex hormones may influence antibody glycosylation, with effects on antibody function. Estrogen decreases apoptosis of self-reactive B cells, through upregulation of antiapoptotic molecules...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
Stefan Tukaj, Anna Görög, Konrad Kleszczyński, Detlef Zillikens, Sarolta Kárpáti, Michael Kasperkiewicz
Inflammation-induced heat shock proteins (HSPs) and hypovitaminosis D have been reported to impact immune responses and to be associated with autoimmune diseases including celiac disease (CD), a gluten-sensitive enteropathy mediated by autoantibodies against tissue transglutaminase (TG2). Recently, we provided evidence for a role of autoantibodies to HSPs in patients with dermatitis herpetiformis (DH), an inflammatory skin disease induced by underlying latent CD. In this study, we aimed at investigating the humoral autoimmune response to HSPs and vitamin D status in CD patients (n=15) presenting without the cutaneous disease manifestation...
October 16, 2016: Journal of Steroid Biochemistry and Molecular Biology
Agnes Gardet, Wei C Chou, Taylor L Reynolds, Diana B Velez, Kai Fu, Julia M Czerkowicz, Jeffrey Bajko, Ann M Ranger, Normand Allaire, Hannah M Kerns, Sarah Ryan, Holly M Legault, Robert W Dunstan, Robert Lafyatis, Matvey Lukashev, Joanne L Viney, Jeffrey L Browning, Dania Rabah
Mouse models lupus nephritis (LN) have provided important insights into disease pathogenesis, although none have been able to recapitulate all features of the human disease. Using comprehensive longitudinal analyses, we characterized a novel accelerated mouse model of lupus using pristane treatment in SNF1 (SWR X NZB F1) lupus prone mice (pristane-SNF1 mice). Pristane treatment in SNF1 mice accelerated the onset and progression of proteinuria, autoantibody production, immune complex deposition and development of renal lesions...
2016: PloS One
Stuart G Tangye
Some autoimmune disorders are monogenetic diseases; however, clinical manifestations among individuals vary, despite the presence of identical mutations in the disease-causing gene. In this issue of the JCI, Massaad and colleagues characterized a seemingly monogenic autoimmune disorder in a family that was linked to homozygous loss-of-function mutations in the gene encoding the endonuclease Nei endonuclease VIII-like 3 (NEIL3), which has not been previously associated with autoimmunity. The identification of an unrelated healthy individual with the same homozygous mutation spurred more in-depth analysis of the data and revealed the presence of a second mutation in a known autoimmune-associated gene...
October 17, 2016: Journal of Clinical Investigation
Michel J Massaad, Jia Zhou, Daisuke Tsuchimoto, Janet Chou, Haifa Jabara, Erin Janssen, Salomé Glauzy, Brennan G Olson, Henner Morbach, Toshiro K Ohsumi, Klaus Schmitz, Markianos Kyriacos, Jennifer Kane, Kumiko Torisu, Yusaku Nakabeppu, Luigi D Notarangelo, Eliane Chouery, Andre Megarbane, Peter B Kang, Eman Al-Idrissi, Hasan Aldhekri, Eric Meffre, Masayuki Mizui, George C Tsokos, John P Manis, Waleed Al-Herz, Susan S Wallace, Raif S Geha
Alterations in the apoptosis of immune cells have been associated with autoimmunity. Here, we have identified a homozygous missense mutation in the gene encoding the base excision repair enzyme Nei endonuclease VIII-like 3 (NEIL3) that abolished enzymatic activity in 3 siblings from a consanguineous family. The NEIL3 mutation was associated with fatal recurrent infections, severe autoimmunity, hypogammaglobulinemia, and impaired B cell function in these individuals. The same homozygous NEIL3 mutation was also identified in an asymptomatic individual who exhibited elevated levels of serum autoantibodies and defective peripheral B cell tolerance, but normal B cell function...
October 17, 2016: Journal of Clinical Investigation
Katrin Lorenz, Sabine Beck, Munir M Keilani, Joanna Wasielica-Poslednik, Norbert Pfeiffer, Franz H Grus
BACKGROUND: The aim of our current investigation was to analyze the autoantibody -reactivities of patients after acute angle closure glaucoma (AACG) by means of a protein microarray approach to identify intraocular pressure (IOP)-dependent antibodies. METHODS: Collected sera from different study time points (AACG n = 6, 0, 2, 4 and 12 weeks) and control group (CTRL n = 11, 0 and 12 weeks) were analyzed. Protein-microarrays were incubated with sera and occurring immunoreactivities were visualized with fluorescence labeled anti-human-IgG antibodies...
October 18, 2016: Clinical & Experimental Ophthalmology
Surjit Singh, Pramod Kumar Sharma
Here, we present a case of chronic myeloid leukemia for which imatinib therapy was initated. Triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone was normal, and thyroid microsomal autoantibodies (TMA) were positive and patient was diagnosed as thyroiditis treated with corticosteroids for 1½ months which lead to resolution.
July 2016: Indian Journal of Pharmacology
Sohei Kobayashi, Tyuji Hoshino, Takaki Hiwasa, Mamoru Satoh, Bahityar Rahmutulla, Sachio Tsuchida, Yuji Komukai, Tomoaki Tanaka, Hisahiro Matsubara, Hideaki Shimada, Fumio Nomura, Kazuyuki Matsushita
Anti-PUF60, poly(U)-binding-splicing factor, autoantibodies are reported to be detected in the sera of dermatomyositis and Sjogren's syndrome that occasionally associated with malignancies. PUF60 is identical with far-upstream element-binding protein-interacting repressor (FIR) that is a transcriptional repressor of c-myc gene. In colorectal cancers, a splicing variant of FIR that lacks exon2 (FIRΔexon2) is overexpressed as a dominant negative form of FIR. In this study, to reveal the presence and the significance of anti-FIRs (FIR/FIRΔexon2) antibodies in cancers were explored in the sera of colorectal and other cancer patients...
October 15, 2016: Oncotarget
Pedro Pallangyo, Isaac Mawenya, Paulina Nicholaus, Henry Mayala, Amida Kalombola, Godwin Sharau, Naiz Majani, Mohamed Janabi
BACKGROUND: Congenital complete heart block is a life-threatening condition which is highly associated with autoimmune and connective tissue disorders. Presence of maternal autoantibodies for associated conditions increases the risk of delivering a child with congenital complete heart block, however, less than a half of all women with such antibodies are symptomatic even after delivery. Mortality rate is highest during the neonatal period (45 %) and about two-thirds of all cases will require permanent pacing at some point in their lives...
October 19, 2016: Journal of Medical Case Reports
Arsenio Spinillo, Fausta Beneventi, Elena Locatelli, Vèronique Ramoni, Roberto Caporali, Claudia Alpini, Giulia Albonico, Chiara Cavagnoli, Carlomaurizio Montecucco
BACKGROUND: The burden of pregnancy complications associated with well defined, already established systemic rheumatic diseases preexisting pregnancy such as rheumatoid arthritis, systemic lupus erythematosus or scleroderma is well known. Systemic rheumatic diseases are characterized by a long natural history with few symptoms, an undifferentiated picture or a remitting course making difficult a timely diagnosis. It has been suggested that screening measures for these diseases could be useful but the impact of unrecognized systemic rheumatic disorders on pregnancy outcome is unknown...
October 18, 2016: BMC Pregnancy and Childbirth
Izabella Surowiec, Lisbeth Ärlestig, Solbritt Rantapää-Dahlqvist, Johan Trygg
OBJECTIVE: The early diagnosis of rheumatoid arthritis (RA) is desirable to install treatment to prevent disease progression and joint destruction. Autoantibodies and immunological markers pre-date the onset of symptoms by years albeit not all patients will present these factors, even at disease onset. Additional biomarkers would be of high value to improve early diagnosis and understanding of the process, leading to disease development. METHODS: Plasma samples donated before the onset of RA were identified in the Biobank of Northern Sweden, a collection within national health survey programs...
2016: PloS One
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