A Comparison of Immunoglobulin Variable Region N-Linked Glycosylation in Healthy Donors, Autoimmune Disease and Lymphoma

N-linked glycans play an important role in immunity. Although the role of N-linked glycans in the Fragment crystallizable (Fc) region of immunoglobulins has been thoroughly described, the function of N-linked glycans present in Ig-variable domains is only just being appreciated. Most of the N-linked glycans harbored by immunoglobulin variable domain are of the complex biantennary type and are found as a result of the presence of N-linked glycosylation that most often have been introduced by somatic hypermutation. Furthermore, these glycans are ubiquitously present on autoantibodies observed in some autoimmune diseases as well as certain B-cell lymphomas. For example, variable domain glycans are abundantly found by anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) as well as by the B-cell receptors of follicular lymphoma (FL). In FL, variable domain glycans are postulated to convey a selective advantage through interaction with lectins and/or microbiota, whereas the contribution of variable domain glycans on autoantibodies is not known. To aid the understanding how these seemingly comparable phenomena contribute to a variety of deranged B-responses in such different diseases this study summarizes the characteristics of ACPA and other auto-antibodies with FL and healthy donor immunoglobulins, to identify the commonalities and differences between variable domain glycans in autoimmune and malignant settings. Our finding indicate intriguing differences in v...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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We report the case of a 65-year-old man with RA suffering from pain and swelling of left sternoclavicular (SC) joint, which was not relieved by adding low-dose glucocorticoid. Magnetic resonance imaging (MRI) showed a para-osseous soft tissue swelling around the SC joint and a fracture of proximal clavicle. Histology of the soft tissue demonstrated diffuse large B-cell lymphoma and the patient subsequently underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. He was successfully treated with six cycles of R-CHOP chemotherapy, with discontinuation of MTX, resulting in a com...
Source: Rheumatology International - Category: Rheumatology Source Type: research
CONCLUSIONS: Testing for autoantibodies against both Ro peptides may aim diagnosis, classify clinical manifestations in disease entities and define prognosis in certain autoimmune disorders. A distinct weight could be given to the isolated anti-Ro specificities in the SS classification criteria. PMID: 32083547 [PubMed - as supplied by publisher]
Source: Clinical and Experimental Rheumatology - Category: Rheumatology Tags: Clin Exp Rheumatol Source Type: research
Abstract Methotrexate (MTX)-associated classical Hodgkin lymphoma (CHL) is unlikely to regress following discontinuation of MTX, and its treatment usually requires chemotherapy. Standard chemotherapy for CHL is the ABVD regimen, which contains pneumotoxic bleomycin. This can be problematic in MTX-CHL patients suffering from an autoimmune disease (AID), such as rheumatoid arthritis (RA), as they frequently have pulmonary complications. However, brentuximab vedotin (BV)-containing chemotherapy without bleomycin (A + AVD regimen) was recently reported to show favorable efficacy for CHL, and could therefore ...
Source: International Journal of Hematology - Category: Hematology Authors: Tags: Int J Hematol Source Type: research
ConclusionsOur patient ’s case highlights the importance of assessing the clonal relationships of the lymphoid components of a composite lymphoma and Epstein-Barr virus screening in mucosa-associated lymphoid tissue lymphoma in patients with autoimmune disease.
Source: Journal of Medical Case Reports - Category: General Medicine Source Type: research
Publication date: Available online 7 January 2020Source: Autoimmunity ReviewsAuthor(s): Khalaf Kridin, A. Razzaque AhmedAbstractRituximab is a B cell depleting monoclonal antibody that targets the B cell-specific cell surface antigen CD20 and is currently used to treat several autoimmune diseases. The elimination of mature CD20-positive B lymphocytes committed to differentiate into autoantibody-producing plasma cells is considered to be the major effect of rituximab, that makes it a beneficial biological agent in treating autoimmune diseases. Hypogammaglobulinemia has been reported after rituximab therapy in patients with ...
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
Sjögren's syndrome: Old and new therapeutic targets. J Autoimmun. 2019 Dec 09;:102364 Authors: Mavragani CP, Moutsopoulos HM Abstract Sjögren's syndrome (SS) is a prototype autoimmune disease characterized by oral and ocular mucosal dryness following chronic inflammation of salivary and lachrymal glands, respectively. Profound B cell hyperactivity along with systemic manifestations including fatigue, musculoskeletal complaints, features related to hepatic, pulmonary, renal and nervous system involvement, as well as lymphoma development can be also present. Despite that activation of both inn...
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research
ObjectiveMucosa ‐associated lymphoid tissue lymphoma translocation protein 1 (MALT‐1) plays a crucial role in innate and adaptive immune signaling by modulating the threshold for activation of immune cells, including Treg cells. Therefore, MALT‐1 is regarded to be an interesting therapeutic target in several immune‐mediated diseases. The goal of this study was to examine the role of MALT‐1 in experimental animal models of rheumatoid arthritis (RA).MethodsMALT ‐1 activation was assessed by measuring cleavage of the deubiquitinase CYLD in lymphocytes from mice with collagen‐induced arthritis (CIA). Furthermore,...
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Original Article Source Type: research
Authors: Ciccacci C, Latini A, Perricone C, Conigliaro P, Colafrancesco S, Ceccarelli F, Priori R, Conti F, Perricone R, Novelli G, Borgiani P Abstract Autoimmune diseases (AIDs) are complex diseases characterized by persistent or recurrent inflammation, alteration of immune response, and production of specific autoantibodies. It is known that different AIDs share several susceptibility genetic loci. Tumor necrosis factor alpha inducible protein 3 (TNFAIP3) encodes the ubiquitin-modifying enzyme A20, which downregulates inflammation by restricting NF-κB, a transcription factor that regulates expression of var...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
Authors: Moll J, Isailovic N, De Santis M, Selmi C Abstract BACKGROUND: Serum rheumatoid factors are autoantibodies of different isotypes directed against the Fc fraction of immunoglobulin G (IgG) and represent paradigmatic autoantibodies that have been largely used in clinical practice for decades. Traditionally IgG has been associated with rheumatoid arthritis and more recently included also in the classification criteria for Sjӧgren's syndrome. Researchers have established that rheumatoid factors are positive in a variety of infectious, autoimmune, and neoplastic disorders, thus requiring a comprehensive evalua...
Source: The Israel Medical Association Journal - Category: General Medicine Tags: Isr Med Assoc J Source Type: research
ConclusionThis systematic review and conventional meta-analysis demonstrated the overall similarity of the long-term efficacy and safety of biosimilar rituximab to those of originator rituximab in RA and NHL patients by combining direct evidence from head-to-head trials.PROSPERO registration No. CRD42019125138.
Source: BioDrugs - Category: Drugs & Pharmacology Source Type: research
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