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Systemic Lupus Erythematosus
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Vaneet K. Sandhu, Neha V. Chiruvolu, Daniel J. Wallace
Some of the clinical manifestations commonly seen in SLE can be due to tissue damage from improper regulation or excessive production of IFN-1, with damage accumulating over time.34 The exact mechanism is unclear; however, several mechanisms have been proposed. IFN can promote activation of self-reactive T cells and induce BlyS, thus leading to B cell differentiation and immunoglobulin class switching. Skin biopsies from patients with SLE showed pDCs and MXI, rich in IFIG. There is substantial evidence of the association between IFN and renal and cardiovascular damage typically seen in SLE.34 In the early 2000s, presence of the IFN signature was correlated with increased disease activity (SLEDAI score), but the marker was too nonspecific to use in clinical studies.
Molecular Mechanisms Controlling Immunoglobulin E Responses
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Rachel L. Miller, Paul B. Rothman
The second type of signal responsible for Ig class switching involves cytokine-induced expression of particular germline CH transcripts via cytokine activation of the corresponding germline promoter. Immunoglobulin class switching has been shown to be preceded by the expression of germline transcripts in the area surrounding the switch region. Also, certain cytokines have been shown to regulate specific Ig class switching differentially through the induction of particular germline transcripts. For example, it has been demonstrated that the addition of IL-4 to lipopolysaccharide (LPS) cultures of B cells induces high levels of germline ∈ and γI transcripts that correlate with the amount of IgE and IgG1 induction, respectively [76,78]. More recently, IL-13 has been shown to induce germline IgE heavy-chain gene transcription in purified B cells, even in the presence of neutralizing anti-IL-4 antibody, confirming its independent role in IgE production [25]. In contrast, IFN-γ has been shown to suppress the IL-4-induced germline e transcription. Furthermore, regulation of IgE switching seems to occur through these cytokines’ antagonistic effects on the germline ∈ promoter [79]. These observations seem to support a model in which specific heavy-chain germline transcription always precedes switch recombination and in which type 1 versus type 2 cytokines differentially regulate the switching process to C∈.
Effects of Retinoids at the Systemic Level
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
Sandra Maria Barbalho, Letícia Maria Pescinini-Salzedas
In B cells, the central immune regulatory role of RA is related to immunoglobulin class switching. The RA produced in DC in enterocytes induces the generation of IgA+ producing B cell and redoubles memory B-cell differentiation. These actions result in a severe increase both in the intestinal and serum IgA levels. RA also downregulates TH2 and IgE immune responses (9).
Prevalence of healthcare workers fully vaccinated against hepatitis B without circulating antibodies in Italy and role of age at baseline cycle vaccination: a systematic review and meta-analysis
Published in Expert Review of Vaccines, 2023
Francesco Paolo Bianchi, Pasquale Stefanizzi, Giovanni Migliore, Andrea Martinelli, Luigi Vimercati, Cinzia Annatea Germinario, Silvio Tafuri
Considering the age of vaccination, our systematic review showed that subjects vaccinated during adolescence and adulthood reported a higher prevalence of circulating antibodies than those vaccinated in infancy (regardless of the time elapsed from the last vaccine dose to antibody evaluation); this evidence has been confirmed by our meta-analysis, which estimated a RR of 0.30 (95%CI = 0.25–0.37). In fact, the infant immune system is considered immature, with a restricted immunoglobulin repertoire that exhibits low-affinity antibody responses and impaired T-cell function with poor B-cell and T-cell interaction. The Th2/regulatory T cell-type response and reduced somatic hypermutation of B cells, which predominate in early infancy, result in reduced immune tolerance and humoral response, which transitions to a Th1-type response and progressive maturation of immunoglobulin class switching and related responses during the first year of life [16]. In addition, the administration of more immunogenic vaccines in adolescence/adulthood than in childhood may be another explanation [17]. Moreover, our sub-group analysis per professional category revealed more than twice the prevalence of subjects without circulating antibodies among students/residents compared with HCWs; actually, professional category is a proxy for the real risk factor, that is, the age of vaccination. Indeed, most HCWs have been vaccinated during adolescence/adulthood, while most students/residents during infancy.
Anti-interferon-gamma autoantibody related disseminated nontuberculous mycobacteriosis with pathological features of immunoglobulin G4-related disease
Published in Immunological Medicine, 2022
Norihiro Nagamura, Toshihiro Imada
IgG4-RD is an immune-mediated fibro-inflammatory disorder of organ enlargement with high serum IgG4 concentration and IgG4-positive plasma cell infiltration in the involved organs [1]. Immunoglobulin class switching depending on IL-4, 10, 13 and transforming growth factor-β (TGF-β), which act as Th2 and Treg response is considered the basic immunological reaction of this disorder [3,19]. Most of the histopathological features of IgG4-RD are associated with Th2-dominant and upregulated Treg cells [20]. Increased these associated cytokine expression was proven in several involved organs of IgG4-RD [2,3,21]. Concerning the patient’s renal pathology, it showed increased IgG4/IgG ratio and IgG4 positive plasma cell count enough to meet the comprehensive diagnostic criteria for IgG4-RD. However, characteristic storiform fibrosis, so called Bird’s eye pattern could not be detected and diagnostic criteria for IgG4 related kidney disease was not fulfilled definitely.
Primary cutaneous indolent B-cell lymphomas – a retrospective multicenter analysis and a review of literature
Published in Acta Oncologica, 2021
Magdalena Olszewska-Szopa, Marta Sobas, Kamel Laribi, Laura Bao Perez, Joanna Drozd-Sokołowska, Edyta Subocz, Monika Joks, Krzysztof Zduniak, Małgorzata Gajewska, Anna Kulikowska de Nalecz, Joanna Romejko-Jarosińska, Beata Kumiega, Anna Waszczuk-Gajda, Tomasz Wróbel, Anna Czyz
Indolent PCBCLs affect primarily adults at the age of 40–60 years. The pathogenesis of these lymphomas remains unclear. The potential role of infections in PCMZL etiopathology was suggested by some authors but has not been clearly confirmed yet [3]. The disease localizes preferably within the trunk, head and arms, with lesions that are heterogeneous in their appearance. Large wedge-shaped biopsy and excision biopsy, which enable histological analysis are the golden standard in the diagnostic process. CT scans are the recommended imaging studies although they are not reliable in cutaneous lesions assessment [4]. Bone marrow examination is not a part of the routine diagnostic workup in indolent PCBCLs. Histologically indolent PCBCLs usually differ from their systemic equivalents [2,5]. Only a small subset of PCMZLs shows diffuse proliferation of B cells while a vast majority of cases show evidence of immunoglobulin class switching. There is some evidence that t(14;18) and Bcl-2 expression may be useful for differentiation between PCFCL and systemic FL [6]. Both TNM and Ann Arbor classification does not appear as useful and reliable in the PCBCLs staging process, as in systemic lymphomas. In 2011 International Extranodal Lymphoma Study Group proposed a new tool for risk stratification, the Cutaneous Lymphoma International Prognostic Index – CLIPI (Supplementary file). However generally, indolent PCBCLs are characterized by a very good prognosis, since 5-year disease-specific survival is as high as 99% for PCMZL and 95% for PCFCL [1].