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Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by T cells imbalance. Indeed, a correlation between levels of Th17 cells and disease activity has been reported. Our work aimed to study the functional association of subpopulations of Th cells and SLE with (lupus nephritis, LN) or without (lupus erythematosus, LE) renal involvement in Tunisian patients through the detection of intracellular cytokines and surface marker expression. The IL23R and RORC mRNA expression levels were evaluated. The level of Th17 and Th1 cells was higher in LE and LN patients compared to healthy controls (HC) (p = 0.007 and p = 0.018, respectively), while Th1/17 cells were increased only in LN patients compared to HC (p = 0.011). However, no significant difference was described in the mRNA expression levels of RORC and IL-23R between SLE and HC. Our findings suggest that the Th1/Th17 differentiation mechanisms are altered in SLE and that this imbalance should have an important influence on the development and severity of the disease.

Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine involved in host defense against infections and regulates the innate and acquired immune response. IL-18 is produced by both hematopoietic and non-hematopoietic cells, including monocytes, macrophages, keratinocytes and mesenchymal cell. IL-18 could potentially induce inflammatory and cytotoxic immune cell activities leading to autoimmunity. Its elevated levels have been reported in the blood of patients with some immune-related diseases, including rheumatoid arthritis, systemic lupus erythematosus, type I diabetes mellitus, atopic dermatitis, psoriasis, and inflammatory bowel disease. In the present review, we aimed to summarize the biological properties of IL-18 and its pathological role in different autoimmune diseases. We also reported some monoclonal antibodies and drugs targeting IL-18. Most of these monoclonal antibodies and drugs have only produced partial effectiveness or complete ineffectivenessin vitro,in vivoand human studies. The ineffectiveness of these drugs targeting IL-18 may be largely due to the loophole caused by the involvement of other cytokines and proteins in the signaling pathway of many inflammatory diseases besides the involvement of IL-18. Combination drug therapies, that focus on IL-18 inhibition, in addition to other cytokines, are highly recommended to be considered as an important area of research that needs to be explored.

Interleukin-17 (IL-17) is a proinflammatory cytokine involved in chronic inflammation occurring during the pathogenesis of allergy, malignancy, and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis. IL-17 is produced by multiple cell types of adaptive and innate immunity, including T helper 17 cells, CD8 + T cells, γδ T cells, natural killer T cells, and innate lymphoid cells. Monoclonal antibodies (mAbs) targeting IL-17 and/or IL-17R would be a potential approach to study this therapeutic tool for these diseases. In the current review, we aimed to highlight the characteristics of IL-17 and its important role in the pathogenesis of related diseases. Critical evaluation of the mAbs targeting IL-17A and IL-17 receptors (e.g., Ixekizumab, Secukinumab, and Brodalumab) in various immune-mediated diseases will be provided, and finally, their clinical efficacy and safety will be reported.

T helper 22 (Th22) cell populations are a newly identified subset of CD4+ T cells that primarily mediate biological effects on the epithelial barrier through interleukin (IL)-22. Although, new studies showed that both Th22 and IL-22 are closely associated with the pathogenesis of inflammatory, autoimmune and allergic disease as well as malignancies. In this review, we aim to describe the development and characteristics of Th22 cells as well as their roles in the immunopathogenesis of immune-related disorders and cancer. © 2021 The Scandinavian Foundation for Immunology

SARS‐CoV‐2 is a novel human coronavirus responsible for the Coronavirus disease 2019 (COVID‐19) pandemic. Pneumonia and acute respiratory distress syndrome are the major complications of COVID‐19. SARS‐CoV‐2 infection can activate innate and adaptive immune responses and result in massive inflammatory responses later in the disease. These uncontrolled inflammatory responses may lead to local and systemic tissue damage. In patients with severe COVID‐19, eosinopenia and lymphopenia with a severe reduction in the frequency of CD4+ and CD8+ T cells, B cells and natural killer (NK) cells are a common feature. COVID‐19 severity hinges on the development of cytokine storm characterized by elevated serum levels of pro‐inflammatory cytokines. Moreover, IgG‐, IgM‐ and IgA‐specific antibodies against SARS‐CoV‐2 can be detected in most patients, along with the viral RNA, forming the basis for assays that aid in patient diagnosis. Elucidating the immunopathological outcomes due to COVID‐19 could provide potential targets for immunotherapy and are important for choosing the best clinical management by consultants. Currently, along with standard supportive care, therapeutic approaches to COVID‐19 treatment involve the use of antiviral agents that interfere with the SARS‐CoV‐2 lifecycle to prevent further viral replication and utilizing immunomodulators to dampen the immune system in order to prevent cytokine storm and tissue damage. While current therapeutic options vary in efficacy, there are several molecules that were either shown to be effective against other viruses such as HIV or show promise in vitro that could be added to the growing arsenal of agents used to control COVID‐19 severity and spread.

Systemic lupus erythematosus (SLE) is a complex autoimmune inflammatory disease characterized by an unknown etiology and a highly variable clinical presentation. This clinical heterogeneity might be explained by dysregulation of tolerance to self and apoptotic mechanisms, overproduction of autoantibodies, and abnormal cytokine levels. Cytokine imbalance levels have been associated with disease activity and severity in SLE patients. In the last years, salivary cytokines related to SLE have gained significant attention and researchers have begun to focus on the identification of cytokines in the saliva of SLE patients using it as a diagnostic fluid for the inflammatory process underlying SLE. This review highlights and summarizes recent studies revealing the cytokines that have been identified in the saliva of individuals with SLE. Data reported and discussed in this report may provide useful additional information to better understand the mechanisms associated with the disease.

Within the pathophysiology of epilepsy, as a chronic brain disorder, the involvement of neuroinflammation has been extensively implied. Recurrent seizures of epilepsy have been associated with elevated levels of immune mediators that seem to play a pivotal role in triggering them. Neurons, glia, and endothelial cells of the blood-brain barrier (BBB) take part in such inflammatory processes by expressing receptors of associated mediators through autocrine and paracrine stimulation of intracellular signaling pathways. In this milieu, elevated cytokine levels in serum and brain tissue have been reported in patients with an epileptic profile. Noteworthy, interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) are the proinflammatory cytokines mostly associated, in literature, with the pathogenesis of epilepsies. In this review, we examine the function of these cytokines in connection with transforming growth factor-beta (TGF-β), IL-8, IL-12, IL-18, and macrophage inflammatory protein (MIP) as potential proinflammatory mediators in the neuropathology of epilepsy.

Background Anti-centromere auto-antibodies (ACA) have been described as a marker in Systemic sclerosis (SSc) disease. CENP-B is the major centromere auto-antigen recognized by SSc patients with positive ACA. Our aim was to characterize the major epitope involved in the anti-CENP-B immune response of Moroccan SSc patients. Patients and method For identification of SSc biomarkers, 80 sera from patients with SSc and systemic lupus erythematosus (SLE) were screened by indirect immunofluorescence test (IIF) to assess the presence of ANA reactivity. Immunoblotting analysis was performed for 11 sera with positive ACA using the N-terminal and C-terminal region of CENP-B protein as antigens. Results 29 out of 30 (96, 66 %) patients with SSc had positive ANA. 11 out of 30 (36, 67 %) patients were ACA positive and 6 of them produced auto-antibodies against Nt-CENPB antigen. Two of these 6 Nt-CENPB positive sera produced also other auto-antibodies associated to primary biliary cirrhosis. None of all sera tested showed reactivity against Ct-CENPB. Conclusion Our data showed, for the first time in Morocco, that the Nt-CENPB contains a major epitope for Moroccan SSc patients. These findings could provide additional information that would contribute to improving the diagnosis and management of these patients.

Rituximab (RTX), as a monoclonal antibody-based immunotherapeutic intervention targeting CD20 on B cells, has proven efficacy in the treatment of patients with some immune-mediated diseases. In the present review, we provided information on the immunobiological mechanisms of signaling for RTX and its clinical applications, according to the immune-pathophysiology involved in the microenvironment of multiple diseases. We highlighted combination therapy, dose schedules, and laboratory monitoring, as well as the associated common and rare side effects to avoid. We also discussed the efficacy and safety of RTX-based therapeutic strategies and whether RTX therapy can be used as a promising treatment regimen for autoimmune diseases, primary immunodeficiency diseases, and malignancies. Our review highlights and supports the importance of collaboration between basic medical researchers and clinical specialists when considering the use of RTX in the treatment of various immune-mediated disorders.