Advancing research on regulatory autoantibodies targeting GPCRs: Insights from the 5th international symposium.

The 5th International Symposium on Regulatory Autoantibodies Targeting GPCR (RAB-GPCRs) advanced the understanding of the significant role played by autoantibodies targeting G-protein-coupled receptors (GPCRs) in various human diseases. Once considered passive markers, RAB-GPCRs are now recognized as active modulators of cellular signaling, immune regulation, and inflammation. The symposium highlighted their involvement in multiple prominent pathologies, including autoimmune diseases, cardio- and cerebrovascular diseases, and neuroimmunologic disorders such as myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 syndrome (ME/CFS/PCS), as well as solid organ and hematopoietic stem cell transplantation (SOT/HSCT).

Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms.

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms.

Regulatory T cells inhibit autoantigen-specific CD4 T cell responses in lupus-prone NZB/W F1 mice.

Introduction: Progressive loss of regulatory T cell (Treg)-mediated control over autoreactive effector T cells contributes to the development of systemic lupus erythematosus (SLE). Accordingly, we hypothesized that Treg may also have the capacity to suppress the activation of autoreactive CD4 T cells that are considered to drive autoimmunity.

Methods: To investigate whether Treg are involved in the control of autoreactive CD4 T cells, we depleted CD25 Treg cells either or , or combined both approaches before antigen-specific stimulation with the SLE-associated autoantigen SmD1(83-119) in the NZB/W F1 mouse model either after immunization against SmD1(83-119) or during spontaneous disease development.

When natural antibodies become pathogenic: autoantibodies targeted against G protein-coupled receptors in the pathogenesis of systemic sclerosis.

Systemic sclerosis (SSc) is a chronic, multisystem connective tissue, and autoimmune disease with the highest case-specific mortality and complications among rheumatic diseases. It is characterized by complex and variable features such as autoimmunity and inflammation, vasculopathy, and fibrosis, which pose challenges in understanding the pathogenesis of the disease. Among the large variety of autoantibodies (Abs) present in the sera of patients suffering from SSc, functionally active Abs against G protein-coupled receptors (GPCRs), the most abundant integral membrane proteins, have drawn much attention over the last decades.

Autoantibodies targeting G protein-coupled receptors: An evolving history in autoimmunity. Report of the 4th international symposium.

G protein-coupled receptors (GPCR) are involved in various physiological and pathophysiological processes. Functional autoantibodies targeting GPCRs have been associated with multiple disease manifestations in this context. Here we summarize and discuss the relevant findings and concepts presented in the biennial International Meeting on autoantibodies targeting GPCRs (the 4th Symposium), held in Lübeck, Germany, 15-16 September 2022.

Low-dose interleukin-2 therapy: a promising targeted therapeutic approach for systemic lupus erythematosus.

Purpose Of Review: Low-dose interleukin-2 (IL-2) therapy is increasingly recognized as a promising novel therapeutic concept in inflammatory and autoimmune diseases, in particular in systemic lupus erythematosus (SLE). As IL-2 is indispensable for the growth and survival of regulatory T cells (Treg), deficiency of this regulatory cytokine plays a significant role in immune dysregulation and breach of tolerance in SLE. Recovery of Treg activity by low-dose IL-2 therapy directly interferes with the immune pathology in SLE and thus can be considered a targeted treatment approach with a unique and physiological mode of action.

Autoimmune pre-disease.

Approximately 5% of the world-wide population is affected by autoimmune diseases. Overall, autoimmune diseases are still difficult to treat, impose a high burden on patients, and have a significant economic impact. Like other complex diseases, e.

Dysregulation and chronicity of pathogenic T cell responses in the pre-diseased stage of lupus.

In the normal immune system, T cell activation is tightly regulated and controlled at several levels to ensure that activation occurs in the right context to prevent the development of pathologic conditions such as autoimmunity or other harmful immune responses. CD4FoxP3 regulatory T cells (Treg) are crucial for the regulation of T cell responses in the peripheral lymphatic organs and thus for the prevention and control of autoimmunity. In systemic lupus erythematosus (SLE), a prototypic systemic autoimmune disease with complex etiology, a disbalance between Treg and pathogenic effector/memory CD4 T cells develops during disease progression indicating that gradual loss of control over T cell activation is an important event in the immune pathogenesis.

Differential gene expression of BCL-2, ZEB2-AS1 and BALR-2 in prostate cancer and benign prostatic hyperplasia.

Prostate cancer (PCa) and benign prostate hyperplasia (BPH) are highly prevalent heterogeneous disorders among men. Whereas PCa and BPH underline common pathological features, apoptotic-related genes might be differentially expressed in these diseases. This study was aimed at testing BCL-2 as well as BALR-2 and ZEB2-AS1 apoptosis-related long non-coding RNA (lncRNA) in patients with PCa and BPH.

The MCP-1 rs1024611 and MTHFR rs1801133 gene variations and expressions in alopecia areata: A pilot study.

Background: Monocyte chemoattractant protein-1 (MCP-1) is highly expressed by lymphocytes at skin sites affected by alopecia areata (AA). Variations in MCP-1 as well as in methylene-tetrahydrofolate reductase (MTHFR), a key enzyme related to many inflammatory pathologies, have been associated with several autoimmune disorders. This study was designed to test a possible association between MCP-1 and MTHFR variations and altered expression of their genes and the risk of AA.

Involvement of single nucleotide polymorphisms in ovarian poor response.

Purpose: Unpredictability in acquiring an adequate number of high-quality oocytes following ovarian stimulation is one of the major complications in controlled ovarian hyperstimulation (COH). Genetic predispositions of variations could alter the immunological profiles and consequently be implicated in the variability of ovarian response to the stimulation.

Design: Uncovering the influence of variations in AMHR2, LHCGR, MTHFR, PGR, and SERPINE1 genes with ovarian response to gonadotrophin stimulation in COH of infertile women.

Aberrant expression of BAX, MEG3, and miR-214-3P genes in recurrent pregnancy loss.

Aims: Recurrent pregnancy loss (RPL), with unknown causes, is one of the most common challenges facing pregnancy. Apoptotic signaling pathways are involved in the normal and abnormal pregnancy process. Despite the evidence pointing toward the aberrant expression of apoptotic and apoptotic-related genes in pregnancy complications, the involvement of these genes in RPL remains to be elucidated.

TH17/IL23 cytokine gene polymorphisms in bullous pemphigoid.

Background: TH17/IL-23 immune axis is considered to be involved in the pathogenesis of autoimmune and chronic inflammatory diseases. Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease, characterized by the presence of autoantibodies against the components of the dermal-epidermal junction. Animal studies and characterization of patient samples point toward a contribution of TH17 cells in BP pathogenesis.

Association between TH2 Cytokine Gene Polymorphisms and Risk of Bullous Pemphigoid.

Background: T-helper 2 (Th2)-associated cytokines are involved in the pathogenesis of bullous pemphigoid (BP), an autoimmune skin disease. Increased expression of Th2 cytokines such as interleukin-4 (IL-4), IL-5, IL-6, IL-10, and IL-13 have been observed in serum, skin biopsies and/or blister fluid. This study aimed to uncover a possible association between Th2 cytokine genetic variations and susceptibility to BP.

Hsa-miR-27a-3p and epidermal growth factor receptor expression analysis in glioblastoma FFPE samples.

Aim: Glioblastoma multiforme (GBM) is the most invasive type of glial tumors. MicroRNAs as the small, noncoding RNAs have been revealed that play an important role in tumorigenic processes. So, they may be used as potential biomarkers for detection and prognosis of cancers at the early stages.

IL12B and IL23R polymorphisms are associated with alopecia areata.

Alopecia areata is an autoimmune disease in which activation of autoreactive T cells and inflammatory immune signals target the hair follicles autoantigens. Although cytokines are involved in regulating autoimmune inflammation, the specific involvement of these molecules in the pathogenesis of alopecia areata has been remained unsettled. Here, a possible influence of IL12B, IL17A, and IL23R variations on susceptibility to alopecia areata in Iranian patients was investigated.

Overlapping and Distinct Gene Polymorphisms in Alopecia Areata in an Iranian Population.

Alopecia areata (AA) is considered to have a multifactorial etiology and polymorphisms in certain genes have been shown to be associated with AA. Although several reports have investigated the effect of (FASLG) gene variations with predisposing to AA, genetic association of disease, however, varies among different ethnicities and no data have so far been reported in Iranian population. The present study aimed to uncover a possible association between variations in genes and AA.

Altered levels of salivary biochemical markers in periodontitis.

Purpose: To investigate the association between periodontitis and levels of biochemical markers as well as enzyme activity.

Methods: Unstimulated whole saliva samples were obtained from 30 patients with periodontitis. Biochemical factors including the levels of malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), uric acid (UA), and lactoferrin, as well as β-hexosaminidase (β-HEX) activity were measured.

The implication of single-nucleotide polymorphisms in ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is an undesirable complication in the course of ovarian stimulation. This kind of stimulation is aimed at acquiring a sufficient number of high-quality oocytes in in vitro fertilization (IVF). Whereas the predisposition to OHSS could be impacted by genetic polymorphisms in susceptible genes, the present study has been jointly conducted with an Iranian cohort to scrutinize its relevant implication.

Proinflammatory Cytokine Gene Polymorphisms in Bullous Pemphigoid.

Bullous pemphigoid (BP) is a rare autoimmune skin blistering disease, characterized by the presence of autoantibodies against hemidesmosomal autoantigens. Cytokine expression is altered in BP patients, and several of these differently expressed cytokines, including IL-1α, IL-1β, IL-8, and TNF-α, contribute to disease pathogenesis. Since genetic polymorphisms in the genes of these cytokines might be implicated in susceptibility to BP disease, we aimed at testing this implication in susceptibility to BP in an Iranian cohort.

Genetic variant association of PTPN22, CTLA4, IL2RA, as well as HLA frequencies in susceptibility to alopecia areata.

Alopecia areata (AA) is characterized by a genetically complex inheritance. HLA frequencies, as well as the single nucleotide polymorphism (SNP) in PTPN22, CTLA4, and IL2RA genes, have been described to be associated with AA susceptibility. So far, no independent replication of these studies has been reported, and no data exist on a possible association between AA disease and these SNPs or influence of HLA frequencies in Iranian population.

TNF-α -308G/A gene polymorphism in bullous pemphigoid and alopecia areata.

Background: TNF-α -308G/A polymorphism has been investigated in few studies for an association with susceptibility to bullous pemphigoid (BP) and alopecia areata (AA). Yet, these findings had so far not been independently replicated, and no data on a possible association of TNFα -308G/A polymorphism with these diseases in Iranian population were available.

Objectives: In the present study, a possible effect of TNF-α -308G/A variation on susceptibility to BP or AA disease was evaluated.