Autoimmune Inflammatory Disease Research Articles

Association of Anti-Smith, Anti-Ro, and Anti-ribonucleoprotein Combination With Accelerated Development of Lupus Nephritis in Systemic Lupus Erythematosus Patients in Saudi Arabia.

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disorder affecting multiple organs. Lupus nephritis (LN), one of its serious complications, is characterized by proteinuria and renal dysfunction. The objective of this study was to evaluate the association between a specific antibody profile (anti-Smith [anti-Sm], anti-Ro, and anti-ribonucleoprotein [anti-RNP]) and the time to develop LN in SLE patients. A retrospective, single-center cohort study was conducted at King Fahad Medical City (KFMC) in Riyadh, Saudi Arabia, and included 128 patients with LN who visited the Rheumatology Clinic between 2014 and 2021. Patients were divided into two groups: a positive serological profile group, which included patients positive for all three antibodies (anti-Sm, anti-Ro, and anti-RNP), and a negative serological profile group (which included patients with at least one negative antibody result). Data on demographics, antibody profiles, time to proteinuria development, and LN classification were analyzed. The time to develop proteinuria from the initial diagnosis of LN to the first detection of proteinuria exceeding 500 mg was categorized into less than 1 year, 1-5 years, 6-10 years, and more than 10 years. Our findings revealed that a substantial proportion (95%) of patients positive for all three antibodies (anti-Sm, anti-Ro, and anti-RNP) had a significantly higher likelihood of developing proteinuria within the first five years of their SLE diagnosis, compared to 89.66% of patients with a negative serological profile. The findings suggest that the presence of anti-Sm, anti-Ro, and anti-RNP antibodies is associated with a higher risk of early LN development, specifically within five years after initial SLE diagnosis. Regular monitoring and proactive management of high-risk patients can reduce the burden of LN and its complications.

Terminalia bellericia (Gaertn.) Roxb. Fruit Extracts Inhibit the Growth of Bacterial Triggers of Selected Autoimmune Inflammatory Diseases and Potentiate the Activity of Conventional Antibiotics

Terminalia bellericia (Gaertn.) Roxb. Fruit Extracts Inhibit the Growth of Bacterial Triggers of Selected Autoimmune Inflammatory Diseases and Potentiate the Activity of Conventional Antibiotics

Assessment of the Expression Levels of USP27X and DDX3X genes in Systemic Lupus Erythematosus (SLE) Patients

Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease influencing numerus tissues in body. Ubiquitin carboxyl-terminal hydrolase 27 (USP27X) is a deubiquitinating enzyme involved in the type I interferons (IFNs) generation, apoptosis and production of proinflammatory mediators. DEAD-box helicase 3 X-linked (DDX3X) is a ribonucleic acid (RNA) helicases and contributes to the generation of type I IFNs, and proinflammatory mediators. Considering the involvement of IFN type I, apoptotic cell death and proinflammatory mediators in the pathogenesis of SLE, the expression levels of USP27X and DDX3X genes were assessed in SLE patients. Methods: Two groups, including SLE patients and healthy subjects, were included in the study and the expression levels of USP27X and DDX3X genes in their peripheral blood mononuclear cells (PBMC) were quantified by the real-time polymerase chain reaction (PCR). Results: The results demonstrated the expression level of DDX3X gene was 5.9-fold higher in the SLE patients compared to the healthy subjects ( P < .01). No significant difference in the expression level of USP27X gene was detected between both groups ( P > .05). Conclusion: A significant elevation in the level of DDX3X gene in SLE patients prepossess the potential involvement of DDX3X in SLE pathogenesis possibly through the induction of proinflammatory mediators. In spite of the potential involvement of USP27X in SLE through the induction of type 1 IFNs, and apoptotic cell death, our finding did not provide evidence in the contribution of USP27X in SLE pathogenesis.

Magnesium Supplementation Modifies Arthritis Synovial and Splenic Transcriptomic Signatures Including Ferroptosis and Cell Senescence Biological Pathways

Background: Rheumatoid arthritis (RA) is a common systemic autoimmune inflammatory disease that can cause joint damage. We have recently reported that oral magnesium supplementation significantly reduces disease severity and joint damage in models of RA. Methods: In the present study, we analyzed the transcriptome of spleens and synovial tissues obtained from mice with KRN serum-induced arthritis (KSIA) consuming either a high Mg supplemented diet (Mg2800; n = 7) or a normal diet (Mg500; n = 7). Tissues were collected at the end of a 15-day KSIA experiment. RNA was extracted and used for sequencing and analyses. Results: There was an enrichment of differentially expressed genes (DEGs) belonging to Reactome and Gene Ontology (GO) pathways implicated in RA pathogenesis such as RHO GTPases, the RUNX1 pathway, oxidative stress-induced senescence, and the senescence-associated secretory phenotype. Actc1 and Nr4a3 were among the genes with the highest expression, while Krt79 and Ffar2 were among the genes with the lowest expression in synovial tissues of the Mg2800 group compared with the Mg500 group. Spleens had an enrichment for the metabolism of folate and pterines and the HSP90 chaperone cycle for the steroid hormone receptor. Conclusions: We describe the tissue transcriptomic consequences of arthritis-protecting Mg supplementation in KSIA mice. These results show that oral Mg supplementation may interfere with the response to oxidative stress and senescence and other processes known to participate in RA pathogenesis. We provide new evidence supporting the disease-suppressing effect of increased Mg intake in arthritis and its potential to become a new addition to the therapeutic options for RA and other autoimmune and inflammatory diseases.

Emerging Role of NAT10 as ac4C Writer in Inflammatory Diseases: Mechanisms and Therapeutic Applications.

The incidence of inflammatory diseases, including infections, autoimmune disorders, and tumors, is consistently increasing year by year, posing a significant and growing threat to human health on a global scale. Recent research has indicated that RNA acetylation modification, a specific type of post-transcriptional modification, may play a critical role in the pathogenesis of these diseases. Among the various mechanisms of RNA modification, N-acetyltransferase 10 (NAT10) has been identified as the sole cytidine acetyltransferase in eukaryotes. NAT10 is responsible for acetylating mRNA cytosine, which leads to the formation of N4-acetylcytidine (ac4C), a modification that subsequently influences mRNA stability and translation efficiency. Despite these insights, the specific roles and underlying mechanisms by which RNA acetylation contributes to the onset and progression of inflammatory diseases remain largely unclear. This review aimed to elucidate the alterations in NAT10 expression, the modifications it induces in target genes, and its overall contribution to the pathogenesis of various inflammatory conditions. It has been observed that NAT10 expression tends to increase in most inflammatory conditions, thereby affecting the expression and function of target genes through the formation of ac4C. Furthermore, inhibitors targeting NAT10 present promising therapeutic avenues for treating inflammatory diseases by selectively blocking NAT10 activity, thereby preventing the modification of target genes and suppressing immune cell activation and inflammatory responses. This potential for therapeutic intervention underscores the critical importance of further research on NAT10's role in inflammatory disease pathogenesis, as understanding these mechanisms could lead to significant advancements in treatment strategies, potentially transforming the therapeutic landscape for these conditions.

Quantitative susceptibility mapping of the fear circuit: Associations with silent symptoms in relapsing-remitting multiple sclerosis.

Background: Multiple sclerosis (MS) is a long-term autoimmune inflammatory disorder that affects the central nervous system leading to neurodegeneration, and can involve a variety of symptoms. These symptoms can include fatigue, anxiety, depression, and cognitive decline, which may be silent. The objective of this study was to explore changes in brain iron deposition in people with relapsing-remitting MS (pw-RRMS) compared to healthy controls (HCs), with a particular focus on regions of fear circuit. Additionally, the study aimed to evaluate relationship between iron deposition in these areas and clinical measurements. Methods: Pw-RRMS and HCs participants underwent brain MRI scans using quantitative susceptibility mapping (QSM) to assess iron deposition in the fear circuit between the two groups. The study analyzed correlations between brain susceptibility changes and clinical measurements. Results: We recruited 35 pw-RRMS (mean age = 46.7 ± 11years; median EDSS = 2.5) and 18 HCs (mean age = 40.6 ± 17.8years). Our research revealed significant increases in QSM signals relating to iron deposition in pw-RRMS compared to HCs, whole fear circuit (β = 5.82, p < 0.001), caudate (β = 21.48, p < 0.001), and putamen (β = 17.53, p = 0.03), showing the greatest difference. The whole fear circuit and particularly the caudate are strongly associated with fatigue in pw-RRMS. QSM values in the anterior cingulate cortex significantly differed between pw-RRMS with normal and abnormal depression scores (p = 0.007). Conclusions: These results strengthen the relationship between increased iron deposition in fear circuit regions and specific silent symptoms in pw-RRMS. However, further studies are required to confirm these findings and clarify the implications of iron accumulation in MS pathophysiology.

PTPN22 and the pathogenesis of ulcerative colitis: Insights into T cell differentiation and the JAK/STAT signaling pathway

70 % of the ulcerative colitis (UC) linked gene loci are associated with other autoimmune or immunodeficient diseases. The phosphatase activity of PTPN22 can regulate the development of T cells and contribute to regulate the level of inflammation in autoimmune diseases. We produced PTPN22-CS thymus-specific transgenic mice, which suppressed PTPN22 enzyme activity in the thymocytes. Overexpressed PTPN22-CS facilitated the development of the thymocytes towards CD4+T cells and resulted in an increased proportion of the Th1 and Treg cells in the UC mesenteric lymph nodes. PTPN22-CS promoted the activation of the JAK/STAT signaling pathway in the Th1 and Treg cells that localized in the colon, resulting in an excessive production of inflammatory mediators such as IL-2 and IFN-γ. Consequently, PTPN22-CS contributes to the inflammatory response of ulcerative colitis. In summary, the tyrosine phosphatase activity of PTPN22 plays a role in modulating UC by regulating T cell differentiation and modulating the JAK/STAT signaling pathway, thereby influencing the inflammatory response in colonic. These findings provide new insight into the association between PTPN22 and the pathogenesis of UC.

Perioperative Considerations for Hip Arthroplasty in Patients with Rheumatoid Arthritis.

Due to its distinct features, rheumatoid arthritis (RA), an inflammatory autoimmune disorder, poses challenges in planning for surgical interventions. This review includes available evidence regarding perioperative considerations in management of RA patients, with a focus on hip surgery. RA can affect multiple joints, with development of extra-articular manifestations; therefore, preoperatively, comprehensive medical assessments, including cardiovascular or pulmonary evaluation must be considered in addition to surgical considerations. Modification of medications capable of controlling RA-related disease activity is critical, and requires collaboration with rheumatologists. Surgical considerations include the choice of surgical approach, implant selection, and problems related to weakened soft tissues, fragile bone density, and bony deformity such as protrusio acetabuli. Careful monitoring and more active rehabilitation are recommended for RA patients due to higher risk of postoperative complications. For achievement of optimal outcomes, use of a multidisciplinary perioperative approach is required for patients with RA.

Role of innate immune receptors in the psoriasis development

Psoriasis is an immune-mediated autoimmune inflammatory skin disease with a prevalence of 2 to 3% worldwide. In the psoriasis development and pathogenesis an important role is played by disorders in the immune system. Disruption of the innate and adaptive immune response mechanisms with the involvement of keratinocytes leads to the initiation and maintenance of inflammation. Immune reactions are activated in the skin, in which various cells participate (macrophages, dendritic cells, mast cells, innate immune lymphoid cells, melanocytes, keratinocytes, Langerhans cells and γδT cells; T and B cells; epithelial endothelial and stromal cells of the skin), each of which expresses pattern recognition receptors that respond to pathogens and cell damage itself. Many of these receptors, in particular toll-like receptors and NOD-like receptors play an important role in the pathogenesis of psoriasis. The associated innate receptors signaling cascades that activate in the skin cells may become potential targets for the treatment of this disease. To date, there are several approved drugs for biological therapy of psoriasis. The study of the role of the innate immune cells receptors in inflammatory skin pathologies requires further exploration and new developments.

The Anti-Inflammatory Roles of Vitamin D for Improving Human Health

Vitamin D receptors (VDRs) are present in almost all cells of the immune system, including B cells, T cells, NK (Natural Killer) cells, dendritic cells, and monocytes, as well as the epithelial cells of many organs such as the intestine, pancreas, prostate, lungs, and cardiomyocytes. In addition, some immune cells, including dendritic cells, macrophages, and B and T cells, can synthesize calcitriol by expressing 1α-hydroxylase. Upon binding to VDRs, vitamin D (Vit D) regulates the expression of genes involved in immune responses, including those encoding for cytokines. It modulates the production of pro-inflammatory cytokines while promoting the synthesis of anti-inflammatory cytokines. Vit D also affects the differentiation and maturation of cells of the immune system. By inhibiting the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, Vit D reduces the expression of pro-inflammatory genes. These effects highlight the potential of Vit D as a therapeutic agent in the management of inflammatory diseases, including autoimmune disorders, cardiovascular diseases, diabetes, metabolic syndrome, cancer, neurological diseases, depression, and inflammatory bowel disease.

Promotion of TLR7-MyD88-dependent inflammation and autoimmunity in mice through stem-loop changes in Lnc-Atg16l1

Uncontrolled TLR signaling can cause inflammatory immunopathology and trigger autoimmune diseases. For example, TLR7 promotes pathogenesis of systemic lupus erythematosus. However, whether RNA structural changes affect nucleic acids-sensing TLRs signaling and impact disease progression is unclear. Here by iCLIP-seq we identify a TLR7-binding long non-coding RNA, Lnc-Atg16l1, and find that it promotes TLR7 and other MyD88-dependent TLRs signaling in various types of immune cells. Depletion of Lnc-Atg16l1 attenuates development of TLR7-linked autoimmune phenotypes in the mouse SLE model. Mechanistically, we find that Lnc-Atg16l1 binds to TLR7 at bases near U84 and MyD88 at bases around A129. The analysis of Lnc-Atg16l1 in situ structures show that it strengthens the interaction between TIR domain of TLR7 and MyD88 through specific stem-loop structure changes as a molecular scaffold after TLR7 activation to promote TLR7 downstream signaling. Therefore, we discover a mechanism for host RNA regulation of innate signaling and autoimmune disease through its structural changes. These findings provide insights into the pro-inflammatory function of self RNA in a structure-dependent manner and suggest a potential target for TLR-related autoimmune disorders.

Therapeutic efficacy of brown propolis fromAraucaria sp.in modulating rheumatoid arthritis.

Rheumatoid arthritis is a systemic inflammatory autoimmune disease with prevalence estimated at 0.5% to 1% of the population. As one of the treatment routes of rheumatoid arthritis is based on the use of nonsteroidal anti-inflammatory drugs, the use of natural products with anti-inflammatory potential becomes relevant. Brown propolis has several biological properties, including immunomodulatory and anti-inflammatory effects. Thus, the present study evaluated the therapeutic efficacy of the crude extract of brown propolis from Araucaria sp. through experimental models of analgesia, anti-inflammatory activity, and rheumatoid arthritis. Hyperalgesia was evaluated by mechanical and thermal sensitivity. Anti-inflammatory activity was evaluated by plantar volume, cell migration and NF-kB expression in carrageenan-induced paw oedema. In collagen-induced rheumatoid arthritis, it was evaluated by mechanical and thermal nociception on the plantar surface, and mechanical nociception in the femorotibial and caudal joints, evaluation of plantar volume, radiography, weight gain and biochemical profile. The results demonstrated that the oral administration of brown propolis can modulate the course of rheumatoid arthritis, and it can inhibit pain through the modulation of mechanical sensitivity. The anti-arthritic effect of propolis may be due to its anti-inflammatory capacity, which includes inhibiting oedema formation, cell migration, and NF-kB expression, as well as preserving joint space and normalizing urea levels. This was an animal model study. Therefore, brown propolis should be evaluated in studies of human RA to determine efficacy.

Trained Mesenchymal Stromal Cell-Based Therapy HXB-319 for Treating Diffuse Alveolar Hemorrhage in a Pristane-induced Murine Model.

Mesenchymal stromal cells (MSCs) can modulate immune responses and suppress inflammation in autoimmune diseases. Although their safety has been established in clinical trials, the efficacy of MSCs is inconsistent due to variability in potency among different preparations and limited specificity in targeting mechanisms driving autoimmune diseases. We utilized High-Dimensional Design of Experiments methodology to identify factor combinations that modulate gene expression by MSCs to mitigate inflammation. This led to a novel MSC-based cell therapy, HXB-319. Its anti-inflammatory properties were validated in vitro by flow cytometry, RT-PCR, and mass spectrophotometry. To evaluate in vivo efficacy, we treated a diffuse alveolar hemorrhage (DAH) mouse model (C57Bl/6). Seven days post-DAH induction with pristane, mice received either MSCs or HXB-319 (2X106 cells, IP). On day 14, peritoneal lavage fluid (PLF) and lung tissue were collected for flow cytometry, histopathological examination and mRNA. HXB-319 increased gene expression levels of anti-inflammatory, angiogenic and anti-fibrotic factors (e.g. TSG-6, VEGF and HGF). KEGG pathway analysis confirmed significant activation of relevant anti-inflammatory, angiogenic, and anti-fibrotic proteins, corroborating RT-PCR results.In the DAH model, HXB-319 significantly reduced lung inflammation and alveolar hemorrhage compared to MSC treated and untreated DAH mice. HXB-319 treatment also significantly decreased neutrophils, plasmacytoid dendritic cells and RORγT cells, and increased FoxP3+ cells in PLF, and reversed alterations in mRNA encoding IL-6, IL-10 and TSG-6 in lung tissue compared to DAH mice. HXB-319 effectively controls inflammation and prevents tissue damage in pristane induced DAH, highlighting its therapeutic potential for autoimmune inflammatory diseases.

NF-κB Signaling Pathway in Rheumatoid Arthritis: Mechanisms and Therapeutic Potential.

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease that imposes a heavy economic burden on patients and society. Bone and cartilage destruction is considered an important factor leading to RA, and inflammation, oxidative stress, and mitochondrial dysfunction are closely related to bone erosion and cartilage destruction in RA. Currently, there are limitations in the clinical treatment methods for RA, which urgently necessitates finding new effective treatments for patients. Nuclear transcription factor-κB (NF-κB) is a signaling transcription factor that is widely present in various cells. It plays an important role as a stress source in the cellular environment and regulates gene expression in processes such as immunity, inflammation, cell proliferation, and apoptosis. NF-κB has long been recognized as a pathogenic factor of RA, and its activation can exacerbate RA by promoting inflammation, oxidative stress, mitochondrial dysfunction, and bone destruction. Conversely, inhibiting the activity of the NF-κB pathway effectively inhibits these pathological processes, thereby alleviating RA. Therefore, NF-κB may be a potential therapeutic target for RA. This article describes the physiological structure of NF-κB and its important role in RA through the regulation of oxidative stress, inflammatory response, mitochondrial function, and bone destruction. Meanwhile, we also summarized the impact of NF-κB crosstalk with other signaling pathways on RA and the effect of related drugs or inhibitors targeting NF-κB on RA. The purpose of this article is to provide evidence for the role of NF-κB in RA and to emphasize its significant role in RA by elucidating the mechanisms, so as to provide a theoretical basis for targeting the NF-κB pathway as a treatment for RA.

IL-37 suppresses CNS autoimmunity by increasing the frequency of Treg cells and reducing CD4 + T cell-derived IL-10 production.

Interleukin-37 (IL-37) has anti-inflammatory properties in innate and adaptive immunity. Patients with multiple sclerosis (MS), an autoimmune inflammatory demyelinating disease of the central nervous system (CNS), have increased serum levels of IL-37. However, it is unknown whether IL-37 has an inhibitory effect on ongoing autoimmune neuroinflammation, thus offering a potential MS therapy. Here, we examined the effect of IL-37 in an experimental autoimmune encephalomyelitis (EAE) model after disease onset to determine if it was protective. IL-37-treated mice developed a less severe disease than control mice, with reduced demyelination as determined by increased expression of myelin basic protein. IL-37 suppressed inflammation by decreasing infiltration of CD4 + T cells into the CNS and increasing the frequency of regulatory T cells, while IL-10 expression by CD4 + T cells decreased over time in the CNS. Our findings confirm the immunomodulatory role of IL-37 in CNS inflammation during ongoing disease, thus indicating the potential of IL-37 as an inhibitory reagent for MS therapy.

Immunomodulatory effects of HYCO-3, a dual action CO-releaser/Nrf2 activator.

HYCOs are hybrid molecules consisting of activators of the transcription factor Nrf2 conjugated to carbon monoxide (CO)-releasing moieties. These "dual action" compounds have been designed to mimic the activity of heme oxygenase-1 (HO-1), a stress inducible cytoprotective enzyme that degrades heme to CO which expression is regulated by Nrf2. HYCOs have recently shown efficacy in ameliorating experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. However, the mechanism(s) of action of HYCOs still remain to be fully investigated. Here, we assessed the effects of HYCO-3, a prototype of these hybrids, on myeloid-derived cells, microglial cells and T lymphocytes obtained from EAE-immunized mice. HYCO-3 exerted immunomodulatory effects on all the examined cell populations by inhibiting the generation of pro-inflammatory cytokines and nitric oxide, and downregulating antigen-presenting capacity of these cells. The observed effects support the view that HYCOs are promising candidates to be developed for the treatment of autoimmune and chronic inflammatory disorders.

Impact of Gut Microbiota on the Development of Diseases

Aim: The aim of this article is to review the latest scientific research on the influence of intestinal microbiota on the development of diseases. In this article we will discuss the importance of the intestinal microbiota, the differences in the composition of the microbiota between healthy and sick people and the relationship between the intestinal microbiota and metabolic, inflammatory, cardiovascular and neurodegenerative diseases. Abbreviated description of the state of knowledge: The gut microbiota plays a key role in human health by influencing the development and progression of various diseases. Numerous studies have shown that an imbalance in gut microbiota, called dysbiosis, may be linked to a number of conditions. Intestinal microflora interacts with the immune system, modulates inflammation and influences metabolic pathways, which emphasizes its importance in the development of diseases. Conclusions: Intestinal microflora is crucial to health, regulating immune, metabolic and neurological functions. Dysbiosis, i.e. disturbance of the balance of intestinal microflora, is associated with diseases such as type 2 diabetes, obesity, inflammatory bowel diseases, allergies, autoimmune diseases and neuropsychiatric disorders. Healthy microflora, influenced by diet, pH and nutrients, are essential for metabolism, immune system regulation and neuronal communication. Recently, scientists have become interested in the possibility of using this knowledge in treatment. Appropriate dietary management, probiotic supplementation and fecal microflora transplantation show promising potential. Future research should focus on elucidating the specific mechanisms by which the gut microbiota influences disease processes and developing targeted therapies to exploit the therapeutic potential of the microbiota.

Development of a Panel of Biomarkers for Differential Diagnosis of Multiple Sclerosis.

Demyelinating diseases are a group of heterogeneous pathologies that affect the nervous system and reduce the quality of life. One of such diseases is multiple sclerosis (MS), an inflammatory autoimmune neurodegenerative disease of the central nervous system (CNS). At the initial stages, MS can mimic some infectious, neoplastic, genetic, metabolic, vascular, and other pathologies. Accurate differential diagnosis of this disease is important to improve the quality of life of patients and reduce possible irreversible damage to the central nervous system. In this work, we confirmed the possibility of using our previously proposed candidate panel of MS biomarkers to distinguish MS from neuromyelitis optica spectrum disorder (NMOSD) and amyotrophic lateral sclerosis (ALS). We have shown that our proposed panel (SPTAN1601-644 + PRX451-494 + PTK6301-344 + LMP1285-330) allows us to distinguish MS from ALS (AUC = 0.796) and NMOSD (AUC = 0.779).

Gut dysbiosis mediates the association between antibiotic exposure and chronic disease.

Antibiotics are safe, effective drugs and continue to save millions of lives and prevent long-term illness worldwide. A large body of epidemiological, interventional and experimental evidence shows that exposure to antibiotics has long-term negative effects on human health. We reviewed the literature data on the links between antibiotic exposure, gut dysbiosis, and chronic disease (notably with regard to the "developmental origins of health and disease" ("DOHaD") approach). Molecular biology studies show that the systemic administration of antibiotic to infants has a rapid onset but also often a long-lasting impact on the microbial composition of the gut. Along with other environmental factors (e.g., an unhealthy "Western" diet and sedentary behavior), antibiotics induce gut dysbiosis, which can be defined as the disruption of a previously stable, functionally complete microbiota. Gut dysbiosis many harmful long-term effects on health. Associations between early-life exposure to antibiotics have been reported for chronic diseases, including inflammatory bowel disease, celiac disease, some cancers, metabolic diseases (obesity and type 2 diabetes), allergic diseases, autoimmune disorders, atherosclerosis, arthritis, and neurodevelopmental, neurodegenerative and other neurological diseases. In mechanistic terms, gut dysbiosis influences chronic disease through direct effects on mucosal immune and inflammatory pathways, plus a wide array of direct or indirect effects of short-chain fatty acids, the enteric nervous system, peristaltic motility, the production of hormones and neurotransmitters, and the loss of intestinal barrier integrity (notably with leakage of the pro-inflammatory endotoxin lipopolysaccharide into the circulation). To mitigate dysbiosis, the administration of probiotics in patients with chronic disease is often (but not always) associated with positive effects on clinical markers (e.g., disease scores) and biomarkers of inflammation and immune activation. Meta-analyses are complicated by differences in probiotic composition, dose level, and treatment duration, and large, randomized, controlled clinical trials are lacking in many disease areas. In view of the critical importance of deciding whether or not to prescribe antibiotics (especially to children), we suggest that the DOHaD concept can be logically extended to "gastrointestinal origins of health and disease" ("GOHaD") or even "microbiotic origins of health and disease" ("MOHaD").

Collagen triple helix repeat-containing 1 protein: an emerging biomarker and its influence on the clinical and sonographic disease severity in Egyptian medicated female rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of synovial joints, with a multifactorial etiology. Collagen triple helix repeat-containing 1 protein (CTHRC1) is a biomarker produced by fibroblast-like synoviocytes, which was shown to be highly expressed in RA patients. The study aimed to measure serum CTHRC1 level in female RA patients currently on medical treatment and its influence on the clinical and sonographic severity of the disease.ResultsThe patients’ mean age was 43.39 ± 8.55 years and median RA disease duration of 5.5 (0.33–20) years. RA patients showed significantly higher serum CTHRC1 level [89.71 ng/ml (53.95–353.45)] in comparison to controls [87.38 ng/ml (44.47–110.3)] (U = 430, P = 0.014). Furthermore, higher serum CTHRC1 levels were recorded in seropositive versus seronegative patients (U = 76, P = 0.022) and in RA patients with severe disease activity compared to those with lower disease activity (H = 9.79, P = 0.007). Furthermore, serum CTHRC1 levels were lower in RA patients receiving biological therapy compared to those receiving conventional therapy; however, this difference did not reach statistical significance.Significant positive correlations were found between CTHRC1 and disease activity, acute-phase reactants, serological markers, functional assessment, fatigue, and erosions detected by ultrasound, while a significant negative correlation was recorded between CTHRC1 and duration of biologic intake (rs = − 0.45, P = 0.036). Furthermore, on multivariate linear regression analysis, serum CTHRC1 was the only significant predictor for higher disease activity (P = 0.028, B = 0.009, 95% CI 0.001 to 0.017).ConclusionRA patients showed higher CTHRC1 serum levels compared to healthy controls, especially those with seropositivity and highly active disease. Furthermore, it was positively associated with poor patient functional outcome, fatigability, and erosive findings by ultrasound, thus suggesting that serum CTHRC1 can be a good predictor for high RA disease activity and possibly severity. Moreover, biological therapy could influence serum CTHRC1 levels in these patients.