Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
30572137 Novel Sjögren's autoantibodies found in fibromyalgia patients with sicca and/or xerostomi 2019 Feb INTRODUCTION: A significant proportion of patients with fibromyalgia (FM) complain of dry eyes and mouth. Many Sjögren's syndrome (SS) patients also complain of FM symptoms, and there is literature that suggests that there is interplay between these two disorders. Recently, the presence of novel tissue specific autoantibodies (TSAs), SP-1, CA6, and PSP, has been observed in the early stages of SS. These early markers present themselves before the classic autoantibodies, such as SS-A/Ro, SS-B/La, ANA, and RF. OBJECTIVE: This study aims to examine the relationship between SS and FM by testing patients with FM who also complain of xerostomia and sicca symptoms, for SS- related biomarkers. METHODS: A cohort of 185 patients who met both the 1990 and 2010 preliminary diagnostic criteria for FM and who admitted to symptoms of sicca and/or xerostomia were selected for this study. Serum from 151 study patients was sent to a tertiary lab, Immco Diagnostics, for testing of the classic autoantibodies (SS-A/Ro, SS-B/La, ANA and RF) and TSAs (SP-1, CA6, PSP), while the rest (34 patients) were tested for TSAs only. RESULTS: Of the 151 patients who were evaluated for both the early and classic SS markers, 49 (32%) tested positive for SS autoantibodies. Of those, 4 (3%) tested positive for the classic SS markers only, 40 (26%) of the patients tested positive for the early SS markers only, and 5 (3%) tested positive for both the early and classic SS markers. Of the 34 patients who were tested for early SS markers only, 10 (29%) tested positive and 24 (71%) tested negative. Further analysis of all the patients that tested positive for the TSAs (n = 55), found 83.6% (46) were positive for SP-1, 12.7% (7) were positive for CA6 and 20.0% (11) were positive for PSP. 85.5% (47) of these patients were positive for only one of the TSAs and 14.5% (8) were positive for more than one TSA. CONCLUSION: Approximately 1/3 of FM patients that were tested for both the TSAs and classic Sjögren's markers tested positive for a SS biomarker, and the majority of those patients tested positive for one or more of the TSAs. This suggests that autoimmunity, specifically early- stage Sjögren's syndrome, may be involved in the pathophysiology of fibromyalgia.
31762886 Adult Still's disease and squamous cell carcinoma in a 69-year-old woman. 2019 Adult-onset Still's disease (AOSD) has been recognized as a cause of fevers of unknown origin. Malignancies are the most important differential diagnoses of AOSD which has been rarely reported in association with cancer. The present paper undertakes the study of a 69-year-old Tunisian woman with AOSD according to the diagnostic criteria of Yamaguchi. She was treated by prednisone, then associated with methotrexate. 18 months later, she developed a squamous cell carcinoma treated with chemotherapy and radiotherapy.
31391399 Acquired Amegakaryocytic Thrombocytopenia in Adult-onset Still's Disease: Successful Combi 2019 Dec 1 Adult-onset Still's disease (AOSD) sometimes demonstrates hematologic disorder, whereas acquired amegakaryocytic thrombocytopenia (AAT) involvement is extremely rare. We herein report a 67-year-old woman with relapse of AOSD who concomitantly developed AAT. Thrombocytopenia along with high disease activity of AOSD was resistant to high-dose prednisolone, even in combination with methotrexate and tacrolimus. However, alternative treatment with cyclosporine after administering tocilizumab resulted in the improvement of thrombocytopenia, ultimately demonstrating that combination therapy based on suppressing the intractable disease activity of AOSD and subsequently adding a reliable immunosuppressant was required to achieve remission.
31172803 The function of ncRNAs in rheumatic diseases. 2019 May Rheumatic diseases are a group of chronic heterogeneous autoimmune disorders characterized by abnormal regulation of the innate and adaptive immune systems. Despite extensive efforts, the full spectrum of molecular factors that contribute to the pathogenesis of rheumatic diseases remains unclear. ncRNAs can govern gene expression at the transcriptional and post-transcriptional levels in multiple diseases. Recent studies have demonstrated an important role for ncRNAs, such as miRNAs and lncRNAs, in the development of immune cells and rheumatic diseases. Here, we focus on the epigenetic regulatory roles of ncRNAs in the pathogenesis of rheumatic diseases and as biomarkers of disease state.
31745741 Myocarditis in Adult-Onset Still's Disease: Case-Based Review. 2020 Mar Cardiac involvement in adult-onset Still's disease (AOSD) usually manifests as a pericardial disease. Myocarditis is uncommon (prevalence of 7%). However, the cardiocirculatory failure is the second cause of life-threatening AOSD. Herein, we report the case of a 38-year-old man who was diagnosed with myocarditis caused by AOSD. He was treated medically with steroids and methotrexate, and his course was favorable. A literature search in PubMed/MEDLINE and Scopus databases from 1971 to 2019 identified 47 additional cases of myocarditis and AOSD. The main features found in these reports were reviewed and are the following: (i) myocarditis is a rare complication of AOSD manifested by fever, chest pain, dyspnea, and tachycardia; (ii) cardiac biomarkers, electrocardiogram (ECG), transthroracic echocardiography (ECHO), and cardiac magnetic resonance imaging (MRI) are useful noninvasive diagnostic tools; and (iii) myocarditis is a potentially life-threatening complication of AOSD but responds positively to steroids and other immunomodulatory drugs. This review suggests that this entity should be suspected in cases of acute febrile myocarditis after ruling out other causes since a prompt treatment results in a good prognosis.
31256671 High re-operation and complication rates 11 years after arthrodesis of the wrist for non-i 2019 Jul AIMS: Plate and screw fixation has been the standard treatment for painful conditions of the wrist in non-rheumatoid patients in recent decades. We investigated the complications, re-operations, and final outcome in a consecutive series of patients who underwent wrist arthrodesis for non-inflammatory arthritis. PATIENTS AND METHODS: A total of 76 patients, including 53 men and 23 women, with a mean age of 50 years (21 to 79) underwent wrist arthrodesis. Complications and re-operations were recorded. At a mean follow-up of 11 years (2 to 18), 63 patients completed questionnaires, and 57 attended for clinical and radiological assessment. RESULTS: Of the 76 patients, 46 (60.5%) had complications, resulting in 65 re-operations, mainly related to the plate and screws. In the 63 patients who completed the questionnaires, the mean Quick Disabilities of Arm, Shoulder and Hand (QuickDASH) score was 36 (0 to 91), the mean Patient-Rated Wrist and Hand Evaluation (PRWHE) score was 40 (0 to 96), and 14 patients (22%) reported no wrist pain. Grip strength, pinch strength, and pronation and supination were significantly reduced compared with the contralateral forearm. The outcome was worse in patients who had previously undergone surgery to the wrist, and those with complications. A total of 13 are awaiting further re-operations, giving a total re-operation rate of 63% (40/63). CONCLUSION: We observed complications and re-operations throughout the follow-up period and therefore consider wrist arthrodesis to be more complicated than previously assumed. Many of the patients never got used to or accepted their stiff wrists and reported a substantial reduction in function and residual pain. Motion-sparing surgery should be offered prior to wrist arthrodesis. Cite this article: Bone Joint J 2019;101-B:852-859.
32565921 Indications and outcomes of radial head excision: A systematic review. 2020 Jun BACKGROUND: Radial head excision has historically been a common surgical procedure for the operative management of radial head fractures and post-traumatic conditions. With recent advances in other surgical techniques, controversy exists regarding its indications. This review evaluates the indications and outcomes of radial head excision in traumatic and non-traumatic elbow pathology. METHODS: Multiple databases were searched for studies involving radial head excision. Screening and data abstraction were conducted in duplicate. Only studies reporting outcomes for radial head excision were included. RESULTS: Twenty-seven studies with 774 radial head excision patients were included. The most common indications involved acute excision of comminuted radial head fractures (n = 347) and rheumatoid arthritis (n = 201). Post-operative functional scores after acute excision were reported to be good to excellent. In the chronic setting of rheumatoid disease, radial head excision resulted in improved range of motion, although pain was not effectively relieved. DISCUSSION: Outcomes of radial head excision for acute fracture are good to excellent; however, it should not be performed when concurrent or ligamentous injuries are present. Although some studies compared excision to open reduction and internal fixation or replacement, more data are needed to make proper conclusions. The strength of these conclusions is limited by the quality of included literature.
33907622 Venting issues. 2021 Introduction: A 65-year-old woman with type 3 intestinal failure secondary to scleroderma of the gut (limited cutaneous sclerosis (centromere positive) and rheumatoid arthritis (anti-cyclic citrullinated peptide (CCP) and rheumatoid factor positive)) on home parenteral nutrition since 2011 underwent a venting PEG replacement in 2015 for intractable vomiting due to gut dysmotility and small bowel bacterial overgrowth, poorly responding to cyclical antibiotics. An endoscopy was undertaken for planned PEG review for consideration of elective replacement (figure 1).Figure 1Initial endoscopy.Based on this endoscopy, her case was discussed at a multidisciplinary team meeting and the anaesthetic risk of laparotomy to remove the PEG was deemed too high (previous endoscopic PEG exchange under sedation had been poorly tolerated due to tube removal through the oesophagus (possibly affected by scleroderma), and necessitated anaesthesia). Therefore, it was decided to insert a new venting PEG endoscopically alongside the previous buried PEG (cut short and clamped) with the plan to remove the old one at a later date. QUESTIONS: What is shown during the initial endoscopy?What is shown during follow-up endoscopy?
30747500 Inhibition of Interleukin-1β Signaling by Anakinra Demonstrates a Critical Role of Bone L 2019 Jul OBJECTIVE: Arthritogenic alphaviruses, such as Ross River virus (RRV) and chikungunya virus (CHIKV), particularly affect joints of the extremities and can lead to debilitating and potentially chronic polyarthritis/polyarthralgia. The innate immune response of the host plays a crucial role in inducing proinflammatory host factors, leading to tissue destruction and bone loss in the joints. This study was performed to assess how the inhibition of interleukin-1β (IL-1β) signaling using the clinical rheumatoid arthritis drug anakinra influences bone loss in mice with arthritogenic alphavirus infections. METHODS: Mice (n = 5 per group) were infected with RRV or CHIKV and then treated with anakinra. Weight gain and disease severity were measured, tissue viral titers were determined, and histologic changes in joint tissues were assessed. RESULTS: Anakinra therapy reduced RRV- and CHIKV-induced bone loss in this murine model (P < 0.001 and P < 0.05, respectively). Histologic analysis of the knee joint showed that treatment with anakinra decreased epiphyseal growth plate thinning, loss of epiphyseal bone volume, and osteoclastogenesis in the tibia. Importantly, pharmacologic IL-1 receptor (IL-1R) blockade did not improve other clinical features, including disease score, weight loss, or viremia. CONCLUSION: The present findings suggest that anakinra therapy may reduce bone loss in experimental murine models of RRV and CHIKV. Further investigations are needed to assess the potential therapeutic benefits of anakinra in patients with arthritogenic alphavirus disease.
30779858 Fra1 Controls Rheumatoid Factor Autoantibody Production by Bone Marrow Plasma Cells and th 2019 Jul Next to proinflammatory cytokines, autoimmunity has been identified as a key trigger for osteoclast activation and bone loss. IgG-rheumatoid factor (IgG-RF) immune complexes, which are present in patients with rheumatoid arthritis, were shown to boost osteoclast differentiation. To date, the regulation of IgG-RF production in the absence of inflammatory triggers is unknown. Herein, we describe Fra1 as a key checkpoint that controls IgG-RF production by plasma cells and regulates autoimmune-mediated bone loss. Fra1 deficiency in B cells (Fra1(ΔBcell) ) led to increased IgG1-producing bone marrow plasma cells, enhanced IgG-RF production, and increased bone loss associated with elevated osteoclast numbers after immunization. The effect of IgG-RF on osteoclasts in vitro and on osteoclasts associated with bone loss in vivo was dependent on FcγR, especially FcγR3. Furthermore, immunization of WT mice with T-cell-dependent antigens induced a significant and robust decrease in Fra1 expression in bone marrow B cells, which was followed by increased IgG1 production and the induction of osteoclast-mediated bone loss. Overall, these data identify Fra1 as a key mediator of IgG-RF production and autoimmune-mediated bone loss. © 2019 American Society for Bone and Mineral Research.
30338656 Prevalence and predictive value of high-positive rheumatoid factor and anti-citrullinated 2019 Jan AIM: In order to increase diagnostic sensitivity for early disease in rheumatoid arthritis (RA), new classification criteria were approved in 2010 by the American College of Rheumatology and the European League Against Rheumatism. One of the criteria, a high-positive rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA) level, was given a high score of 3. However, the increased prevalence of RF in patients with chronic hepatitis C virus (HCV) infection markedly diminishes the diagnostic specificity of serum RF for RA in these patients. There are no published data on the prevalence and predictive value of high-positive RF and ACPA; thus, we investigated high-positive RF and ACPA levels in nonarthritic patients with chronic HCV infection. METHOD: Anti-citrullinated protein antibody and total RF were determined in serum from nonarthritic patients with chronic HCV infection (all had HCV RNA viremia). RESULT: In 271 HCV-infected patients, positive RF, positive ACPA, high-positive RF, and high-positive ACPA were detectable in 47.2%, 1.1%, 8.9% and 1.1%, respectively. In these patients, fatty liver was an independent factor for high-positive RF. CONCLUSION: In contrast to RF, ACPA is not increased in HCV infection. High-positive RF is not unusually present in nonarthritic patients with chronic HCV infection. ACPA may have improved value for the diagnosis of RA in this patient population. In patients with HCV infection, fatty liver may be a risk factor for high-positive RF.
31888755 OHMI: the ontology of host-microbiome interactions. 2019 Dec 30 BACKGROUND: Host-microbiome interactions (HMIs) are critical for the modulation of biological processes and are associated with several diseases. Extensive HMI studies have generated large amounts of data. We propose that the logical representation of the knowledge derived from these data and the standardized representation of experimental variables and processes can foster integration of data and reproducibility of experiments and thereby further HMI knowledge discovery. METHODS: Through a multi-institutional collaboration, a community-based Ontology of Host-Microbiome Interactions (OHMI) was developed following the Open Biological/Biomedical Ontologies (OBO) Foundry principles. As an OBO library ontology, OHMI leverages established ontologies to create logically structured representations of (1) microbiomes, microbial taxonomy, host species, host anatomical entities, and HMIs under different conditions and (2) associated study protocols and types of data analysis and experimental results. RESULTS: Aligned with the Basic Formal Ontology, OHMI comprises over 1000 terms, including terms imported from more than 10 existing ontologies together with some 500 OHMI-specific terms. A specific OHMI design pattern was generated to represent typical host-microbiome interaction studies. As one major OHMI use case, drawing on data from over 50 peer-reviewed publications, we identified over 100 bacteria and fungi from the gut, oral cavity, skin, and airway that are associated with six rheumatic diseases including rheumatoid arthritis. Our ontological study identified new high-level microbiota taxonomical structures. Two microbiome-related competency questions were also designed and addressed. We were also able to use OHMI to represent statistically significant results identified from a large existing microbiome database data analysis. CONCLUSION: OHMI represents entities and relations in the domain of HMIs. It supports shared knowledge representation, data and metadata standardization and integration, and can be used in formulation of advanced queries for purposes of data analysis.
30747106 Extensive transmission of microbes along the gastrointestinal tract. 2019 Feb 12 The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.
31661133 CP-25 exerts anti-angiogenic effects on a rat model of adjuvant-induced arthritis by promo 2019 Dec Angiogenesis can produce an invasive and destructive front, also named a pannus, comprised of inflammatory vascular tissue that covers and erodes articular cartilage, subchondral bone and peri‑articular soft tissues in rheumatoid arthritis (RA). Paeoniflorin‑6'‑O‑benzene sulfonate (CP‑25) is a novel ester derivative of paeoniflorin. We previously demonstrated that CP‑25 exerts anti‑inflammatory and immunoregulatory effects. CP‑25 also exhibits a marked therapeutic effect on adjuvant‑induced arthritis (AA), and is able to inhibit synovial and immune cell function, according to our previous study. However, the effect of CP‑25 on angiogenesis remains unclear. In the present study, AA was initiated in Sprague‑Dawley rats via intradermal immunization in the right hind metatarsal footpad with heat‑killed Mycobacterium butyricum in liquid paraffin, and rats were divided into four groups: Normal, AA rat model, CP‑25 (50 mg/kg) and methotrexate (0.5 mg/kg) groups (n=10 rats/group). Subsequently, joint synovium in AA rats was pathologically evaluated by hematoxylin and eosin staining, synovial vascular proliferation was evaluated by immunofluorescence, the synovial expression levels of C‑X‑C motif chemokine ligand 12 (CXCL12) were detected by immunohistochemistry and ELISA, and synovial C‑X‑C chemokine receptor type 4 (CXCR4) was detected by western blotting. The results demonstrated that CP‑25 ameliorated clinical signs and pannus formation in the ankle joint in rats with AA. Furthermore, there was a positive correlation between pannus score and CXCL12 and CXCR4 expression. In addition, the effects of CP‑25 on endothelial cell function and CXCL12/CXCR4 signaling were studied in vitro using human umbilical vein endothelial cells (HUVECs). The results demonstrated that CXCL12 significantly promoted HUVEC proliferation, migration and tube formation, and that CP‑25 could reverse these abnormalities by inhibiting plasma membrane localization of G protein‑coupled receptor kinase 2 (GRK2) in HUVECs. These findings suggested that CP‑25 may markedly inhibit pannus formation in AA. This effect may be associated with a reduction in the plasma membrane localization of GRK2 in endothelial cells, an enhancement of the inhibitory effect of GRK2 on ERK1/2 in the cytoplasm, a reduction in the phosphorylation of ERK1/2 and in the function of HUVECs.
31168407 Impact of autoimmune rheumatic diseases on birth outcomes: a population-based study. 2019 OBJECTIVES: Autoimmune rheumatic diseases (ARDs) affect women of childbearing age and have been associated with adverse birth outcomes. The impact of diseases like ankylosing spondylitis and psoriatic arthritis (PsA) on birth outcomes remains less studied to date. Our objective was to evaluate the impact of ARDs on preterm birth (PTB), congenital anomalies, low birth weight (LBW) and small for gestational age (SGA), in a large cohort of women. METHODS: We conducted a propensity score-matched analysis to predict ARD from a retrospective birth cohort of all live, singleton births in California occurring between 2007 and 2012. Data were derived from birth certificate records linked to hospital discharge International Classification of Diseases, ninth revision codes. RESULTS: We matched 10 244 women with a recorded ARD diagnosis (rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome, PsA); ankylosing spondylitis and juvenile idiopathic arthritis (JIA) to those without an ARD diagnosis. The adjusted OR (aOR) of PTB was increased for women with any ARD (aOR 1.93, 95% CI 1.78 to 2.10) and remained significant for those with RA, SLE, PsA and JIA. The odds of LBW and SGA were also significantly increased among women with an ARD diagnosis. ARDs were not associated with increased odds of congenital anomalies. CONCLUSION: Consistent with prior literature, we found that women with ARDs are more likely to have PTB or deliver an SGA infant. Some reassurance is provided that an increase in congenital anomalies was not found even in this large cohort.
31316573 Electroacupuncture on ST36 and GB39 Acupoints Inhibits Synovial Angiogenesis via Downregul 2019 Introduction. The hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) play a key role in synovial angiogenesis in rheumatoid arthritis (RA). Therefore, this study aimed to test the hypothesis that electroacupuncture (EA) may inhibit RA synovial angiogenesis via HIF-1α/VEGF expression. Methods. Sprague-Dawley rats were randomly distributed to 4 groups: control, adjuvant arthritis (AA), AA+electroacupuncture (AA+EA), and AA+sham EA groups. AA model was induced by injection of Freund's complete adjuvant in bilateral hind footpad. 3 days after injection, EA was delivered to the acupoints Zusanli (ST 36) and Xuanzhong (GB 39) once every two days for a total of 8 times in the AA+EA group, while sham EA treatment was applied in the AA+sham EA group. The arthritis score, paw volume, and H&E staining for each animal were measured. CD34 expression in synovial tissue of ankle joint was observed by immunohistochemistry. HIF-1α and VEGF mRNA and protein levels in synovial tissue were determined by real-time quantitative PCR and Western blot, respectively. Results. Compared with rats in AA group, EA stimulation significantly decreased arthritis scores, paw volume, and pathological damage of synovial tissues. Moreover, EA markedly suppressed the synovial angiogenesis of AA rats, as evidenced by reduced CD34 positive expression. Furthermore, EA significantly reduced HIF-1α and VEGF mRNA and protein levels in synovial of AA rats. Finally, the CD34 expression in synovial tissue was positively correlated with HIF-1α and VEGF protein levels. Conclusion. EA on ST36 and GB39 acupoints can effectively inhibit synovial angiogenesis in the AA rat model via downregulating HIF-1α/VEGF expression.
31685753 Reactions of Methotrexate with Hypobromous Acid and Hypochlorous Acid. 2019 Methotrexate is a folate antagonist cytotoxic drug employed in the therapy of cancers and rheumatoid arthritis. Hypobromous acid (HOBr) and hypochlorous acid (HOCl) are generated by eosinophils and neutrophils at inflammation sites. The administered methotrexate may encounter HOBr and HOCl, and react with them to generate products. When methotrexate was incubated with HOBr or HOCl at pH 7.4 and 37°C for 30 min, a single product was generated almost exclusively in each case, identified as 3'-bromomethotrexate for HOBr and 3'-chloromethotrexate for HOCl. When methotrexate was incubated with HOCl in the presence of NaBr, the concentration of 3'-bromomethotrexate increased with decreasing concentration of 3'-chloromethotrexate in a dose-dependent manner with NaBr, probably due to the formation of HOBr. Free amino acids suppressed the reactions of methotrexate with HOBr and HOCl. Taurine suppressed the HOCl reaction but not the HOBr reaction. These results suggest that 3'-bromomethotrexate and 3'-chloromethotrexate may be generated from methotrexate at inflammation sites in humans, although their formation will be suppressed by coexistent amino acids.
31505924 Carpal tunnel syndrome associated with sarcoidosis in identical twin patients. 2019 Sep 10 Sarcoidosis is a multisystemic disease that may lead to neurologic complications in 10% of the patients. Carpal tunnel syndrome is very rare in sarcoidosis. We present two identical twin sarcoidosis patients with carpal tunnel syndrome. A number of factors may cause carpal tunnel syndrome like wrist anatomy, occupation, diabetes, rheumatoid arthritis, pregnancy and renal failure. Although the above factors do not directly cause carpal tunnel syndrome, they may increase your chances of developing or aggravate median nerve damage as it is in sarcoidosis. Sarcoidosis relevant neuropathy and granulomas may be the primary mechanism of sarcoidosis associated carpal tunnel syndrome. Although rare, carpal tunnel syndrome may be a feature of sarcoidosis that may lead to irreversible damage in cases of delayed diagnosis. The presence of this syndrome in identical twin patients may shed light into the pathogenesis and the genetic transmission of sarcoidosis with the associated carpal tunnel syndrome.
31966030 A Case of Salazosulfapyridine-Induced Hypersensitivity Syndrome in a Rheumatoid Arthritis 2019 Sep We experienced a rare case of drug-induced hypersensitivity syndrome (DIHS) in which salazosulfapyridine (SASP) reactivated human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV), which resulted in a relapse of skin symptoms after changing to mizoribine. At the time of recurrence of skin erythema after the initiation of mizoribine, the serum DNA titers of not HHV-6 but CMV were elevated. A drug-induced lymphocyte stimulation test was negative for mizoribine but positive for SASP. In this case, DIHS developed with SASP in association with HHV-6 and CMV reactivation. The immunocompromised state induced by herpes virus reactivation and mizoribine might have caused the relapse of skin erythema.
31396090 Heme Catabolic Pathway in Inflammation and Immune Disorders. 2019 In recent years, the heme catabolic pathway is considered to play an important regulatory role in cell protection, apoptosis, inflammation, and other physiological and pathological processes. An appropriate amount of heme forms the basic elements of various life activities, while when released in large quantities, it can induce toxicity by mediating oxidative stress and inflammation. Heme oxygenase (HO) -1 can catabolize free heme into carbon monoxide (CO), ferrous iron, and biliverdin (BV)/bilirubin (BR). The diverse functions of these metabolites in immune systems are fascinating. Decades work shows that administration of degradation products of heme such as CO and BV/BR exerts protective activities in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS) and other immune disorders. This review elaborates the molecular and biochemical characterization of heme catabolic pathway, discusses the signal transduction and immunomodulatory mechanism in inflammation and summarizes the promising therapeutic strategies based on this pathway in inflammatory and immune disorders.