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Purpose: Inflammation triggers a metabolic shift in macrophages from oxidative phosphorylation to glycolysis, a phenomenon known as the Warburg effect. This metabolic reprogramming worsens inflammation and cascades into organ damage. Angiotensin-(1-7) [Ang-(1-7)], a small molecule, has demonstrated anti-inflammatory properties. This study investigates whether Ang-(1-7) mitigates inflammation in LPS-induced macrophages and septic mice by regulating the Warburg effect in immune metabolism. Methods: The study induced macrophages with LPS in vitro and measured inflammatory factors using ELISA and Western blot. Key enzymes in glycolysis, mitochondrial respiratory complexes, and citrate pathway key molecules were assessed using Western blot and qRT-PCR. Mitochondrial membrane potential (MMP), lactate, and ATP were measured using assay kits. In vivo, a mouse model of sepsis induced by LPS was used. Kidney tissues were examined for pathological and mitochondrial ultrastructural alterations. The levels of inflammatory factors in mouse serum, glycolysis and citrate pathway-related molecules in the kidney were assessed using qRT-PCR, Western blot, and immunofluorescence techniques. Additionally, MMP, lactate, and ATP in the kidney were measured using assay kits. Results: In vitro experiments demonstrated that Ang-(1-7) inhibited the levels of inflammatory factors in LPS-treated RAW264.7 cells. It also reduced the expression of key glycolytic enzymes HK2, PFKFB3, and PKM2, as well as lactate levels. Additionally, it decreased intracellular citrate accumulation, enhanced mitochondrial respiratory complexes I and III, and ATP levels. Ang-(1-7) alleviated MMP damage, modulated citrate pathway-related molecules, including SLC25A1, ACLY, and HIF-1α. In vivo experiments showed that Ang-(1-7) lowered glycolysis levels in septic mice, improved mitochondrial ultrastructure and function, mitigated inflammation and renal tissues damage in septic mice, and suppressed the expression of key molecules in the citrate pathway. Conclusion: In conclusion, Ang-(1-7) can regulate the Warburg effect through the citrate pathway, thereby alleviating inflammation in LPS-induced macrophages and septic mice.
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Pulmonary fibrosis (PF) is a chronic, progressive interstitial lung disease characterized by diffuse alveolar inflammation, fibroblast differentiation, and the excessive deposition of extracellular matrix. During the progression of PF, redox imbalance caused by excessive reactive oxygen species (ROS) production can result in further destruction of lung tissue. At present, data on the role of NADPH oxidase-4 (Nox4)-nuclear factor erythroid 2-related factor 2 (Nrf2) redox imbalance in PF are limited. The angiotensin (1-7) [Ang-(1-7)]/Mas axis is a protective axis in the renin-angiotensin system (RAS) that exerts antifibrotic effects. Therefore, this study aimed to investigate the role of the Ang-(1-7)/Mas axis in PF and to explore its mechanism in depth. The results revealed that the Ang-(1-7)/Mas axis inhibited TGF-ß1-induced lung fibroblast differentiation, inflammation and fibrosis in bleomycin (BLM)-treated lung tissue. A mechanistic study suggested that the Ang-(1-7)/Mas axis may restore Nox4-Nrf2 redox homeostasis by upregulating the level of p62, reducing oxidative stress and the inflammatory response and thus delaying the progression of lung fibrosis. This study provides a theoretical basis for exploring the mechanisms of PF and therapeutic targets for PF.
Subject(s)
Pulmonary Fibrosis , Mice , Animals , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , NF-E2-Related Factor 2/metabolism , Bleomycin/adverse effects , Peptidyl-Dipeptidase A/metabolism , Lung , Inflammation , Oxidation-Reduction , Homeostasis , NADPH Oxidase 4ABSTRACT
OBJECTIVES: To investigate the clinical characteristics of subcutaneous emphysema (SE) and mediastinal emphysema (ME) occurring in patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis associated with interstitial lung disease (anti-MDA5-positive DM-ILD). METHODS: In this retrospective study, a total of 117 anti-MDA5-positive DM-ILD patients were admitted to our hospital. All patients underwent an assessment of autoantibodies, serum ferritin levels, and lung high-resolution CT scans. RESULTS: In patients with anti-MDA5-positive DM-ILD, the incidence of SE/ME was found to be 11.1%, which was significantly higher compared to patients with anti-synthetase syndrome (p<0.01). The mortality rate among anti-MDA5-positive DM-ILD patients with SE/ME was significantly higher than those without SE/ME (p=0.0022). There was no statistically significant difference in the occurrence of SE/ME between patients with positive anti-Ro-52 antibodies and those with negative anti-Ro-52 antibodies (p=0.18). Patients with higher serum ferritin levels (1000 ng/ml ≤serum ferritin ≤1500 ng/ml) had a higher likelihood of developing SE/ME compared to patients with lower serum ferritin levels (serum ferritin <500 ng/ml) (p<0.01). Among 13 anti-MDA5-positive DM-ILD patients with SE/ME, six (46.2%) developed SE/ME within 1 month of being diagnosed and 53.8% of patients underwent positive pressure ventilation prior to the onset of SE/ME. CONCLUSIONS: We found that SE/ME is not uncommon in anti-MDA5-positive DM-ILD and is an important factor associated with poor patient prognosis. The occurrence of SE/ME is correlated with high levels of serum ferritin and is not related to anti-Ro-52 antibodies. Rheumatologists should pay close attention to SE/ME caused by positive pressure ventilation in anti-MDA5-positive DM-ILD patients.
Subject(s)
Dermatomyositis , Lung Diseases, Interstitial , Mediastinal Emphysema , Humans , Prognosis , Retrospective Studies , Mediastinal Emphysema/complications , Interferon-Induced Helicase, IFIH1 , Lung Diseases, Interstitial/diagnosis , Autoantibodies , FerritinsABSTRACT
OBJECTIVE: We sought to investigate the reasons why spondyloarthritis (SpA) patients failed to respond to non-steroidal anti-inflammatory drugs (NSAIDs) and conventional synthetic disease-modifying antirheumatic drugs (cDMARDs) and the influences of different initial cDMARDs on the likelihood of a switch to biologics. METHODS: SpA patients were divided into a conventional drug maintenance group and a biologics conversion group to determine the causes of conversion to biologics. Then, we divided all patients into three groups according to different initial cDMARDs, NSAID monotherapy, NSAID + (sulfasalazine or thalidomide) double combination, and NSAID + sulfasalazine + thalidomide triple combination therapy groups, to clarify the influence of initial treatment on later conversion to biologics. RESULTS: This study includes 202 patients, including 97 patients in the conventional drug maintenance group and 105 patients in the biologics conversion group. The mean age of the conventional drug maintenance group was higher than that of the biologics conversion group (40.8 ± 14.3 vs. 33.8 ± 12.3 years, P < 0.05). Uveitis (OR 5.356, P < 0.05) is positively correlated with conversion to biological therapy, while age (OR 0.940, P < 0.05) is negatively correlated. The proportion of NSAID monotherapy, double combination, and triple combination groups converted to biological agents was 80%, 51.1%, and 23.2%, respectively (P < 0.05). CONCLUSION: Age and uveitis are related to conversion to biologics therapy. The early combination of sulfasalazine and thalidomide with NSAIDs may lower the probability of conversion to biologics therapy in the later stage and offer a new option for patients with limited use of biologics in SpA patients. Key Points ⢠Patients' move to biologics may be caused mostly by inadequate disease control by conventional oral medications. ⢠Regardless of axial vs. peripheral joint involvement, combination drug therapy was superior to single drug therapy in controlling SpA and decreasing the probability of conversion to a biological agent. ⢠For SpA patients who are not candidates for biologics due to contraindications or other reasons, early combination application of NSAIDs, sulfasalazine, and thalidomide may be a new choice.
Subject(s)
Antirheumatic Agents , Biological Products , Spondylarthritis , Uveitis , Humans , Biological Products/therapeutic use , Sulfasalazine/therapeutic use , Thalidomide/therapeutic use , Spondylarthritis/drug therapy , Antirheumatic Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Biological Factors/therapeutic use , Analgesics/therapeutic use , Uveitis/drug therapyABSTRACT
OBJECTIVE: To investigate the clinical usefulness of serum superoxide dismutase (SOD) measurement in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: In this single-center retrospective study, demographic data, serum SOD levels, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), the Birmingham Vasculitis Activity Score (BVAS), ANCA, organ involvement, and outcomes were analyzed for 152 AAV patients hospitalized in the Second Affiliated Hospital of Chongqing Medical University. Meanwhile, the serum SOD levels of 150 healthy people were collected as the control group. RESULTS: Compared to the healthy control group, serum SOD levels of the AAV group were significantly lower (P < 0.001). SOD levels of AAV patients were negatively correlated to ESR, CRP, and BVAS (ESR rho = - 0.367, P < 0.001; CRP rho = - 0.590, P < 0.001; BVAS rho = - 0.488, P < 0.001). SOD levels for the MPO-ANCA group were significantly lower than the PR3-ANCA group (P = 0.045). SOD levels for the pulmonary involvement group and the renal involvement group were significantly lower than those for the non-pulmonary involvement group and the non-renal involvement group (P = 0.006; P < 0.001, respectively). SOD levels in the death group were significantly lower than the survival group (P = 0.001). CONCLUSIONS: In AAV patients, low SOD levels might indicate disease associated oxidative stress. SOD levels in AAV patients were decreased with inflammation, suggesting that SOD levels could potentially be a surrogate marker for disease activity. SOD levels in AAV patients were closely related to ANCA serology, pulmonary involvement, and renal involvement, with low SOD levels an important indicator of a poor prognosis for AAV patients.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Antibodies, Antineutrophil Cytoplasmic , Humans , Retrospective Studies , Inflammation , C-Reactive Protein , Superoxide DismutaseABSTRACT
OBJECTIVE: This study aimed to investigate the relationship between serum superoxide dismutase (SOD) and interstitial lung disease (ILD) among patients with anti-melanoma differentiation-associated gene 5 antibody (MDA5)-positive DM. METHOD: In this retrospective study, serum SOD of 90 health check-ups were tested in our hospital. A total of 94 hospitalized patients with anti-MDA5-positive DM had ILD. Their serum SOD, serum ferritin and autoantibody levels were determined and lung high-resolution CT was performed. RESULTS: The serum SOD level was significantly lower in the anti-MDA5-positive DM group compared with the control group. The SOD level was significantly lower in patients positive for both anti-MDA5 antibodies and anti-Ro-52 antibodies than in those positive for only anti-MDA5 antibodies before treatment. The SOD level was significantly lower in the higher serum ferritin group compared with the lower serum ferritin group before treatment. After treatment, the serum SOD level decreased in patients with exacerbation of ILD, while it increased in those with alleviated ILD. The SOD level was significantly lower in the death group than in the survival group before treatment. CONCLUSIONS: In patients with anti-MDA5-positive DM, the low SOD level before treatment indicated the presence of oxidative stress in the disease; the serum SOD level was affected by anti-Ro-52 antibodies and ferritin; there is a close relationship between serum SOD level and ILD among patients with anti-MDA5-positive DM, suggesting that SOD might serve as an effective indicator to evaluate the changes in ILD in these patients; and the low SOD level is an important indicator of poor prognosis in these patients, which deserves attention from rheumatologists.
Subject(s)
Dermatomyositis , Lung Diseases, Interstitial , Humans , Prognosis , Retrospective Studies , Disease Progression , Interferon-Induced Helicase, IFIH1 , Autoantibodies , FerritinsABSTRACT
Abstract Objective To investigate the clinical usefulness of serum superoxide dismutase (SOD) measurement in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods In this single-center retrospective study, demographic data, serum SOD levels, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), the Birmingham Vasculitis Activity Score (BVAS), ANCA, organ involvement, and outcomes were analyzed for 152 AAV patients hospitalized in the Second Affiliated Hospital of Chongqing Medical University. Meanwhile, the serum SOD levels of 150 healthy people were collected as the control group. Results Compared to the healthy control group, serum SOD levels of the AAV group were significantly lower (P < 0.001). SOD levels of AAV patients were negatively correlated to ESR, CRP, and BVAS (ESR rho = − 0.367, P < 0.001; CRP rho = − 0.590, P < 0.001; BVAS rho = − 0.488, P < 0.001). SOD levels for the MPO-ANCA group were significantly lower than the PR3-ANCA group (P = 0.045). SOD levels for the pulmonary involvement group and the renal involvement group were significantly lower than those for the non-pulmonary involvement group and the non-renal involvement group (P = 0.006; P < 0.001, respectively). SOD levels in the death group were significantly lower than the survival group (P = 0.001). Conclusions In AAV patients, low SOD levels might indicate disease associated oxidative stress. SOD levels in AAV patients were decreased with inflammation, suggesting that SOD levels could potentially be a surrogate marker for disease activity. SOD levels in AAV patients were closely related to ANCA serology, pulmonary involvement, and renal involvement, with low SOD levels an important indicator of a poor prognosis for AAV patients.
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Purpose: To explore the risk factors for thrombi occurring in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and establish a risk prediction model to better predict the risk of thrombosis in patients with AAV. Patients and Methods: We retrospectively analyzed 117 AAV patients who had been hospitalized in The Second Affiliated Hospital of Chongqing Medical University between October 2010 and December 2021. For all patients, we recorded demographic characteristics and clinical data, analyzed the risk factors for thrombosis in AAV patients and then developed a risk prediction model. Results: Stepwise logistic regression analysis indicated that a high complement C3 level, a high BVAS score and a high Padua score were independent risk factors for thrombosis in AAV patients. According to multivariate analysis, a predictive model for thrombus risk was successfully established; the area under the ROC curve(AUC) was 0.803 (95% CI: 0.716-0.890) and the maximum Youden index, sensitivity and specificity were 0.487, 59.0% and 89.7%, respectively. Conclusion: A high complement C3 level, high BVAS score, and a high Padua score were shown to be independent risk factors for thrombosis in AAV patients. We developed a risk prediction model based on these three risk factors that could predict the risk of thrombosis in AAV patients to some extent.
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OBJECTIVE: The aim of our study was to elucidate the potential prognostic factors in anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive patients. METHODS: We divided anti-MDA5-positive patients into death and survival groups. The differences in clinical characteristics were analyzed. RESULTS: A total of 56 cases were included. The death group comprised 10 (17.9%) cases, and the survival group comprised 46 (82.1%) cases. Median age of the death group was greater than the survival group, 59.50 years vs 39.25 years, p<0.05. The death group had lower lymphocyte count and albumin and higher erythrocyte sedimentation rate, ferritin and lactate dehydrogenase initially (p<0.05, respectively). Ground-glass opacity on chest computed tomography was found more often in the death group (p<0.05), in which there was an absence of honey-combed shadow initially. The diagnosis of interstitial pneumonia with autoimmune features was higher in the death group than the survival group (70% vs 13%, p<0.05). The median dose of maximum daily methylprednisolone in the death group (160 mg/d) was higher than that in the survival group (48 mg/d) (p<0.05). CONCLUSION: Advanced age, low lymphocyte count and albumin, and increased levels of inflammatory markers may portend poor prognosis in anti-MDA5-positive patients. Extra-large doses of glucocorticoid may have no additional benefit in these patients.
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OBJECTIVE: Clinical characterization of lipid metabolism in untreated patients with anti-melanoma differentiation-associated gene 5 antibodies-positive (anti-MDA5+). METHODS: Body-mass index (BMI), autoantibodies, lipid levels, and serum ferritin levels in 57 anti-MDA5+ patients were determined in the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University. RESULTS: Plasma high-density lipoprotein (HDL) and apolipoprotein A1 (ApoA1) levels were significantly lower in deceased group than in the survival group (P < 0.05). Plasma levels of HDL and ApoA1 were significantly lower in patients who were simultaneously anti-MDA5+ and anti-Ro-52+ than in patients who were anti-MDA5+ alone (P < 0.05). Plasma levels of total cholesterol, low-density lipoprotein, HDL, and ApoA1 were significantly decreased in patients with high levels of serum ferritin compared with patients with low levels (P < 0.05). There were no significant differences in blood lipid levels between patients grouped according to BMI. CONCLUSION: 1) HDL and ApoA1 levels are important indicators of poor prognosis in anti-MDA5+ patients; 2) Dysregulated lipid metabolism in anti-MDA5+ patients is closely associated with anti-Ro-52 antibody and ferritin levels but independent of BMI; 3) HDL involvement in inflammation and immune regulation merits close attention by rheumatologists.
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Objectives: Rheumatoid arthritis (RA) is a disabling disease with a high incidence that is regularly accompanied by cardiovascular complications. Several studies have suggested that renin-angiotensin-aldosterone system (RAAS) is closely associated with RA. The aim of this study was to investigate the mechanisms underlying Angiotensin-(1-7) [Ang-(1-7)] and its Mas receptor agonist (AVE0991) on joint inflammation and cardiac complications in a collagen-induced arthritis (CIA) model. Methods: Collagen type II was injected into DBA/1 mice to construct an arthritis model. CIA mice were treated with Ang-(1-7) (2.0 mg/kg intraperitoneally) and AVE0991 (3.0 mg/kg intraperitoneally). The serum levels of inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 ß, IL-6, and C-reactive protein (CRP)] were determined by ELISA. The mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) signaling pathways in joint tissues and the transforming growth factor (TGF)-ß/Smad pathway and levels of α-Smooth muscle action (SMA) and ß-myosin heavy chain (MHC) protein expression in cardiac tissues were assessed by western blots. The levels of TGF-ß/Smad pathway, α-SMA, and ß-MHC RNA in cardiac tissues were analyzed by real time-PCR. The levels of receptor activator of nuclear factor kappa ligand (RANKL) and promoting matrix metalloproteinase (MMP)-3 expression in the ankle joints were detected by immunohistochemistry and real time-PCR. Results: Ang-(1-7) and AVE0991 reduced the levels of inflammatory cytokines and inhibited the MAPKs and NF-κB signaling pathways in ankle joint tissues, reduced RANKL and MMP3 expression, and ameliorated local joint inflammation and bone destruction compared with the control group. In addition, Ang-(1-7) and AVE0991 attenuated the TGF-ß/Smad signaling pathway, reduced the levels of α-SMA and ß-MHC expression, and diminished inflammatory cell infiltration into the myocardial interstitium and myocardial interstitial fibrosis in the hearts of CIA mice. Conclusions: Ang-(1-7) alleviated joint damage caused by inflammation likely through the attenuation of NF-κB and MAPK pathways and ameliorated inflammation-induced cardiac fibrosis and activation of the TGF-ß/Smad pathway. Moreover, Ang-(1-7) was likely mediated through the Mas receptor. This study provides theoretical evidence for exploring novel clinical therapeutic approaches for RA and its cardiac complications.
Subject(s)
Angiotensin I/adverse effects , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/etiology , Peptide Fragments/adverse effects , Rheumatic Heart Disease/etiology , Animals , Arthritis, Experimental , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , Biomarkers , Biopsy , Cytokines/blood , Cytokines/metabolism , Disease Models, Animal , Disease Susceptibility , Fibrosis , Immunohistochemistry , Male , Mice , Rheumatic Heart Disease/diagnosis , Signal Transduction , Symptom AssessmentABSTRACT
PURPOSE: Angiotensin 1-7 [Ang-(1-7)] has been identified as an important anti-inflammatory and anti-fibrotic factor. This study determined how the ACE2-Ang-(1-7)-Mas axis affected M1/M2 macrophage polarization and thus contributed to anti-inflammatory processes in the cecal ligation and puncture (CLP)-induced inflammation model. MATERIALS AND METHODS: ELISA, western blotting, and qRT-PCR were used to verify that Ang-(1-7) decreased the expression of pro-inflammatory cytokines and increased anti-inflammatory cytokines. The differentiation of M1/M2 macrophages was assessed by flow cytometry for assessing the cell-surface markers, CD86 and CD206. The related key receptors and pathways were analyzed by Western blotting, qRT-PCR, and immunofluorescence. CLP-induced inflammatory mice models were used for in vivo studies. Hematoxylin and eosin and immunohistochemical and immunofluorescence staining protocols were used to analyze histological changes in the spleen, and the related key pathway proteins were analyzed by western blotting. RESULTS: Ang-(1-7) decreased the expressions of the TNF-α and IL-6 pro-inflammatory cytokines and increased the expressions of the IL-4 and IL-10 anti-inflammatory cytokines. INOS and TNF-α, which represented M1 macrophage polarization, were decreased by Ang-(1-7). ARG1 and CD163, which represented M2 macrophage polarization, were increased by Ang-(1-7). Both Mas receptor and ACE2 are expressed on macrophages. Furthermore, the ACE2-Ang-(1-7)-MAS axis modulated macrophage polarization by ameliorating TLR4 expression and regulating the NF-кB and MAPK pathways. In addition, splenomegaly and macrophage infiltration were observed in the spleen of the CLP-induced mouse models and macrophages in the spleen suspension of CLP models were shifted to M1 phenotype and were effectively inhibited by Ang-(1-7) via the TLR4-mediated NF-кB and MAPK pathways, which could be partially rescued by A-779. CONCLUSION: Ang-(1-7) inhibited inflammatory responses in vivo and in vitro, and repressed macrophage polarization toward the M1 phenotype and promoted it toward the M2 phenotype, which provided new evidence for the anti-inflammation activity of the ACE2-Ang-(1-7)-MAS axis.
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OBJECTIVE: The aim was to investigate the characteristics of blood lymphocytes in patients positive for anti-melanoma differentiation-associated gene 5 antibodies (anti-MDA5+) in interstitial lung disease. METHODS: Thirty-eight anti-MDA5+ patients with interstitial lung disease were admitted to our hospital, and the lymphocyte count, lymphocyte subtypes and lung high-resolution CT were recorded. Some of the cases were examined by bone marrow aspiration. RESULTS: Compared with the control group, the blood lymphocyte counts of anti-MDA5+ patients before treatment were significantly lower (P < 0.05). After treatment, lung interstitial lesions in some cases were reduced and the lymphocyte counts increased, whereas their CD4:CD8 ratio decreased (P < 0.05). In contrast, lung interstitial lesions of other cases were exacerbated after treatment and the lymphocyte counts decreased, whereas the CD4:CD8 ratio increased (P < 0.05). In cases with exacerbated lung interstitial lesions after treatment, there were fewer CD4 and CD8 T cells than before treatment, and the change in CD8 T cells was significant (P < 0.05). Bone marrow aspiration biopsy indicated that there was no abnormality in the distribution of bone marrow lymphocytes. CONCLUSION: Anti-MDA5+ patients showed a decrease in blood lymphocyte counts. The presence of anti-MDA5+ in patients with pulmonary interstitial lesions was positively correlated with blood lymphocyte counts but negatively correlated with the CD4:CD8 ratio. The CD8 T cells decreased more significantly than CD4 T cells in patients with aggravation of interstitial lung disease. The change in blood lymphocytes in anti-MDA5+ patients might be attributable to transfer of lymphocytes to the lungs to participate in the local immune response.
Subject(s)
Autoantibodies/immunology , Interferon-Induced Helicase, IFIH1/immunology , Lung Diseases, Interstitial/immunology , Lymphocytes/immunology , Aged , Aged, 80 and over , CD4-CD8 Ratio , Female , Humans , Lymphocyte Count , Male , Middle AgedABSTRACT
OBJECTIVE: This retrospective clinical study aimed to examine the similarities and differences between connective tissue disease-associated interstitial lung disease (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF) and to identify the influencing factors of CTD-ILD, with a goal of early detection and active treatment of the disease. METHODS: We conducted a retrospective study of 480 patients: 412 with CTD-ILD and 68 with IPAF. Demographic features, clinical characteristics, laboratory indicators, and chest high-resolution computed tomography (HRCT) imaging data were analyzed. RESULTS: Compared with the IPAF group, the CTD-ILD group contained more women, and the incidences of joint pain, dry mouth/dry eyes, and Raynaud's phenomenon were higher; erythrocyte sedimentation rate (ESR) and D-dimer levels were higher; red blood cell (RBC) and hemoglobin (Hb) levels were lower; a high rheumatoid factor (RF) titer (> 2 times the normal upper limit) was observed, and anti-cyclic citrullinated peptide antibody (anti-CCP), anti-keratin antibody (AKA), antinuclear antibody (ANA), and anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5) levels were higher. Compared with CTD-ILD patients, IPAF patients were more likely to present initially with respiratory symptoms, with higher rates of fever, cough and expectoration, dyspnea, and Velcro crackles; anti-Ro52 titers were higher; incidences of honeycombing opacity, reticulate opacity, patchy opacity, and pleural thickening were greater. Female sex, a high RF titer (> 2 times the normal upper limit), anti-CCP positivity, ANA positivity, and anti-MDA5 positivity were risk factors for CTD-ILD when the odds ratios were adjusted. CONCLUSION: CTD-ILD and IPAF patients differed in demographic features, clinical characteristics, laboratory indicators, and chest HRCT imaging data. Female sex, a high RF titer (> 2 times the normal upper limit), anti-CCP positivity, ANA positivity, and anti-MDA5 positivity were risk factors for CTD-ILD.Key Points⢠This retrospective clinical study comprehensively compared the demographic features, clinical characteristics, laboratory indicators, and chest HRCT imaging data of CTD-ILD and IPAF patients.⢠The evidence suggested that female sex, a high RF titer, anti-CCP positivity, ANA positivity, and anti-MDA5 positivity were risk factors for CTD-ILD.
Subject(s)
Connective Tissue Diseases/complications , Diabetes Mellitus, Type 1/complications , Lung Diseases, Interstitial/etiology , Aged , Autoantibodies/blood , Connective Tissue Diseases/blood , Connective Tissue Diseases/diagnostic imaging , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/diagnostic imaging , Diagnosis, Differential , Female , Humans , Lung Diseases, Interstitial/blood , Lung Diseases, Interstitial/diagnostic imaging , Male , Middle Aged , Radiography, Thoracic , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
OBJECTIVES: To investigate the clinical characteristics of patients positive for anti-melanoma differentiation-associated gene 5 (MDA5) antibodies, and to analyse the potential pathogenesis of anti-MDA5 antibodies. METHODS: The clinical manifestations, serological tests, imaging features, treatments, and prognoses of 32 anti-MDA5 antibody-positive patients diagnosed in the Rheumatology and Immunology Department of the Second Affiliated Hospital of Chongqing Medical University from September 2015 to August 2018 were analysed. RESULTS: Of the 32 anti-MDA5 antibody-positive patients, eleven patients were clinically diagnosed with interstitial pneumonia with autoimmune features (IPAF), ten patients were diagnosed with clinically amyopathic dermatomyositis (CADM), six patients were diagnosed with dermatomyositis (DM) and five patients were diagnosed with anti-synthetase syndrome (ASS). Thirty patients had various degrees of pulmonary interstitial changes. The incidence of mortality, subcutaneous emphysema, hoarseness and dysphagia in patients who were positive for both anti-MDA5 and anti-Ro52 antibodies was significantly higher than in patients positive for only anti-MDA5 antibodies. The anti-MDA5 antibody-positive IPAF patients had a very poor prognosis, and mortality in these patients was as high as 54.55%. CONCLUSIONS: Anti-MDA5 antibodies are closely related to interstitial lung disease (ILD). The presence of both anti-MDA5 and anti-Ro52 antibodies indicates poor prognosis.