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Respiratory Research May 2024To investigate the association of serum anti-Jo-1 antibody levels with the disease activity and prognosis in anti-Jo-1-positive patients with antisynthetase syndrome...
OBJECTIVE
To investigate the association of serum anti-Jo-1 antibody levels with the disease activity and prognosis in anti-Jo-1-positive patients with antisynthetase syndrome (ASS).
METHODS
This study included 115 anti-Jo-1-positive patients with ASS who were admitted to China-Japan Friendship Hospital between 2009 and 2019. Anti-Jo-1 antibody serum levels at initial admission and follow-up were determined by enzyme-linked immunosorbent assay (ELISA). Global and organ disease activity was assessed at baseline and follow-up according to the International Myositis Assessment and Clinical Studies guidelines.
RESULTS
Among enrolled patients, 70 (60.9%) patients initially presented with interstitial lung disease (ILD), and 46 (40%) patients presented with with muscle weakness at initial admission. At baseline, patients with ILD had lower levels of anti-Jo-1 antibodies than those without ILD (p = 0.012). Baseline anti-Jo-1 antibody levels were higher in patients with muscle weakness, skin involvement, and arthritis (all p < 0.05) compared to those without these manifestations. Baseline anti-Jo-1 antibody levels were positively correlated with skin visual analogue scale (VAS) scores (r = 0.25, p = 0.006), but not with disease activity in other organs. However, changes in anti-Jo-1 antibody levels were significantly positively correlated with the changes in PGA (β = 0.002, p = 0.001), muscle (β = 0.003, p < 0.0001), and pulmonary (β = 0.002, p = 0.013) VAS scores, but not with skin and joint VAS scores. Older age of onset (hazard ratio [HR] 1.069, 95% confidence interval [CI]:1.010-1.133, p = 0.022) and higher C-reactive protein (CRP) levels (HR 1.333, 95% CI: 1.035-1.717, p = 0.026) were risk factors for death.
CONCLUSION
Anti-Jo-1 titers appear to correlate more with disease activity changes over time rather than with organ involvement at baseline, which provides better clinical guidance for assessing the disease course using anti-Jo-1 levels.
Topics: Humans; Myositis; Male; Female; Middle Aged; Prognosis; Adult; Antibodies, Antinuclear; Follow-Up Studies; Aged; Retrospective Studies; Biomarkers; Lung Diseases, Interstitial
PubMed: 38811943
DOI: 10.1186/s12931-024-02851-w -
Caspian Journal of Internal Medicine 2024Intracranial inflammatory pseudotumours (IPT) are rare entities that frequently lead to misdiagnosis with malignant lesions. The identification of these lesions is...
BACKGROUND
Intracranial inflammatory pseudotumours (IPT) are rare entities that frequently lead to misdiagnosis with malignant lesions. The identification of these lesions is difficult, but important to avoid inadvertent iatrogenicity and to adjust therapeutic protocols.
CASE PRESENTATION
We report the case of a 30-year-old man who presented a single tonic-clonic seizure. Brain imaging showed a right frontal lesion with intra and extra axial components. Facing the radiologic presentation, a brain tumor was suspected, thus the patient underwent surgery. Pathological exam concluded to a plasma cell granuloma. A whole-body CT-scan showed only a thoracic aortitis. Complete blood work studies came back negative. The patient was also tested for an array of antibodies among which antinuclear antibodies were positive (blood level superior to 1/100). CSF evaluation revealed clear fluid with normal glucose concentration, normal protein levels and lymphocytic pleocytosis. Finally, IgG-4 plasma levels were elevated which led to the diagnosis of an IgG4-RD. The patient was put under prednisolone with a favorable outcome.
CONCLUSION
IPT have several etiologies, among which IgG4 related disease may be one of the less known as only 2 cases have previously been reported. Herein, we report a new case of a young man who presented for seizures related to an intracranial lesion of an IgG4 related disease. The challenge is to suspect such conditions to avoid unnecessary surgeries.
PubMed: 38807725
DOI: 10.22088/cjim.15.2.354 -
Lupus Science & Medicine May 2024To investigate the effectiveness of belimumab on active lupus nephritis (LN) and explore the predictors, including serological biomarkers, of renal response to belimumab... (Observational Study)
Observational Study
OBJECTIVES
To investigate the effectiveness of belimumab on active lupus nephritis (LN) and explore the predictors, including serological biomarkers, of renal response to belimumab in a real-world setting.
METHODS
This multicentre, real-world observational study enrolled patients with active LN receiving intravenous belimumab as an add-on therapy with 24-hour urine protein≥1 g and estimated glomerular filtration rate≥30 mL/min/1.73 m at baseline. Complete renal response (CRR), partial renal response (PRR), no renal response (NRR) and primary efficacy renal response (PERR) were evaluated. Multivariable logistic regression was used to identify risk factors for NRR to belimumab at 6 months.
RESULTS
Among the 122 patients enrolled, the proportions of patients achieving CRR, PRR, NRR and PERR were 35.9%, 17.1%, 47.0% and 44.4% at 6 months (n=117) and 55.6%, 19.4%, 26.4% and 58.3% at 12 months (n=72), respectively. Proteinuria, daily prednisone dosage and Systemic Lupus Erythematosus Disease Activity Index 2000 scores significantly decreased at 6 and 12 months (p<0.0001). NRR at 6 months (NRR6) was the strongest negative predictor of CRR at 12 months. Baseline anti-dsDNA positivity inversely predicted NRR6 (OR=0.32,95% CI=0.10 to 0.98, p=0.049), while anti-SSA/Ro60 positively predicted NRR6 (OR=3.16, 95% CI=1.14 to 8.74, p=0.027). The combination of anti-SSA/Ro60 and anti-dsDNA serotype quantitatively predicted belimumab renal response.
CONCLUSION
The effectiveness of belimumab was reproducible in Chinese patients with active LN. The simple yet interesting serotype predictive model needs further validation and its possible underlying mechanistic relevance deserves further exploration.
Topics: Humans; Lupus Nephritis; Female; Male; Antibodies, Monoclonal, Humanized; Adult; Antibodies, Antinuclear; Immunosuppressive Agents; Middle Aged; Glomerular Filtration Rate; Treatment Outcome; Kidney; Biomarkers; Young Adult; Proteinuria; DNA
PubMed: 38806217
DOI: 10.1136/lupus-2024-001156 -
RMD Open May 2024Clinical observation suggests that vascular activation and autoimmunity precede remodelling of the extracellular matrix (ECM) in systemic sclerosis (SSc). We challenge...
OBJECTIVE
Clinical observation suggests that vascular activation and autoimmunity precede remodelling of the extracellular matrix (ECM) in systemic sclerosis (SSc). We challenge this paradigm by hypothesising that ECM biomarkers are already disturbed in patients with very early SSc (veSSc) when fibrosis is not yet clinically detectable.
METHODS
42 patients with veSSc, defined as the presence of Raynaud's phenomenon and at least one of puffy fingers, positive antinuclear antibodies or pathological nailfold capillaroscopy, not meeting the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for SSc, were compared with healthy controls (HCs, n=29). ECM degradation (BGM, C3M, C4M and C6M) and ECM formation biomarkers (PRO-C3, PRO-C4 and PRO-C5) were measured in serum using ELISAs. A cross-sectional analysis at baseline and a longitudinal analysis was performed.
RESULTS
Compared with HC, veSSc patients showed a strongly dysregulated turnover of type III and IV collagens (higher C3M, C4M, both p<0.0001 and PRO-C3, p=0.004, lower turnover ratios PRO-C3/C3M and PRO-C4/C4M, both p<0.0001). The biglycan degradation biomarker BGM was higher in veSSc than in HC (p=0.006), whereas the degradation biomarker for type VI collagen, C6M, was lower (p=0.002). In an ROC analysis, biomarkers of type III and IV collagen excellently distinguished between veSSc and HC: C3M, AUC=0.95, p<0.0001; C4M, AUC=0.97, p<0.0001; turnover ratios PRO-C3/C3M, AUC=0.80, p<0.0001; PRO-C4/C4M, AUC=0.97; p<0.0001.
CONCLUSION
These findings indicate ECM remodelling as a very early phenomenon of SSc occurring in parallel with microvascular and autoimmune changes. Biomarkers of type III and IV collagens distinguished between veSSc patients and HC, indicating them as potential biomarkers for the detection of veSSc.
Topics: Humans; Scleroderma, Systemic; Biomarkers; Female; Male; Middle Aged; Adult; Extracellular Matrix; Collagen; Case-Control Studies; Cross-Sectional Studies; ROC Curve; Aged; Biglycan; Collagen Type III
PubMed: 38806188
DOI: 10.1136/rmdopen-2023-003306 -
Reumatologia 2024The aims were to study the sociodemographic characteristics of patients presenting to the clinic and to study the clinical and serological pattern of systemic lupus...
INTRODUCTION
The aims were to study the sociodemographic characteristics of patients presenting to the clinic and to study the clinical and serological pattern of systemic lupus erythematosus (SLE) in a new rheumatology clinic of a predominantly Yoruba population.
MATERIAL AND METHODS
This was a retrospective, cross-sectional study conducted over 7 years (January 2017 - December 2023). Patients who satisfied the 1997 American College of Rheumatology (ACR) and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria were enrolled using their medical records. Patients with overlap syndromes and other inflammatory or noninflammatory rheumatic diseases were excluded from the study. Their sociodemographic, clinical, laboratory, and treatment data were retrieved from their medical records and analysed using IBM SPSS version 23.0 software.
RESULTS
A total of 65 patients were diagnosed with SLE with a frequency of 15.8%. The mean age ±SD of the patients at presentation was 33.85 years ±11.01 and the female to male ratio was 9.8 : 1. The median (IQR) duration of symptoms at presentation was 7.0 months (3-24). The common clinical presentations included synovitis (86.2%), acute cutaneous rash (53.8%), oral ulcers (52.3%), nonscarring alopecia (50.8%), and serositis (47.7%). Proteinuria was seen in 37.7% of the patients and the predominant renal histopathological feature was Class IV. Antinuclear antibody was 100% positive with 50.94% of the patients having a titre of 1 : 5,120 and above. Anti-double-stranded deoxyribonucleic acid and anti-Smith antibodies each had 50% prevalence. Dyslipidaemia was found in 76.7% of the patients.
CONCLUSIONS
The study's findings are largely consistent with similar studies done in Africa. Further prospective multi-centred studies are needed to further determine the epidemiological characteristics of the disease in Nigeria with a multi-ethnic population.
PubMed: 38799780
DOI: 10.5114/reum/187208 -
Reumatologia 2024The aim was to present effective approaches utilizing novel hematological parameters for early diagnosis of juvenile-onset systemic lupus erythematosus (jSLE).
INTRODUCTION
The aim was to present effective approaches utilizing novel hematological parameters for early diagnosis of juvenile-onset systemic lupus erythematosus (jSLE).
MATERIAL AND METHODS
Our study at Umraniye Training and Research Hospital involved a jSLE patient cohort from 2016 to 2022 and matched healthy controls aligning with sex and age. We use the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) for disease activity. Our approach was to analyze leukocyte, neutrophil, lymphocyte, monocyte, and platelet counts, along with ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and monocyte-to-platelet ratio (MPR). We also explored novel indices: the systemic inflammatory index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) to identify relationships between systemic indices and jSLE activity.
RESULTS
Upon comparative analysis with the healthy control group, systemic lupus erythematosus (SLE) patients exhibited significantly elevated levels of the hematological parameters NLR, SII, and SIRI (-values: 0.010, 0.048, 0.025, respectively). Among SLE patients, neutrophil, lymphocyte, and platelet distribution width (PDW) values were notably higher, while hemoglobin, red blood cell distribution width (RDW), and procalcitonin (PCT) values were significantly lower. In comparison, C-reactive protein (CRP) and sedimentation values were markedly elevated in the SLE group in contrast to the healthy control cohort. Patients with significantly elevated disease activity had notably higher values of NLR ( = 0.010) and SII ( = 0.048). Among patients with positive antinuclear antibodies (ANA), elevated levels of NLR, SII, and SIRI were noted (-values: 0.018, 0.021, 0.035).
CONCLUSIONS
In this study, the novel hematological markers SII, SIRI, and AISI were found to effectively reflect inflammation in SLE patients, exhibit associations with high disease activity, and demonstrate heightened sensitivity in detecting cases with high disease activity.
PubMed: 38799776
DOI: 10.5114/reum/186826 -
Immunity, Inflammation and Disease May 2024The dysregulated immune response is one of the cardinal features of severe coronavirus disease 2019 (COVID-19). This study was conducted to clarify the occurrence of...
OBJECTIVES
The dysregulated immune response is one of the cardinal features of severe coronavirus disease 2019 (COVID-19). This study was conducted to clarify the occurrence of autoantibodies (AABs) associated with systemic autoimmune rheumatic diseases (SARDs) in hospitalized patients with a moderate, severe, and critical form of COVID-19.
METHODS
The serum samples obtained from 176 hospitalized COVID-19 patients were investigated in this study, including patients with moderate (N = 90), severe (N = 50), and critical (N = 36) forms of COVID-19. Also, the serum samples collected from healthy subjects before the COVID-19 pandemic were used as controls (N = 176). The antinuclear antibodies (ANAs), antidouble-stranded DNA (anti-dsDNA), cytoplasmic-anti neutrophil cytoplasmic antibody (c-ANCA), perinuclear ANCA (p-ANCA), antiphospholipid antibodies (aPLs), and anticyclic citrullinated peptide (anti-CCP) occurrence was evaluated using a solid-phase enzyme-linked immunosorbent assay (ELISA).
RESULTS
The results showed that the occurrence of ANAs, anti-dsDNA, anti-CCP, c-ANCA, and p-ANCA was significantly higher in the COVID-19 patients compared to serum obtained from healthy subjects (p < .0001, p < .0001, p < .0001, p < .05, and p < .001, respectively). The positive number of anti-CCP tests increased significantly in severe COVID-19 compared to the moderate group (p < .01).
CONCLUSION
Our study further supports the development of autoantibodies related to systemic autoimmune rheumatologic diseases. To the best of our knowledge, this is the first study with a large sample size that reported the occurrence of anti-CCP in a severe form of COVID-19.
Topics: Humans; COVID-19; Male; Female; Middle Aged; SARS-CoV-2; Adult; Aged; Anti-Citrullinated Protein Antibodies; Autoantibodies; Severity of Illness Index; Antibodies, Antinuclear; Rheumatic Diseases; Autoimmune Diseases
PubMed: 38780036
DOI: 10.1002/iid3.1276 -
Archives of Rheumatology Mar 2024
PubMed: 38774693
DOI: 10.46497/ArchRheumatol.2024.9942 -
Heliyon May 2024Schizophrenia is a syndrome with multiple etiologies, one of which is the potential for an autoimmune disease of the brain such as N-methyl-d-aspartate receptor (NMDAR)...
Schizophrenia is a syndrome with multiple etiologies, one of which is the potential for an autoimmune disease of the brain such as N-methyl-d-aspartate receptor (NMDAR) encephalitis, which can induce psychosis resembling schizophrenia. Here, we examined anti-neuronal autoantibodies related to psychosis using both cell- (CBA) and tissue-based assays (TBA) in the cerebrospinal fluid (CSF) of patients with chronic schizophrenia and control participants. First, we screened for the antibodies against leucine-rich glioma-inactivated 1 (LGI1), γ-aminobutyric acid B receptor (GABABR), dipeptidyl aminopeptidase-like protein 6 (DPPX), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR1/R2), and contactin-associated protein-like 2 (CASPR2) in 148 patients with schizophrenia. No antibodies were detected. Next, we performed CBA for NMDAR antibodies in 148 patients with schizophrenia and 151 age- and sex-matched controls. Although we detected relatively weak immunoreactivity for NMDAR in the CSFs of two patients with schizophrenia and three controls, no samples were positive when strict criteria were applied. For TBA in the rat hippocampus and cerebellum, we detected positive signals in the CSFs of 13 patients with schizophrenia and eight controls. Positive samples were analyzed for paraneoplastic syndrome and antinuclear antibodies using immunoblotting. The CSFs of nine patients and six controls were positive for dense fine speckle 70 (DFS70) antibodies. Additionally, antibodies against centromere protein (CENP)-A and CENP-B were detected in patients with schizophrenia. Our results suggest that autoantibodies against NMDAR, LG1, GABABR, DPPX, AMPAR1/R2, and CASPR2 are not associated with the pathogenesis of chronic schizophrenia. Moreover, we emphasize the importance of considering the effect of anti-DFS70 antibodies when analyzing autoantibodies in CSF samples. Conclusively, we obtained no evidence suggesting that the most frequent neuronal autoantibodies in the CSF play a role in the pathogenesis of schizophrenia, even in our sample.
PubMed: 38770306
DOI: 10.1016/j.heliyon.2024.e30695 -
Canadian Liver Journal May 2024Metabolic dysfunction associated steatotic liver disease (MASLD) and metabolic dysfunction associated steatohepatitis (MASH) are rapidly growing public health concerns....
BACKGROUND
Metabolic dysfunction associated steatotic liver disease (MASLD) and metabolic dysfunction associated steatohepatitis (MASH) are rapidly growing public health concerns. Identifying predictive markers for advanced liver disease in MASLD patients is crucial for early intervention. This study investigates the association between autoantibody positivity and risk for severe fibrosis or cirrhosis across various subgroups.
METHODS
We conducted a retrospective study of adult patients diagnosed with MASLD between 1994 and 2019. Autoantibody status (anti-nuclear and anti-smooth muscle antibodies) was assessed using laboratory studies. Hepatic fibrosis or cirrhosis was determined histologically or through accepted non-invasive measures. Logistic regression analyses were employed to evaluate the association between autoantibody positivity and severe fibrosis or cirrhosis. Patients with comorbid viral and alcohol liver disease were assessed separately.
RESULTS
Among 2,749 MASLD patients, 1,425 (51.8%) were male and 1,324 (48.2%) were female, with a mean age of 58.7 years. A total of 541 (19.7%) patients tested positive for autoantibodies. Autoantibody positivity was associated with a higher risk of severe fibrosis or cirrhosis in MASLD patients (odds ratio 1.28, 95% CI [1.0-1.6]). This association persisted across various subgroups, including those with concurrent hepatitis B and C virus infections. In contrast, in alcohol liver disease, autoantibody-positive patients exhibited a lower risk.
CONCLUSION
Autoantibody positivity emerges as a potential predictive marker for advanced liver disease in MASLD patients, facilitating risk stratification and tailored interventions. This study highlights the clinical relevance of autoantibodies in MASLD and underscores the need for prospective validation and mechanistic investigations to refine risk assessment and management strategies.
PubMed: 38746864
DOI: 10.3138/canlivj-2023-0026