Myositis-specific autoantibodies are useful biomarkers to make a diagnosis and predict prognosis of idiopathic inflammatory myopathies. Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) is one of the most representative myositis-specific autoantibodies, however, organ involvement in patients positive for anti-ARS is not limited to the muscles but also skin, joints, and lungs, which constructs spectrums of idiopathic inflammatory myopathies called anti-synthetase syndrome. While individual anti-ARS antibodies have been known to form distinct clinical subsets, little is known regarding their chronological clinical presentation patterns and diagnosis during clinical course.
Objectives
To clarify the clinical characteristics of patients positive for anti-ARS and transition in manifestations and diagnosis during their clinical courses.
Methods
We reviewed consecutive patients with anti-ARS who had visited our hospital between 1998 and 2022 retrospectively. Anti-ARS antibodies were detected and categorized with RNA immunoprecipitation assays. We collected patient clinical characteristics and laboratory parameters including transition of diagnosis, manifestations and, organ involvement from their medical records chronologically. All statistical analyses were performed using JMP 15 (SAS Institute Inc., Cary, NC, USA).
Results
We included 97 patients positive for anti-ARS in the analysis. The mean age was 53.2 years old, and 73 (75%) were female. The types of anti-ARS Ab were anti-Jo-1 (37%), anti-EJ (32%), anti-PL-7 (11%), anti-PL-12 (12%), anti-KS (4%), and anti-OJ (3%). Half of the patients had co-existing other autoantibodies such as anti-SS-A/Ro, anti-SS-B/La, anti-dsDNA, anti-RNP, and/or rheumatoid factor, but the combination of antibodies was not different among each anti-ARS. The initial diagnoses of the patients were polymyositis (22%), dermatomyositis (33%), amyopathic dermatomyositis (13%), and interstitial pneumonia with autoimmune features (27%). Raynaud's phenomenon were observed in 25% of the patients; 19% in patients with anti-Jo-1, 36% in anti-EJ, 11% in anti-PL-7, 30% in anti-PL-12, 25% in anti-KS, and 33% in anti-OJ antibodies. Interstitial lung disease was observed in all patients except for three (two with anti-Jo-1 and one with anti-PL-12). Myositis was diagnosed initially in 72% of patients with anti-Jo-1, 50% with anti-EJ, 40% with anti-PL-7, 42% with anti-PL-12, none with anti-KS, and 67% with anti-OJ antibodies, but additional 6%, 4%, 40%, 8%, 0%, and 0% with those individual antibodies, respectively, were diagnosed with myositis during the mean observation period of 9.6 years. Acute or subacute exacerbation of interstitial lung disease requiring immunosuppressive treatment intensification were observed in 28% of patients with anti-Jo-1, 33% with anti-EJ, 40% with anti-PL-7, 8% with anti-PL-12, 33% with anti-KS, and 67% with anti-OJ antibodies.
Conclusion
Almost all patients positive for anti-ARS positive had interstitial lung disease irrelevant of myositis diagnosis. Patients with anti-Jo-1 were suffering from typical myositis complicated with interstitial lung diseases at initial diagnosis, while patients with anti PL-7 tended to have precedent interstitial lung disease followed by development of myositis during clinical courses. The incidence of acute exacerbation of interstitial lung disease was the lowest in patients with anti-PL12.
Abstract Glycosphingolipids (GSLs) are glycoconjugates that function as mediators of cell adhesion and modulators of signal transduction. Some well-defined markers of undifferentiated human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) are glycoconjugates, such as SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. However, Comprehensive GSL profiles of hiPSCs have not yet been elucidated. The global images of GSLs from the parental cells, hiPSCs and differentiated cells revealed that there are parental cell-independent specific glycolipids, including Globo H (fucosyl-Gb5Cer) and H type1 antigen (fucosyl-Lc4Cer) that are novel markers for undifferentiated hiPSCs. Interestingly, undifferentiated hiPSCs expressed H type 1 antigen, specific for blood type O, regardless of the cells’ genotypes. Thus, in this study, we defined the dynamics of GSL remodeling during reprogramming from parental cell sets to iPSC sets and thence to iPSC-neural cells.
n-Octyl beta-D-thioglucopyranoside, a new non-ionic detergent, was synthesized. Properties, and applicability to membrane proteins, of this detergent were investigated. The detergent was easily removed by dialysis. The solubilizing power of this detergent for Escherichia coli membrane proteins was similar to that of n-octyl beta-D-glucopyranoside, which has been widely used in membrane biochemistry. No inactivation of proteins was observed after the solubilization. n-Octyl beta-D-thioglucopyranoside was superior to n-octyl beta-D-glucopyranoside in that it was much more stable and could be synthesized at much lower cost.
Patients with rheumatoid arthritis (RA) have a high prevalence of chronic kidney disease (CKD), which is associated with chronic inflammation, immune-mediated glomerular injury, micro-vasculopathy, and treatment-related nephrotoxicity [1,2]. Elevation of C-reactive protein (CRP) and disease activity are associated with CKD progression in patients treated with biological disease modifying anti-rheumatic drugs (bDMARDs) [3]. Meanwhile, methotrexate (MTX) has mild nephrotoxicity and shows dose-dependent renal impairment [4]. Therefore, in patients treated with MTX, there may be a contradictory relationship between treatment intensity and disease activity.
Objectives:
To identify factors associated with progression of CKD in patients with RA treated MTX.
Methods:
We reviewed consecutive patients with RA who were treated with MTX with stable RA condition for more than five years from 2018 to 2023. Patients who had CKD or started concomitant bDMARDs were excluded. We collected clinical characteristics including CDAI, CRP levels, erythrocyte sedimentation rates, estimated glomerular filtration rate, MTX dose, glucocorticoid use, and concomitant conventional synthetic DMARDs. CKD progression was defined as eGFR level <60 ml/min/1.73m2 at two measurements more than 90 days apart.
Results:
A total of 115 patients were included in the study. The mean age was 62 years, female was 100 (87%), and the mean eGFR at MTX initiation was 84 ml/min/1.73m2. During 5 years of observation, 22 patients (19.1%) progressed to CKD. Patients in the CKD progression group were older, (71 years vs 60 years, p<0.001), used other concomitant csDMARDs more frequently (p=0.020), and showed lower eGFR (73 vs 86 ml/min/1.73m2, p=0.010) at MTX initiation. Moreover, the mean CDAI levels over 5 years in the CKD progression group was significantly higher than the non-CKD progression group (5.8 vs 2.4, p=0.006). Then, we focused on 83 patients who were treated with MTX monotherapy for more than five years. The mean age was 63 years, and 72 (87%) were female. The mean dose of methotrexate was 8.1 mg/week, and the mean CDAI during 5 years was 2.6. During the 5-year observation period, 12 patients (14.6%) progressed to CKD. Patients in the CKD progression group were older (76 years vs 60 years, p<0.010) and were more frequently complicated with hypertension (33% vs 8.4%, p=0.030). Again, the mean CDAI during 5 years in the CKD progression group was significantly high (6.5 vs 1.9, p=0.010). The dose was not different between the two groups (8.5 vs 8.0 mg/week, p=0.700). Multivariable analysis revealed that eGFR at MTX initiation (odds ratio [OR] 0.58, p=0.002) and mean CDAI levels for five years (OR 1.86, p=0.001) are independently associated with CKD progression. A receiver operating characteristic curve identified 3.9 as a cut-off value of CDAI and 75 ml/min/1.73m2 of eGFR at MTX initiation to discriminate patients with CKD progression from those without.
Conclusion:
Mild decrease in eGFR at MTX initiation and strict control of disease activity were crucial to prevent progression to CKD in patients with RA who were treated with MTX, while the MTX dose are not relevant with progression of CKD.
REFERENCES:
[1] Scott DL. Rheumatoid arthritis. Lancet. 2010;376(9746):1094-1108. [2] Sihvonen S. Neohron Clin Pract 2004; 96: c107-c114 [3] Hironari H. Clin Kidney J. 2022 Jan 31;15(7):1373-1378. [4] Hayashi K. Sci Rep. 2020 Oct 30;10(1):18715.
Acknowledgements:
NIL.
Disclosure of Interests:
Inokuchi Hajime: None declared, Hironari Hanaoka: None declared, Kazuoto Hiramoto: None declared, Jun Kikuchi: None declared, Mitsuhiro Akiyama: None declared, Shuntaro Saito: None declared, Yasushi Kondo: None declared, Yuko Kaneko She has received research funding from Pfizer.
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