Systemic lupus erytematosus (SLE) is a multi-organ autoimmune disease that affects women of childbearing age. SLE and lupus nephritis have more maternal and fetal complications than the general population. However, the impact of pregnancy on SLE activity is controversial in the literature, some studies reporting increased risk of lupus flare, while others indicate no increased risk.
Objectives
The aims of this study were to investigate the effect of the pregnancy on disease status, both during the pregnancy and puerparium and the predictors for lupus flare. In addition, we examine lupus activity and pregnancy outcomes in lupus pregnancies continued, discontinued or not treated with Hydroxychloroquine (HCQ) during pregnancy.
Methods
We performed a retrospective analysis of 183 pregnancies in 132 SLE patients managed in Catholic University Medical Center, Korea, between 1998 and 2012. Clinical profiles and maternal and fetal outcomes were assessed for this study population. Lupus flare was assessed with SLEDAI score. Discontinued HCQ group was defined as cessation of HCQ treatment within the 3 months prior to pregnancy. Not treated with HCQ from pre-pregnancy was defined cessation of HCQ treatment beyond 3 months prior to pregnancy.
Results
The pregnancies were divided into 2 groups: experienced lupus flare (84 pregnancies) and not experienced lupus flare (99 pregnancies). 87.4% of pregnancies had successful delivery. There were significantly more preeclampsias (27.4% vs. 7.1%, with and without lupus flare, respectively, P <0.001), preterm births (44% vs. 16.7%, P=0.01), low birth weight (2.42±0.60 kg vs. 2.85±0.54 kg, P<0.001), intrauterine growth retardation (38.6% vs. 18.9%, P=0.006) and low 1 minute Apgar score (25.7% vs. 8.9%, P=0.004) in pregnancies with lupus flare. Lupus flares were predicted by discontinuation of HCQ (OR=4.968, 95% CI, 1.114-22.145; p=0.036), history of lupus nephritis (OR, 4.417; 95% CI 1.253-15.575, p=0.021), active disease status at conception (OR, 4.526; 95% CI, 1.276-16.049; p=0.019), high serum uric acid level (OR, 2.624; 95% CI, 1.414-4.868; p=0.002) and C4 level at pre-pregnancy (OR 0.858, 95% CI 0.762-0.966; p=0.011).
Conclusions
Our study indicates that achieving remission before pregnancy and continuing HCQ treatment during pregnancy are important to prevent lupus flare during pregnancy.
References
Stojan G and Baer AN. Flares of systemic lupus erythematosus during pregnancy and the puerperium: prevention, diagnosis and management. Expert review of clinical immunology. 2012; 8: 439-53. Lateef A and Petri M. Management of pregnancy in systemic lupus erythematosus. Nature reviews Rheumatology. 2012; 8: 710-8. Stanhope TJ, White WM, Moder KG, Smyth A and Garovic VD. Obstetric nephrology: lupus and lupus nephritis in pregnancy. Clinical journal of the American Society of Nephrology: CJASN. 2012; 7: 2089-99. Ateka-Barrutia O and Khamashta M. The challenge of pregnancy for patients with SLE. Lupus. 2013; 22: 1295-308. Clowse ME. Lupus activity in pregnancy. Rheumatic diseases clinics of North America. 2007; 33: 237-52, v. Petri M. Sex hormones and systemic lupus erythematosus. Lupus. 2008; 17: 412-5.
Objective. To examine humoral and cellular immune responses induced by a live attenuated herpes zoster (HZ) vaccine in patients with rheumatoid arthritis (RA) compared with osteoarthritis (OA) patients. Methods. This was an observational study of a live attenuated HZ vaccine in 41 patients with RA receiving conventional disease-modifying antirheumatic drugs (cDMARD) and/or low-dose glucocorticoids (GC) and in 28 patients with OA. Blood samples were obtained before and at 12 weeks after HZ vaccination. Immunogenicity was assessed using varicella zoster virus (VZV)-specific interferon gamma ELISA and an in-house ELISA. Clinical outcomes, including adverse events, HZ occurrence, and RA flares, were analyzed. Results. No patients developed vaccination-induced HZ during the followup period (median = 1.6 yrs). The HZ vaccine induced a significant increase in the VZV-specific enzyme-linked immunospot spot-forming units and anti-VZV immunoglobulin G antibodies in patients with RA and OA. The number of spot-forming units was lower in patients with RA than in patients with OA both at baseline and at 12 weeks after vaccination. The disease activity index for patients with RA was similar at baseline and at 12 weeks after vaccination. However, 6 patients with RA (14.6%) experienced a flare during the 12 weeks. Overall, 17 (24.6%) participants reported a mild adverse event such as an injection site reaction (11.6%). Conclusion. The HZ vaccine induced VZV-specific cellular and humoral responses in patients with RA. Although patients with RA showed a weaker vaccine-induced VZV-specific cellular immune response than patients with OA, the vaccine may be considered in patients with RA receiving cDMARD and/or low dose GC.
Interstitial lung disease (ILD) is a potentially serious yet underdiagnosed manifestation of primary Sjogren's syndrome (pSS).
Objectives
This observational study aimed to investigate the clinical, functional, and imaging characteristics of ILD in pSS, together with treatment and prognosis.
Methods
Longitudinal clinical and laboratory data of patients with pSS were extracted from three hospitals of the Catholic Medical Center through a clinical data warehouse, between March 1, 2012, and February 28, 2022. Predisposing factors for the development of ILD and acute exacerbation were identified using a logistic regression model.
Results
A total of 1,402 patients with pSS were included in this study (Female, 98%; median age, 55 years). Among them, 92 patients with pSS (7%) were comorbid with ILD (21 biopsy-proven cases). Fibrosing nonspecific interstitial pneumonia (NSIP) was the most prevalent CT pattern in pSS-ILD (58%), followed by usual interstitial pneumonia (20%), and organizing pneumonia (16%). At the diagnosis with pSS-ILD, 64% of patients showed reduced diffusion capacity, and 54.3% of patients with pSS-ILD showed a restrictive functional pattern. The median follow-up period was 3.2 years. During follow-up, six patients died (6.5%) and 26 patients (28.3%) experienced acute exacerbation (AE). However, 64% of patients showed no AE without treatment. Lower baseline forced vital capacity (FVC) (Odds ratio (OR), 0.962, P = 0.026) and high neutrophil-to-lymphocyte ratio (OR, 3.59, P = 0.046) were significant predisposing factors for AE.
Conclusion
ILD accounted for 7% of the comorbidity of SS, and 64% showed stable lung function without treatment. AE was associated with NLR and baseline FVC.
References
[1]Flament T, Bigot A, Chaigne B, Henique H, Diot E, Marchand-Adam S: Pulmonary manifestations of Sjögren's syndrome. Eur Respir Rev 2016, 25(140):110-123. [2]Mikolasch TA, George PM, Sahota J, Nancarrow T, Barratt SL, Woodhead FA et al. Multi-center evaluation of baseline neutrophil-to-lymphocyte (NLR) ratio as an independent predictor of mortality and clinical risk stratifier in idiopathic pulmonary fibrosis. EClinicalMedicine. 2022 Dec 1;55:101758. [3]Kim YJ, Choe J, Kim HJ, Song JW. Long-term clinical course and outcome in patients with primary Sjogren syndrome-associated interstitial lung disease. Sci Rep. 2021;11(1):12827.
Antibodies against citrullinated peptides are specific to rheumatoid arthritis (RA), although its pathologic relevance has not been clearly understood.
Objectives
This study was undertaken to develop a novel anti-citrullinated petide antibody (ACPA) and to investigate the arthritogenecity of the ACPA in collagen-induced arthritis (CIA) model, the commonly used murine model of RA.
Methods
The novel ACPA, 12G1 was developed by injecting cyclic citrullinated antigen to mice and subsequently hybridizing the B cells producing citrullinated peptide-specific antibodies with myeloma cell line. Arthritic joints of mice with CIA and collagen antibody induced arthritis (CAIA) and IL-1Ra knockout mice underwent immunohistochemical staining with 12G1 antibody, and the staining pattern was compared. Confocal immunostaining was used to identify co-localization of 12G1 with various citrullinated peptides. 12G1 in the presence or absence of chelating bead was administered to mice with CIA on day 21 and 28 after type II collagen (CII) immunization to investigate the arthritogenecity of 12G1.
Results
12G1 could detect citrullinated peptides in the arthritic joints of various experimental arthritis models. On confocal immunostaining of arthritic joints with 12G1, it was found to be co-localized with well-known citrullintaed peptides including vimentin, collagen, anti-immunoglobulin binding protein (BiP), and fibronectin. There was no difference in the staining pattern of citrullinated peptides between the different arthritis models. The injection 12G1 apparently showed comparable effect of a booster immunization in CIA mice with single immunization of CII, which was abolished when 12G1 was injected with chelating beads.
Conclusions
The novel ACPA, 12G1 identified various citrullinated peptides in the arthritic joints of various experimental arthritis models. 12G1-treated mice develop arthritis with single immunization of CII, which suggested arthritogenic potential of ACPA in CIA mice.
References
Sakkas, L. I., et al. (2014). Anti-citrullinated peptides as autoantigens in rheumatoid arthritis-relevance to treatment. Autoimmun Rev 13(11): 1114-1120. Vossenaar, E. R., et al. (2003). Citrullination of synovial proteins in murine models of rheumatoid arthritis. Arthritis Rheum 48(9): 2489-2500.
To investigate clinical characteristics of patients with primary Sjögren's syndrome (SS) who were negative for anti-Ro/SSA antibody but positive for minor salivary gland biopsy (MSGB) compared to patients who presented positivity for anti-Ro/SSA antibody.The data of 355 patients from the Korean Initiative of primary Sjögren's Syndrome (KISS), a nationwide prospective cohort for primary SS in Korea, were analysed. All patients fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) classification criteria. Of these patients, 326 were positive for anti-Ro/SSA antibody and 29 were antibody-negative, although they had positive findings in MSGB. Various clinical features including all kinds of tests for evaluating secretory function, disease-related clinical indices and serological values available in the cohort were compared between the two groups.The anti-Ro/SSA-negative group showed less rheumatoid factor positivity (p<0.001), leucopenia (p=0.003), hyper-gammaglobulinaemia (p<0.001), lower serum β2-microglobulin level (p=0.034), more anti-centromere antibody positivity (p<0.001), higher score in dryness domain of EULAR SS patient-reported index (p=0.048) and more positivity for peripheral nervous system domain in EULAR SS disease activity index and loss of teeth in SS disease damage index (p=0.021 and 0.041, respectively) than patients who were positive for anti-Ro/ SSA antibody.Primary SS patients who are negative for anti-Ro/SSA antibody have different clinical characteristics compared to patients who are positive for such antibody in Korea. Therefore, clinicians should consider MSGB in patients with suspicious symptoms who are anti-Ro/SSA-negative.
All-trans-retinoic acid (RA) and all-trans-retinol (ROL) are not widely used as anti-wrinkle agents due to their irritancy and photo-stability, respectively. Therefore, the safety and photo-stability in the development of RA or ROL derivatives have been an important issue.To identify the efficacy of retinyl retinoate as an anti-aging agent of cosmetics in treating females over 30 years old with periorbital wrinkles.The clinical study was a prospective, double-blind, randomized, and controlled study with a total of 11 Korean women. At every 4 weeks, the effectiveness was assessed with a global photodamage score, photographs, and image analysis using replicas and visiometers. The dermal distance and intensity was also evaluated using Dermascan C.A statistically significant improvement in facial wrinkles (P<0.05) in eleven volunteers was observed in a clinical trial. The successive application of 0.06% retinyl retinoate cream for 3 months showed decreased depth and area of wrinkles in comparison with 0.075% retinol cream. The visual wrinkle improvement and the maximum roughness improvement rate (R2) for retinyl retinoate cream were 22% higher than that of retinol cream after 12 weeks. A statistically significant increase was observed after 8 and 4 weeks for dermal distance and dermal intensity, respectively (P<0.05).Retinyl retinoate had characteristic features of new anti-aging agents, and effectively improved facial wrinkle conditions.
Interferon (IFN) signatures are upregulated in patients with primary Sjogren9s syndrome (pSS) and interferons are considered to play a pathogenic role in pSS. Therefore, Janus kinase (JAK) which mediates interferon signaling pathway may be a good therapeutic target
Objectives
We set out to investigate whether a selective JAK1 inhibitor, filgotinib would ameliorate disease-related parameters in non-obese diabetic (NOD) mice, an animal model SS
Methods
Filgotinib (1.5mg/kg) or vehicle (saline) was intraperitoneally injected three times per week from 8 weeks after birth. Salivary flow rate (SFR) was addressed on 8, 12, 16 and 20 weeks. Histologic analysis was performed on 20 weeks. The effect of filgotinib on the expressions of B cell activating factor (BAFF) and chemokines (CXCL10 [IP-10], CXCL3 [fractalkine], CCL-2 [MCP-1]) in human salivary gland epithelial cell (SGEC) line or primary epithelial cells of patients with pSS was determined in vitro.
Results
The SFR of NOD mice in both groups decreased over time. Of note, SFRs of filgotinib-treated mice were greater than those of controls. Histologic evaluation of the salivary gland revealed that the lymphocytic infiltration of salivary gland was markedly reduced in the mice treated with filgotinib. Filgotinib suppressed STAT1 phosphorylation in IFN-treated SGECs. In addition, IFN-induced BAFF and chemokine production of SGECs or primary epithelial cells were abrogated by filgotinib treatment.
Conclusions
Filgotinib suppresses SFR decrease and lymphocytic infiltration of salivary glands of NOD mice by inhibiting inhibiting IFN signaling pathway, thus suppressing BAFF and chemokine production of salivary gland epithelial cells. JAK inhibition may be a novel therapeutic approach for SS.
Rheumatoid arthritis (RA) is closely associated with the oral and gut microbiomes. Fungal cell wall components initiate inflammatory arthritis in mouse models. However, little is known regarding the role of the fungal community in the pathogenesis of RA. To evaluate the association between RA and the gut microbiome, investigations of bacterial and fungal communities in patients with RA are necessary. Therefore, we investigated the compositions and associations of fecal bacterial and fungal communities in 30 healthy controls and 99 patients with RA. The relative abundances of Bifidobacterium and Blautia decreased, whereas the relative abundance of Streptococcus increased, in patients with RA. The relative abundance of Candida in the fecal fungal community was higher in patients with RA than in healthy controls, while the relative abundance of Aspergillus was higher in healthy controls than in patients with RA. Candida species-specific gene amplification showed that C. albicans was the most abundant species of Candida. Ordination analysis and random forest classification models supported the findings of structural changes in bacterial and fungal communities. Aspergillus was the core fecal fungal genus in healthy controls, although Saccharomyces spp. are typically predominant in Western cohorts. In addition, bacterial–fungal association analyses showed that the hub node had shifted from fungi to bacteria in patients with RA. The finding of fungal dysbiosis in patients with RA suggests that fungi play critical roles in the fecal microbial communities and pathogenesis of RA.
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