Discriminating between Homogeneous (AC-1) and Dense Fine Speckled (AC-2) Antinuclear Antibody Patterns: Re-Evaluation of Immunofluorescence Imaging.

Antinuclear antibodies (ANAs) are essential diagnostic markers in systemic autoimmune rheumatic diseases. Among the 30 ANA patterns, homogeneous (AC-1) and dense fine speckled (AC-2) should be focused on owing to their somewhat indistinct presentation in immunofluorescence imaging and distinct correlation with clinical conditions. This study aimed to develop a flowchart to guide discrimination between AC-1 and AC-2 patterns and to re-evaluate ANA samples according to this flowchart to verify its detection ability. We re-evaluated immunofluorescence imaging of 62 ANA blood samples simultaneously subjected to solid-phase assays for autoantibodies against dsDNA, nucleosomes, histones, and DFS70. The results showed statistically significant odd ratios (ORs) of detection of anti-DFS70 using AC-2 after re-evaluation of total samples (OR 101.9, 95% CI 11.7-886.4, p-value < 0.001) and subgroup analysis of patients' samples (OR 53.8, 95% CI 5.9-493.6, p-value < 0.001). The OR of anti-nucleosome/histone/dsDNA detection using AC-1 in re-evaluated data increased to 5.43 (95% CI 1.00-29.61, p-value = 0.05). In the analysis of specific autoantibodies, more than half of the samples with an AC-2 pattern (54.2%) had specific autoantibodies other than anti-DFS70. We conclude that the flowchart for discriminating between AC-1 and AC-2 ANA patterns in this study is a viable practical guide for other laboratories when encountering equivocal ANA results.

Finding the Common Single-Nucleotide Polymorphisms in Three Autoimmune Diseases and Exploring Their Bio-Function by Using a Reporter Assay.

In clinical practice, it is found that autoimmune thyroid disease often additionally occurs with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In addition, several studies showed that eye-specific autoimmune diseases may have a strong relationship with systemic autoimmune diseases. We focused on Graves' disease (GD) with ocular conditions, also known as Graves' ophthalmopathy (GO), trying to find out the potential genetic background related to GO, RA, and SLE. There were 40 GO cases and 40 healthy controls enrolled in this study. The association between single-nucleotide polymorphisms (SNPs) of the co-stimulatory molecule genes and GO was analyzed using a chi-square test. It showed that rs11571315, rs733618, rs4553808, rs11571316, rs16840252, and rs11571319 of CTLA4, rs3181098 of CD28, rs36084323 and rs10204525 of PDCD1, and rs11889352 and rs4675379 of ICOS were significantly associated with GO based on genotype analysis and/or allele analysis (p < 0.05). After summarizing the GO data and the previously published SLE and RA data, it was found that rs11571315, rs733618, rs4553808, rs16840252, rs11571319, and rs36084323 were shared in these three diseases. Furthermore, the bio-function was confirmed by dual-luciferase reporter assay. It was shown that rs733618 T > C and rs4553808 A > G significantly decreased the transcriptional activity (both p < 0.001). This study is the first to confirm that these three diseases share genetically predisposing factors, and our results support the proposal that rs733618 T > C and rs4553808 A > G have bio-functional effects on the transcriptional activity of the CTLA4 gene.

The effect of uveitis and undiagnosed spondyloarthritis: a systematic review and meta-analysis.

Delay diagnosis of spondyloarthritis (SpA) is associated with poor functional ability and quality of life. Uveitis is the most frequent extraarticular manifestation in SpA, and its prevalence increases with longer disease duration. This study examines the effect of uveitis on the disease activity and functional outcome of undiagnosed SpA. We reviewed published and unpublished studies. Data were pooled using the random-effects model; pooled means, and mean differences (MDs) were calculated. In the included 14 studies, disease activity, functional index, and inflammatory markers were measured in 2581 patients with SpA with uveitis and 13,972 without. The pooled mean delay in diagnosis of SpA with uveitis (6.08 years; 95% CI 4.77 to 7.38) was longer than those without (5.41 years; 95% CI 3.94 to 6.89). The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was the highest for a delay of 2-5 years (5.60, 95% CI 5.47 to 5.73) and the Bath Ankylosing Spondylitis Functional Index (BASFI) score was the lowest for a delay of < 2 years (2.92, 95% CI 2.48 to 3.37) and gradually increased to delay of > 10 years (4.17, 95% CI 2.93 to 5.41). Patients with SpA with uveitis had higher trend of Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP and BASDAI. The delay to diagnosis was longer in SpA with uveitis, and disease activity was often higher than those without uveitis. Early diagnosis of SpA with timely initiation of an appropriate management plan may reduce the adverse effects of the disease and improve functional ability.

COVID-19-related disruptions in implementation of a randomized control trial: An autoethnographic report.

BACKGROUND AND AIMS: The SARS-Cov-2 virus (COVID-19) has not only threatened the health of the world's population but also presented challenges for conducting human subject research studies. Although many institutions have now established guidelines for conducting research during the COVID-19 pandemic, reports of the practical experiences of researchers are limited. This report presents the challenges nurse researchers encountered when conducting a randomized controlled trial to develop an arthritis self-management application during the COVID-19 pandemic in Taiwan and how researchers responded to the challenges. METHODS: Qualitative data from five nurse researchers were collected from August 2020 to July 2022 at a rheumatology clinic in northern Taiwan. This collaborative autoethnographic report was drawn from data comprised of detailed field notes and weekly discussions regarding research challenges we were confronting. Data were analyzed to determine successful strategies employed to overcome the challenges and allow for completion of the study. RESULTS: Minimizing the risk of exposure to the virus for researchers and participants resulted in four major challenges to conducting our research: patient screening and recruitment, delivery of the intervention, obtaining follow-up data, and unanticipated budget increases. CONCLUSIONS: Challenges reduced sample size, altered intervention delivery, increased time and money beyond what was originally budgeted, and delayed completion of the study. Adapting to a new healthcare environment required flexibility for recruitment, alternate means of providing intervention instructions, and an awareness of disparities in participants' internet proficiency. Our experiences can serve as an example for other institutions and researchers faced with similar challenges.

Exploration of the association between the single-nucleotide polymorphism of co-stimulatory system and rheumatoid arthritis.

Introduction: The human leukocyte antigen (HLA) has been linked to the majority of autoimmune diseases (ADs). However, non-HLA genes may be risk factors for ADs. A number of genes encoding proteins involved in regulating T-cell and B-cell function have been identified as rheumatoid arthritis (RA) susceptibility genes. Methods: In this study, we investigated the association between RA and single-nucleotide polymorphisms (SNPs) of co-stimulatory or co-inhibitory molecules in 124 RA cases and 100 healthy controls without immune-related diseases [including tumor necrosis factor superfamily member 4 (TNFSF4), CD28, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and programmed cell death protein 1 (PDCD1)]. Results: The results showed that there were 13 SNPs associated with RA, including rs181758110 of TNFSF4 (CC vs. CT, p = 0.038); rs3181096 of CD28 (TT vs. CC + CT, p = 0.035; CC vs. TT, p = 0.047); rs11571315 (TT vs. CT, p = 0.045), rs733618 (CC vs. TT + CT, p = 0.043), rs4553808 (AA vs. AG vs. GG, p = 0.035), rs11571316 (GG vs. AG vs. AA, p = 0.048; GG vs. AG + AA, p = 0.026; GG vs. AG, p = 0.014), rs16840252 (CC vs. CT vs. TT, p = 0.007; CC vs. CT, p = 0.011), rs5742909 (CC vs. CT vs. TT, p = 0.040), and rs11571319 of CTLA4 (GG vs. AG vs. AA, p < 0.001; GG vs. AG + AA, p = 0.048; AA vs. GG + AG, p = 0.001; GG vs. AA, p = 0.008; GG vs. AG, p ≤ 0.001); and rs10204525 (TT vs. CT + CC, p = 0.024; TT vs. CT, p = 0.021), rs2227982 (AA vs. GG, p = 0.047), rs36084323 (TT vs. CT vs. CC, p = 0.022; TT vs. CT + CC, p = 0.013; CC vs. TT + CT, p = 0.048; TT vs. CC, p = 0.008), and rs5839828 of PDCD1 (DEL vs. DEL/G vs. GG, p = 0.014; DEL vs. DEL/G + GG, p = 0.014; GG vs. DEL + DEL/G, p = 0.025; DEL vs. GG, p = 0.007). Discussion: Consequently, these SNPs may play an important role in immune regulation, and further research into the role of these SNPs of immune regulatory genes in the pathogenesis of RA is required.

Long-Term Survival of Patients with Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Single-Center Cohort.

Pulmonary arterial hypertension (PAH) is a rare but severe complication of connective tissue disease (CTD). CTD-associated PAH (CTD-PAH) is the most common subgroup of PAH in East Asia. We prospectively collected 41 patients with CTD-PAH and followed them for a mean period of 43 ± 36 months. The long-term survival rates of the CTD-PAH patients at 1, 2, 3 and 5 years were 90%, 80%, 77%, and 60%, respectively. The non-survivors had more dilated main pulmonary arteries, higher pulmonary artery pressure and pulmonary vascular resistance (PVR). PAH-specific therapy resulted in improvements in functional class, 6-minute walk distance, serum uric acid, right ventricular function and PVR. Increased C-reactive protein during follow-up, indicating inflammatory processes, was also crucial for the management of CTD-PAH. Therefore targeting both PAH and inflammation is important in this specific subgroup of PAH. The results of this study may help develop treatment strategies for CTD-PAH patients.

Coexisting Nodular Sclerosis Hodgkin Lymphoma and Kimura's Disease: A Case Report and Literature Review.

Kimura's disease (KD) is a rare lymphoproliferative fibroinflammatory disorder that commonly affects the subcutaneous tissue and lymph nodes of the head and neck. The condition is a reactive process involving T helper type 2 cytokines. Concurrent malignancies have not been described. Differential diagnosis with lymphoma can be challenging without tissue biopsy. Here, we present the first reported case of coexisting KD and eosinophilic nodular sclerosis Hodgkin lymphoma of the right cervical lymphatics in a 72-year-old Taiwanese man.

DNA methylation of ITGB2 contributes to allopurinol hypersensitivity.

BACKGROUNDS: HLA-B*58:01 allele was strongly associated with allopurinol induced severe cutaneous adverse drug reaction (SCAR). However, HLA-B genotype is not sufficient to predict the occurrence of allopurinol-induced SCAR. OBJECTIVE: To discover DNA methylation markers for allopurinol-induced SCAR which may improve the prediction accuracy of genetic testing. STUDY DESIGN: The study was designed as a retrospective case-control clinical study in multicenter hospitals across Taiwan, Mainland China, Malaysia and Canada. 125 cases of allopurinol-induced SCAR patients and 139 cases of allopurinol tolerant controls were enrolled in this study during 2005 to 2021. RESULTS: The results of genome-wide DNA methylation assay of 62 patients revealed that ITGB2 showed strong discriminative ability of allopurinol-induced SCAR in both HLA-B*58:01 positive and negative patients with AUC value of 0.9364 (95% CI 0.8682-1.000). In validation study, significant hypermethylation of ITGB2 were further validated in allopurinol-induced SCAR patients compared to tolerant controls, especially in those without HLA-B*58:01(AUC value of 0.8814 (95% CI 0.7121-1.000)). Additionally, the methylation levels of 2 sites on ITGB2 were associated with SCAR phenotypes. Combination of HLA-B*58:01 genotyping and ITGB2 methylation status could improve the prediction accuracy of allopurinol-induced SCAR with the AUC value up to 0.9387 (95% CI 0.9089-0.9684), while the AUC value of HLA-B*58:01 genotyping alone was 0.8557 (95% CI 0.8030-0.9083). CONCLUSIONS: Our study uncovers differentially methylated genes between allopurinol-induced SCAR patients and tolerant controls with positive or negative HLA-B*58:01 allele and provides the novel epigenetic marker that improves the prediction accuracy of genetic testing for prevention of allopurinol-induced SCAR.

Fetal-neonatal and maternal outcomes in women with Sjögren syndrome: a population-based registry linkage study.

OBJECTIVE: To provide better preconceptional and prenatal counselling to patients with sjögren syndrome (SS). METHODS: In total, 2 100 143 pregnancies between 2004 and 2014 were identified in the Taiwan National Health Insurance database and birth registry. The maternal history of SS was ascertained, and data were compared between pregnant women with and without SS. We assessed the odds ratios and 95% CIs of fetal-neonatal and maternal outcomes. RESULTS: There were 449 pregnancies in women with SS and 2 099 694 pregnancies in women without SS. The risks of still birth [odds ratio (OR) = 2.14, 95% CI = 1.01, 4.55], low birth weight (<2500 g, OR = 2.53, 95% CI = 1.92, 3.33), small for gestational age (OR = 2.03, 95% CI = 1.57, 2.03) and fetal distress (OR = 1.72, 95% CI = 1.2, 2.45) as well as maternal risks of pulmonary oedema (OR = 11.64, 95% CI = 1.62, 83.48), shock (OR = 6.07, 95% CI = 1.51, 24.3) and respiratory distress (OR = 5.61, 95% CI = 1.39, 22.6) were higher in the SS group than in the non-SS group. CONCLUSION: Women with SS have significant risks of adverse fetal-neonatal and maternal outcomes and must undergo prenatal counselling to understand the risks involved before conception.

Clinical and serological factors associated with lupus pericarditis: a case-control study.

OBJECTIVE: Lupus pericarditis, a common manifestation of systemic lupus erythematosus (SLE), can be fatal. We examined the prevalence of lupus pericarditis and its associated factors in a Taiwanese SLE cohort. METHODS: Patients with SLE treated at Change Gung Memorial Hospital between January 2005 and December 2012 were included, and their age, sex, SLE disease duration, SLE disease activity index (SLEDAI) score, laboratory test results, comorbidities, and treatment regimen were noted. Factors related to lupus pericarditis were examined using univariate and multivariate logistic regression analyses. RESULTS: Of the 689 patients, 88.7% were women; age at diagnosis (± standard deviation (SD)) was 40.78 ± 15.59 years, and disease duration at study entry was 11.93 ± 8.21 years. The prevalence of lupus pericarditis was 16.4% (n = 113). Notably, older age at diagnosis (p = 0.0165), longer disease duration (p = 0.009), higher SLEDAI score (p < 0.0001), renal disorder (p = 0.003), lymphocytopenia (p < 0.0001), thrombocytopenia (p = 0.004), and anti-phospholipid antibody (aPL) seropositivity (p = 0.002) were significantly associated with lupus pericarditis. In multivariate analysis, adjusted for sex, SLE disease duration, age, and SLEDAI score, patients with lymphocytopenia and aPL seropositivity were related to a twofold (odds ratio (OR) 2.015, 95% confidence interval (CI) 1.091-3.858) and 1.5-fold (OR 1.569, 95% CI 1.017-2.421) greater prevalence of lupus pericarditis, respectively. CONCLUSIONS: Lupus pericarditis occurred in approximately one fifth of patients in this cohort. Patients with SLE with lymphocytopenia or anti-phospholipid antibody seropositivity were associated with a higher rate of lupus pericarditis. Key Points • Lupus pericarditis is a common manifestation of SLE that occurred in one-fifth patients in this study. • Lymphocytopenia and aPL antibody seropositivity are associated with a higher likelihood of developing lupus pericarditis. • Patients with lupus pericarditis should be identify early and treated with caution to prevent further morbidity and mortality.

The susceptibility of single nucleotide polymorphisms located within co-stimulatory pathways to systemic lupus erythematosus.

Introduction: Autoimmune diseases result from the loss of immune tolerance, and they exhibit complex pathogenic mechanisms that remain challenging to effectively treat. It has been reported that the altered expression levels of co-stimulatory/inhibitory molecules will affect the level of T/B cell activation and lead to the loss of immune tolerance. Methods: In this study, we evaluated the gene polymorphisms of the ligand genes corresponding co-stimulatory system that were expressed on antigen-presenting cells (CD80, CD86, ICOSLG, and PDL1) from 60 systemic lupus erythematosus (SLE) patients and 60 healthy controls. Results: The results showed that rs16829984 and rs57271503 of the CD80 gene and rs4143815 of the PDL1 gene were associated with SLE, in which the G-allele of rs16829984 (p=0.022), the A-allele of rs57271503 (p=0.029), and the GG and GC genotype of rs4143815 (p=0.039) may be risk polymorphisms for SLE. Discussion: These SNPs are in the promoter and 3'UTR of the genes, so they may affect the transcription and translation activity of the genes, thereby regulating immune function and contributing to the development of SLE.

Investigation of the association between the genetic polymorphisms of the co-stimulatory system and systemic lupus erythematosus.

Human leukocyte antigen genes have been shown to have the strongest association with autoimmune disease (AD). However, non-HLA genes would be risk factors of AD. Many genes encoding proteins that are related to T- and B-cell function have been identified as susceptibility genes of systemic lupus erythematosus (SLE). In this study, we explored the correlation between SLE and the genetic polymorphisms of co-stimulatory/co-inhibitory molecules, including CTLA4, CD28, ICOS, PDCD1, and TNFSF4. We found that there were nine single-nucleotide polymorphisms (SNPs) associated with SLE, namely, rs11571315 (TT vs. CT vs. CC: p < 0.001; TT vs. CT: p = 0.001; p = 0.005; TT vs. CT +CC: p < 0.001; TT+CT vs. CC: p = 0.032), rs733618 (CC vs. CT vs. TT: p = 0.002; CC vs. CT: p = 0.001; CC vs. TT: p = 0.018; CC vs. CT + TT: p = 0.001), rs4553808 (AA vs. AG: p < 0.001), rs62182595 (GG vs. AG vs. AA: p < 0.001; GG vs. AG: p < 0.001; GG vs. AG+AA: p < 0.001), rs16840252 (CC vs. CT vs. TT: p < 0.001; CC vs. CT: p < 0.001; CC vs. CT + TT: p < 0.001), rs5742909 (CC vs. CT: p = 0.027; CC vs. CT + TT: p = 0.044), rs11571319 (GG vs. AG vs. AA: p < 0.001, GG vs. AG: p < 0.001; GG vs. AG+AA: p < 0.001), rs36084323 (CC vs. CT vs. TT: p = 0.013, CC vs. TT: p = 0.004; CC vs. CT + TT: p = 0.015; CC +CT vs. TT: p = 0.015), and rs1234314 (CC vs. CG vs. GG: p = 0.005; GG vs. CC: p = 0.004; GG+ CG vs. CC: p = 0.001), but not in CD28 and ICOS by using the chi-square test. Additionally, rs62182595 and rs16840252 of CTLA and rs1234314 and rs45454293 of TNFSF4 were also associated with SLE in haplotypes. These SLE-related SNPs also had an association with several diseases. It was indicated that these SNPs may play an important role in immune regulation and pathogenic mechanisms.

Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures.

OBJECTIVES: Observational studies have demonstrated associations between gout and hypertension, but whether they are causal remains unclear. Our work aims to assess the causal relationship between gout and hypertension. METHODS: We obtained genetic information from the Taiwan Biobank, including 88,347 participants and 686,439 single-nucleotide polymorphisms (SNPs). A novel model of Mendelian randomisation (MR) with coarsened exposures was used to examine the causality between the liability of gout on hypertension and vice versa, using 4 SNPs associated with gout and 10 SNPs associated with hypertension after removal of SNPs associated with measured confounders. The binary exposure (gout/hypertension) can be considered a coarsened approximation of a latent continuous trait. The inverse-variance weighted (IVW) and polygenic risk score (PRS) methods were used to estimate effect size. The MR analysis with coarsened exposures was performed with and without adjustments for covariates. RESULTS: Of the 88,347 participants, 3253 (3.68%) had gout and 11,948 (13.52%) had hypertension (men, 31.9%; mean age 51.1 [SD, 11.1] years). After adjusting to measured confounders, MR analysis with coarsened exposures showed a significant positive causal effect of the liability of gout on hypertension in both the IVW method (relative risk [RR], 1.10; 95% confidence interval [CI], 1.03-1.19; p = 0.0077) and the PRS method (RR, 1.10; 95% CI, 1.02-1.19; p = 0.0092). The result of causality was the same before and after involving measured confounders. However, there was no causal effect of the liability of hypertension on gout. CONCLUSIONS: In this study, we showed that the liability of gout has a causal effect on hypertension, but the liability of hypertension does not have a causal effect on gout. Adequate management of gout may reduce the risk of developing hypertension.

Implementation of NUDT15 Genotyping to Prevent Azathioprine-Induced Leukopenia for Patients With Autoimmune Disorders in Chinese Population.

Azathioprine (AZA) is commonly used for many autoimmune disorders; however, the limitation of its clinical use is due to potential toxicities, including severe leukopenia. Recent studies have identified genetic NUDT15 variants strongly associated with AZA-induced leukopenia in Asian patients. This study aimed to investigate the strength of above genetic association and evaluate the usefulness of prospective screening of the NUDT15 variants to prevent AZA-induced leukopenia in Chinese patients. AZA-induced leukopenia in patients with autoimmune disorders were enrolled from multiple medical centers in Taiwan/China between 2012 and 2017 to determine the strength of genetic association of NUDT15 or TPMT variants by whole exome sequencing (WES). Furthermore, a prospective study was conducted between 2018 and 2021 to investigate the incidence of AZA-induced leukopenia with and without genetic screening. The WES result showed the genetic variants of NUDT15 R139C (rs116855232) (P = 3.7 × 10-25 , odds ratio (OR) = 21.7, 95% confidence interval (95% CI) = 12.1-38.8) and NUDT15 rs746071566 (P = 4.2 × 10-9 , OR = 7.1, 95% CI = 3.7-13.7), but not TPMT, were associated with AZA-induced leukopenia and NUDT15 R139C variant shows the highest sensitivity with 92.5%. Furthermore, the targeted screening of 1,013 participants for NUDT15 R139C enabled those identified as carriers to use alternative immunosuppressants. This strategy resulted in a significant decrease in the incidence of AZA-induced leukopenia compared with historical incidence (incidence rate = from 7.6% decreased to 0.4%; P = 9.3 × 10-20 ). In conclusion, the NUDT15 R139C variant was strongly associated with AZA-induced leukopenia in Chinese patients. The genetic screening of NUDT15 R139C followed by use of alternative immunosuppressants in identified carriers effectively decreased the incidence of AZA leukopenia for patients with autoimmune disorders.

Consensus recommendations on managing the selected comorbidities including cardiovascular disease, osteoporosis, and interstitial lung disease in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA)-related comorbidities, including cardiovascular disease (CVD), osteoporosis (OP), and interstitial lung disease (ILD), are sub-optimally managed. RA-related comorbidities affect disease control and lead to impairment in quality of life. We aimed to develop consensus recommendations for managing RA-related comorbidities. METHODS: The consensus statements were formulated based on emerging evidence during a face-to-face meeting of Taiwan rheumatology experts and modified through three-round Delphi exercises. The quality of evidence and strength of recommendation of each statement were graded after a literature review, followed by voting for agreement. Through a review of English-language literature, we focused on the existing evidence of management of RA-related comorbidities. RESULTS: Based on experts' consensus, eleven recommendations were developed. CVD risk should be assessed in patients at RA diagnosis, once every 5 years, and at changes in DMARDs therapy. Considering the detrimental effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids on CVD risks, we recommend using the lowest possible dose of corticosteroids and prescribing NSAIDs cautiously. The OP/fragility fracture risk assessment includes dual-energy X-ray absorptiometry and fracture risk assessment (FRAX) in RA. The FRAX-based approach with intervention threshold is a useful strategy for managing OP. RA-ILD assessment includes risk factors, pulmonary function tests, HRCT imaging and a multidisciplinary decision approach to determine RA-ILD severity. A treat-to-target strategy would limit RA-related comorbidities. CONCLUSIONS: These consensus statements emphasize that adequate control of disease activity and the risk factors are needed for managing RA-related comorbidities, and may provide useful recommendations for rheumatologists on managing RA-related comorbidities.

Diagnostic Utility of Serum IgG4 in Autoimmune Pancreatitis: An Updated Comprehensive Systematic Review and Meta-analysis.

OBJECTIVES: Despite many studies suggesting an association between serum immunoglobulin G4 (sIgG4) and autoimmune pancreatitis (AIP), the evidence of utility in differentiation between AIP and pancreatic cancer (PC) remain uncertain. METHODS: The analysis based on published studies. Data were pooled by means of a random-effects model, and sensitivity, specificity, diagnostic odds ratios (DOR), areas under summary receiver operating characteristic curves were calculated. RESULTS: In the included thirteen studies, sIgG4 were measured in 594 patients with AIP and 958 patients with PC. The pooled sensitivity, specificity, DOR, and area under the curve were 0.72 [95% confidence interval (CI): 0.68-0.75], 0.93 (95% CI: 0.92-0.95), 51.37 (95% CI: 23.20-113.74), and 0.91 (95% CI: 0.87-0.95). Subgroup analyses of the DORs for region and year: Asia, (112.10; 95% CI: 27.72-453.32), non-Asia (26.01; 95% CI: 12.38-54.65), and year before 2011 (107.61; 95% CI: 39.30-294.68), year after 2011 (26.96; 95% CI: 9.78-74.32). Overall, sIgG4 was associated with AIP, the result revealed a moderate sensitivity 0.72 and high specificity 0.93. In the meta-analysis, the pooled DOR of sIgG4 levels of 2-fold upper limit 50.44 was similar with the DOR 51.37 when 1-fold cut-off value, but the summary receiver operating characteristic was 0.755 and 0.91. The higher specificity (from 93% to 98%) derived from the cut-off value (from 130-140 to 260-280 mg/dL) for sIgG4 occurred at a significant reduction in sensitivity (from 72% to 43%). CONCLUSIONS: The study revealed sIgG4 is a good marker of AIP. Screening of sIgG4 may help clinicians differentiate between AIP and PC, and the best cut-off value should be 140 rather than 280 mg/dL.

It Is Like a Puppet Show-Experiences of Rheumatoid Arthritis Among Adult Chinese: A Qualitative Study.

Rheumatoid arthritis results in progressive destruction of the joints. However, descriptions of patient's experiences with the disease are limited. This qualitative study aimed to explore patients' personal experiences with rheumatoid arthritis in Taiwan. Face-to-face interviews were conducted with 30 patients from January to May 2019; interview data were analyzed with content analysis. Most participants were female (90%); their mean age was 57 years. Three main categories emerged from analysis of the data: "physical suffering," "limitations of abilities," and "coexisting with the disease." Physical suffering was due to personal lifelong hardships from chronic pain and stiffness. Limitations of abilities occurred from loss of physical function and limited social life, due to participants discomfort with joint deformities and their appearance to others. Participants coexisted with the disease by making changes in their outlook and comparing their lives with others in order to gain a positive perspective.

Expectations of an Online-Self-Management Program for Rheumatoid Arthritis.

This qualitative descriptive study aimed to explore expectations of patients and healthcare experts for an online self-management program for rheumatoid arthritis. Participants were recruited from rheumatology clinics, medical centers, and universities in Taiwan. Individual face-to-face, semi-structured interviews were conducted with patients (n = 16) and healthcare experts (n = 7). Content analysis of the interview data resulted in five subthemes for expectations of an online self-management program: information about how the disease trajectory would impact future health status, availability of opportunities for self-monitoring, opportunities to interact with fellow patients and healthcare providers, simplicity and ease-of-use of the program, and methods to facilitate patient-motivation. These subthemes formulated two overarching themes: content and format. An online self-management program for patients with rheumatoid arthritis should provide evidence-based information about disease variables and behaviors aligned with the specific needs of the individual and adopt strategies that encourage and increase motivation and confidence.

Corrigendum: Investigation of the association between the genetic polymorphisms of co-stimulatory system and systemic lupus erythematosus.

[This corrects the article DOI: 10.3389/fimmu.2022.946456.].

Kimura's disease: A clinicopathological study of 23 cases.

Introduction: Kimura's disease (KD) is an uncommon lymphoproliferative fibroinflammatory disorder. Patients present with head and neck subcutaneous nodules with or without lymphadenopathy. Peripheral blood eosinophilia and elevated serum immunoglobulin E (IgE) levels are typical. This study was designed to delineate the clinicopathological features, pattern of care, and disease course of 23 Taiwanese patients with KD. Methods: We retrospectively analyzed the clinical data of 23 consecutive cases (16 male and 7 female; age at diagnosis: 12-77 years) of KD diagnosed at our institution from 2015 to 2020. Results: The median time from presentation to diagnosis was 1 month. Twenty-one patients presented with unilateral or bilateral head and neck masses. The remaining two presented with right flank and right arm lesions, respectively. Peripheral blood eosinophilia was observed in nine, and elevated IgE levels were observed in four. All were diagnosed using either excisional or core-needle biopsy. Seven patients underwent fine needle aspiration without a diagnostic yield. Salivary gland and lymph node involvement was observed in three and seven patients, respectively. Most lesions showed tissue eosinophilia (100%) and florid follicular hyperplasia (78.26%). Three cases had histological KD-IgG4-RD overlap and three had comorbid IgG4-RD were recognized. Thirteen patients underwent surgical resection, one received adjuvant therapy, and two received prednisolone monotherapy. Conclusion: KD should be considered in patients with subcutaneous masses, eosinophilia, and elevated IgE levels. Biopsy remains the gold standard of diagnosis. Increased recruitment of IgG4+ plasma cells is a common feature. Consideration of IgG4-RD in all KD patients may be prudent.