Myositis autoantibodies detected by line blot immunoassay: clinical associations and correlation with antibody signal intensity.

The aim of this study is to assess the relationship between myositis specific (MSA) and myositis associated (MAA) antibodies and diagnosis (including idiopathic inflammatory myopathies [IIM] and other systemic autoimmune diseases [SAID]), and to explore the impact of antibody signal intensity in diagnostic accuracy. We retrospectively reviewed all the serum samples obtained from patients tested for MSA/MAA by line immunoassay (LIA) between 01/01/2018 and 31/12/2020 in Ramón y Cajal University Hospital (Spain). Clinical true positive (CTP) MSAs and MAAs were defined as those patients with IIM or SAID with phenotypes expected of that MSA/MAA. Patients who did not have a phenotype compatible with that antibody were classified as clinical false positive (CFP). One hundred and thirty positive samples were analysed. Forty-six patients (33.38%) were classified as IIM, forty-two (32.3%) as SAID and forty-two (32.3%) as non-IIM/SAID. Among these 130 patients, 164 MSA/MAA were detected. Eighty-five (51.8%) positive MSA/MAA were classified as CTP, and seventy-nine (48.2%) as CFP. Strongly positive antibodies were more frequently CTP (35/47, 74.5%) than weak positives (54/68, 36.8%), (p ˂ 0.001). Antibodies classified as CTP had a higher signal intensity than CFP (36.77 AU vs 20.00 AU, CI95% 7.79-22.09, p ˂ 0.001). The probability of a CFP was associated to negative ANA, low ANA titer, and multiple positive MSA/MAA (p Ë‚ 0.001). In this study, we confirmed that CFP results using LIA are frequent, and are associated with low signal intensity MSA/MAA, negative ANA, lower titer ANA, and with multiple positive samples.

Ameliorated Renal Pathological Feature in MRL/MpJ-Faslpr/lpr Background Interleukin-36 Receptor-Deficient Mice.

Systemic autoimmune diseases frequently induce lupus nephritis, causing altered balance and expression of interleukin 36 receptor (IL-36R) ligands, including agonists (IL-36α, ß, γ) and antagonists (IL-36Ra, IL-38), in kidneys. Here, we established and analyzed a mouse model of lupus nephritis, MRL/MpJ-Faslpr/lpr with IL-36R-knockout (KO), compared to wild-type (WT) mice. In both genotypes, indices for immune abnormalities and renal functions were comparable, although female WT mice showed higher serum autoantibody levels than males. IL-36R ligand expression did not differ significantly between genotypes at the mRNA level or in IL-36α and IL-38 scores. However, glomerular lesions, especially mesangial matrix expansion, were significantly ameliorated in both sexes of IL-36R-KO mice compared to WT mice. Cell infiltration into the tubulointerstitium with the development of tertiary lymphoid structures was comparable between genotypes. However, the positive correlation with the IL-36α score in WT mice was not evident in IL-36R-KO mice. Fibrosis was less in female IL-36R-KO mice than in WT mice. Importantly, some IL-36α+ nuclei co-localized with acetylated lysine and GCN5 histone acetyltransferase, in both genotypes. Therefore, IL-36R ligands, especially IL-36α, contribute to the progression of renal pathology in lupus nephritis via IL-36R-dependent and IL-36R-independent pathways.

The occurrence timeline of steroid-induced ocular hypertension and cataract in children with systemic autoimmune diseases.

PURPOSE: Steroid-induced ocular hypertension (SIOH) and cataract can result in visual loss. This study evaluated the timetable of SIOH and steroid-induced posterior subcapsular cataract (SI-PSC) occurrences in children with systemic autoimmune diseases (SAD) undergoing long-term systemic corticosteroid treatment. METHODS: Thirty-seven children with SAD treated with long-term oral corticosteroids were enrolled in this study. Intraocular pressure (IOP), SI-PSC occurrences, visual field and peripapillary retinal nerve fibre layer (pRNFL) thicknesses were recorded every 3 months for at least 6 months. RESULTS: Of the 37 children, with average age 11.0 ± 2.9 years, 22 patients (59.5%) had SIOH, 2 progressed as glaucoma at the 18-month and 3-year follow-up, respectively, and 12 (32.4%) patients had SI-PSC. Among patients with SIOH, 45.5% (10/22) of them had SI-PSC occurrence, and among patients with normal IOP, 13.3% (2/15) of them had SI-PSC. Seventeen patients participated in a longitudinal study with a follow-up period of at least 18 months. The incidence of SIOH started at 1 month 52.9% (9/17) and gradually increased to 70.6% (12/17) at 6 months, then decreased to 35.3% (6/17). SI-PSC onset started at 6 months (17.6%, 3/17), and its occurrence increased to 35.3% (6/17) at 12 months and reached to 41.2% (7/17) at 18 months. The pRNFL was thicker in the children with SIOH than the healthy controls (p = 0.01). CONCLUSION: SIOH and SI-PSC are common coexistent complications in children with long-term corticosteroids treatment, and the occurrence time is during the first month and 6 months, respectively. Patients with SIOH have a higher probability of cataract.

Compartmentalization of interleukin 36 subfamily according to inducible and constitutive expression in the kidneys of a murine autoimmune nephritis model.

The interleukin (IL) 36 subfamily belongs to the IL-1 family and is comprised of agonists (IL-36α, IL-36ß, IL-36γ) and antagonists (IL-36Ra, IL-38). We previously reported IL-36α overexpression in renal tubules of chronic nephritis mice. To understand the localization status and biological relationships among each member of the IL-36 subfamily in the kidneys, MRL/MpJ-Faslpr/lpr mice were investigated as autoimmune nephritis models using pathology-based techniques. MRL/MpJ-Faslpr/lpr mice exhibited disease onset from 3 months and severe nephritis at 6-7 months (early and late stages, respectively). Briefly, IL-36γ and IL-36Ra were constitutively expressed in murine kidneys, while the expression of IL-36α, IL-36ß, IL-36Ra, and IL-38 was induced in MRL/MpJ-Faslpr/lpr mice. IL-36α expression was significantly increased and localized to injured tubular epithelial cells (TECs). CD44+-activated parietal epithelial cells (PECs) also exhibited higher IL-36α-positive rates, particularly in males. IL-36ß and IL-38 are expressed in interstitial plasma cells. Quantitative indices for IL-36α and IL-38 positively correlated with nephritis severity. Similar to IL-36α, IL-36Ra localized to TECs and PECs at the late stage; however, MRL/MpJ-Faslpr/lpr and healthy MRL/MpJ mice possessed IL-36Ra+ smooth muscle cells in kidney arterial tunica media at both stages. IL-36γ was constitutively expressed in renal sympathetic axons regardless of strain and stage. IL-36 receptor gene was ubiquitously expressed in the kidneys and was induced proportional to disease severity. MRL/MpJ-Faslpr/lpr mice kidneys possessed significantly upregulated IL-36 downstream candidates, including NF-κB- or MAPK-pathway organizing molecules. Thus, the IL-36 subfamily contributes to homeostasis and inflammation in the kidneys, and especially, an IL-36α-dominant imbalance could strongly impact nephritis deterioration.

Rare immunofluorescence patterns of autoantibodies on HEp-2 cells defined by ICAP identify different autoimmune diseases in the absence of associated specificities: a Spanish multicentre study.

OBJECTIVES: ANA are the most extensively used test for the diagnosis of systemic autoimmune diseases. However, testing by indirect immunofluorescence assays (IIFAs) on HEp-2 cells, the gold standard test, is time-consuming and needs expertise. Thus there is a trend to replace it with other automated solid-phase assays directed against specific ANA. Nonetheless, the Hep-2 cell is an autoantigen array and ANA have been classified into 29 types, some of them with no clear association with a specificity to be detected. It is especially in these uncommon patterns where no clinical relationship is found and no antigenic specificity is detected. Here we retrospectively collected clinical data from patients with confirmed uncommon HEp-2 IIFA patterns to search for an associated clinical condition. METHODS: We conducted an observational retrospective study including 608 patients with organ-specific and non-organ-specific autoimmune diseases (OSADs and NOSADs, respectively) with a confirmed rare pattern of ANA detected by IIFA on HEp-2 cells in the routine practice of the Spanish European Autoantibodies Standardization Initiative laboratories. Inclusion criteria are the existence of a minimum follow-up of 2 years and the availability of clinical data. RESULTS: Nuclear patterns were more frequent in SLE (P = 0.001) and SS (P = 0.001), whereas the cytoplasmic ones were significantly higher in SSc (P = 0.022) and inflammatory myositis (P = 0.016). Mitotic patterns did not show any preferences for a specific disease and 62.7% of them corresponded to the nuclear mitotic apparatus pattern (AC-26). The most frequent NOSADs in patients with the AC-26 pattern were SLE (28.6%), SS (11.9%) and RA (11.9%). The cytoplasmic HEp-2 IIFA patterns were equally distributed in both groups of patients. In the OSAD patients there was no predominant pattern, except for AC-6 in primary biliary cholangitis due to Sp-100 antibodies (P < 0.001). CONCLUSION: Detection of infrequent ANA might be a unique finding with no disease-associated specificities and could lead to the suspicion of an autoimmune disease.

Burden of illness among subgroups of patients with primary Sjögren's syndrome and systemic involvement.

OBJECTIVES: To describe how patients with primary SS (pSS) and systemic organ involvement are classified and clustered in routine practice. METHODS: This multinational, cross-sectional survey of real-world quantitative data was conducted across Europe and the US. Rheumatologists who treated seven or more adult patients per month with pSS and current/past systemic manifestations undertook a survey before completing a patient record form capturing demographic, clinical and treatment information for their next six eligible patients. Patients with a completed patient record form were invited to complete a patient self-completion questionnaire capturing insights into their disease and treatment. Subgroups were defined by physicians' assessment of disease severity; clusters were derived based on key clinical characteristics using latent class analysis. RESULTS: Rheumatologists completed 316 physician surveys and 1879 patient record forms; 888 patients completed the patient self-completion questionnaire. pSS severity reflected organ involvement and symptomatology. Latent class analysis produced five clusters distinguished by the organ systems involved and the presence of pain and fatigue symptoms at the time of the survey. A minority of patients [n = 67 (4%)] were categorized with multiple organ involvement and the highest frequency of pain and fatigue. A total of 324 patients (17%) were categorized as 'low burden'. The remaining three clusters exhibited high frequencies of articular involvement but were distinguished by the extent of other organ system involvement. CONCLUSION: Cluster analysis using a real-world cohort of patients with pSS and systemic organ involvement highlights the heterogeneous presentation of patients with pSS and confirms the importance of pain and fatigue as well as organ involvement when determining disease burden.

A systematic review of the incidence, risk factors and prognosis of acute exacerbation of systemic autoimmune disease-associated interstitial lung disease.

INTRODUCTION: Acute exacerbation (AE) is a devastating phenomenon and reported to be complicated with systemic autoimmune disease-associated interstitial lung disease (ILD). The aim of this study was to investigate the incidence and prognosis of AE of systemic autoimmune disease-ILD and clarify relevant clinical information predictive of these outcomes. METHOD: This study was designed as a systematic review and meta-analysis. A primary study except for a case report, which reported the incidence and/or prognosis of AE of systemic autoimmune disease-ILD, was eligible for the review. Electronic databases such as Medline and EMBASE were searched from 2002 through 23 February 2020. Two reviewers independently selected eligible reports and extracted relevant data. Risk of bias of individual studies was assessed similarly. The incidence and prognosis of the disease were analysed qualitatively. Univariate results of risk and prognostic factors were combined if feasible. RESULTS: Out of a total of 2662 records, 24 studies were eligible. A total of 420 subjects with 45.7% of men developed AE of systemic autoimmune disease-ILD and the two major underlying systemic autoimmune diseases were rheumatoid arthritis (34.2%) and polymyositis/dermatomyositis (31.9%). The frequency ranged from 4.3 to 32.9% with the incident rate being 3.19 and 5.77 per 100 patient-years and all-cause mortality was between 30.0 and 58.3% at 90 days. Age at initial presentation was significantly associated with the development of AE of systemic autoimmune disease-ILD with an HR of 1.22 (95%CI 1.05-1.50) while a percentage of predicted diffusing capacity of the lung for carbon monoxide (%DLCO) was also significantly associated with the development of the disease with an HR of 0.95 (95%CI 0.90-1.00) and an OR of 0.97 (95%CI 0.95-0.99). Partial pressure of arterial oxygen/fraction of inspired oxygen ratio (PaO2/FiO2) at AE was significantly associated with all-cause mortality of AE of systemic autoimmune disease-ILD with an HR of 0.99 (95%CI 0.98-0.99). CONCLUSION: AE of systemic autoimmune disease-ILD was not uncommon and demonstrated dismal prognosis. Age at initial presentation and %DLCO were deemed as risk factors while PaO2/FiO2 at AE was considered as a prognostic factor of the disease. Registration CRD42019138941.

BXSB/MpJ-Yaa mouse model of systemic autoimmune disease shows increased apoptotic germ cells in stage XII of the seminiferous epithelial cycle.

In mammals, the reproductive system and autoimmunity regulate mutual functions. Importantly, systemic autoimmune diseases are thought to cause male infertility but the underlying pathological mechanism remains unclear. In this study, the morpho-function of the testes in BXSB/MpJ-Yaa mice was analyzed as a representative mouse model for systemic autoimmune diseases to investigate the effect of excessive autoimmunity on spermatogenesis. At 12 and 24 weeks of age, BXSB/MpJ-Yaa mice showed splenomegaly and increased levels of serum autoantibodies, whereas no controls showed a similar autoimmune condition. In histological analysis, the enlarged lumen of the seminiferous tubules accompanied with scarce spermatozoa in the epididymal ducts were observed in some of the BXSB/MpJ-Yaa and BXSB/MpJ mice but not in C57BL/6N mice. Histoplanimetrical analysis revealed significantly increased residual bodies and apoptotic germ cells in the seminiferous tubules in BXSB/MpJ-Yaa testes without apparent inflammation. Notably, in stage XII of the seminiferous epithelial cycles, the apoptotic germ cell number was remarkably increased, showing a significant correlation with the indices of systemic autoimmune disease in BXSB/MpJ-Yaa mice. Furthermore, the Sertoli cell number was reduced at the early disease stage, which likely caused subsequent morphological changes in BXSB/MpJ-Yaa testes. Thus, our histological study revealed the altered morphologies of BXSB/MpJ-Yaa testes, which were not observed in controls and statistical analysis suggested the effects of an autoimmune condition on this phenotype, particularly the apoptosis of meiotic germ cells. BXSB/MpJ-Yaa mice were shown to be an efficient model to study the relationship between systemic autoimmune disease and the local reproductive system.

Genetic differences between type 1 diabetes with and without other autoimmune diseases.

BACKGROUND: Clusters of autoimmune diseases (ADs) are present in some people with type 1 diabetes. This clustering suggests the existence of common genetic backgrounds for abnormal autoimmunity in these individuals. However, the genetic differences between type 1 diabetes patients with and without other ADs are not well known. METHODS: To investigate the clinical background and genetic differences between type 1 diabetes patients with and without other ADs, single nucleotide polymorphisms (SNPs) in the CTLA4, SUMO4, PTPN22, IRF5, STAT4, and BLK genes were analysed by using either a TaqMan assay or direct sequencing. The frequencies of alleles, genotypes of each gene, and the human leukocyte antigen (HLA) haplotype were analysed to investigate differences among 3 groups: type 1 diabetes with systemic ADs (group A), type 1 diabetes with other organ-specific ADs (group B), and type 1 diabetes without other ADs (group C). RESULTS: The frequency of the C allele in the -1123G > C SNP in the PTPN22 gene promoter was significantly higher in groups A and B than in group C (P = .0258 and .0207, respectively). The allele frequencies of the other SNPs were comparable. The frequency of HLA DRB1*0405-DQB1*0401 was significantly higher in groups A and B than in group C (P = .021 and .0395, respectively). CONCLUSIONS: The -1123G > C SNP in the PTPN22 gene promoter and HLA DRB1*0405-DQB1*0401 might influence the concurrence of systemic and organ-specific ADs in patients with type 1 diabetes.

Evaluation of a New Multiparametric Microdot Array-Based Immunoassay Panel for Systemic Autoimmune Disease Diagnosis.

BACKGROUND: The early reliable detection and quantification of autoantibodies play an important role in autoimmune disease diagnosis and in disease-course monitoring. New technologies, such as the multiplexed determination of autoantibodies, have recently been introduced and are being adopted more frequently. The aim of this study was to evaluate the ability of a new microdot array-based multiparametric assay (ZENIT AMiDot CTD panel, A. Menarini Diagnostics, Firenze, Italy) to correctly classify patients with autoimmune rheumatic diseases (ARDs) and compare it to a fluorescence enzyme immunoassay (FEIA) for the detection of anti-ENAs. METHODS: The study included 69 consecutive samples from patients with ARDs that were analyzed using two different methods (FEIA and AMiDot) to detect anti-CENP B and six anti-ENA antibodies: anti-Scl-70, anti-SSB/La, anti-Jo-1, anti-U1-RNP, anti-Ro52, and anti-Ro60. The control group sera came from sixty-eight blood donors. Tests were run on the automated slide processor ZENIT FLOW, and then the slides were imaged and analyzed using ZENIT fast. RESULTS: Since the samples were selected for at least one antibody positivity with an ARD diagnosis, we did not calculate clinical sensitivity but only specificity, which was 98.53%, ranging from 90% for anti-SSB/La antibodies to 100% for anti-CENP B ones. Mean agreement among the methods assessed by Cohen's kappa was 0.816 ± 0.240. CONCLUSIONS: The assay demonstrated good clinical performance and may be considered a valuable aid in detecting ARD patients, offering an alternative to methods such as FEIA which are largely in use today.

Long-Term Outcome of Tofacitinib Treatment for Systemic Autoimmune Disease-Associated Refractory Scleritis.

PURPOSE: To report the long-term outcome of three refractory anterior scleritis cases successfully treated with tofacitinib, a Janus-associated kinase inhibitor. METHODS: Three patients with systemic autoimmune disease-associated anterior scleritis (two with rheumatoid arthritis and one with systemic lupus erythematosus), resistant to conventional immunomodulatory therapy, were subsequently treated with tofacitinib (10 mg/day). RESULTS: Tofacitinib resulted in complete resolution of scleritis in all patients. During the 39-78 months of follow-up, no recurrence of scleritis occurred, and no adverse effects associated with tofacitinib were noted. At the last follow-up, all patients were free of scleritis with two patients receiving tofacitinib monotherapy and one without. CONCLUSION: Tofacitinib can be a safe and effective treatment for noninfectious refractory scleritis, warranting further investigation in large clinical trials.

Occurrence of Bullous Pemphigoid in a Longstanding Case of Rheumatoid Arthritis in an Indian Patient: A Rare Association.

Bullous pemphigoid is a subepidermal blistering disease that rarely involves the mucous membranes and possesses circulating antibodies against BP antigen II (BP180) and BP antigen I (BP230). Rheumatoid arthritis (RA) is a progressive inflammatory autoimmune disease that is characterized by joint inflammation and systemic involvement. The co-occurrence of RA, which is likewise linked to autoimmunity, with bullous pemphigoid may not be merely coincidental. A 55-year-old female, a known case of RA for 25 years, presented to us with multiple pruritic vesiculobullous lesions. After a thorough clinical and laboratory assessment, she was diagnosed with bullous pemphigoid. This emphasizes the significance of the simultaneous occurrence of autoimmune disorders and the need for vigilant and timely identification.

Functional significance of DNA methylation: epigenetic insights into Sjögren's syndrome.

Sjögren's syndrome (SjS) is a systemic, highly diverse, and chronic autoimmune disease with a significant global prevalence. It is a complex condition that requires careful management and monitoring. Recent research indicates that epigenetic mechanisms contribute to the pathophysiology of SjS by modulating gene expression and genome stability. DNA methylation, a form of epigenetic modification, is the fundamental mechanism that modifies the expression of various genes by modifying the transcriptional availability of regulatory regions within the genome. In general, adding a methyl group to DNA is linked with the inhibition of genes because it changes the chromatin structure. DNA methylation changes the fate of multiple immune cells, such as it leads to the transition of naïve lymphocytes to effector lymphocytes. A lack of central epigenetic enzymes frequently results in abnormal immune activation. Alterations in epigenetic modifications within immune cells or salivary gland epithelial cells are frequently detected during the pathogenesis of SjS, representing a robust association with autoimmune responses. The analysis of genome methylation is a beneficial tool for establishing connections between epigenetic changes within different cell types and their association with SjS. In various studies related to SjS, most differentially methylated regions are in the human leukocyte antigen (HLA) locus. Notably, the demethylation of various sites in the genome is often observed in SjS patients. The most strongly linked differentially methylated regions in SjS patients are found within genes regulated by type I interferon. This demethylation process is partly related to B-cell infiltration and disease progression. In addition, DNA demethylation of the runt-related transcription factor (RUNX1) gene, lymphotoxin-α (LTA), and myxovirus resistance protein A (MxA) is associated with SjS. It may assist the early diagnosis of SjS by serving as a potential biomarker. Therefore, this review offers a detailed insight into the function of DNA methylation in SjS and helps researchers to identify potential biomarkers in diagnosis, prognosis, and therapeutic targets.

Therapeutic Outcomes of Non-Infectious Scleritis Treated with Tumor Necrosis Factor-Alpha Inhibitors.

PURPOSE: We determine the efficacy of tumor necrosis factor-α (TNF) inhibitors in establishing scleritis quiescence. METHODS: We conducted a multicenter retrospective chart review of patients with non-infectious scleritis treated with a TNF inhibitor for at least 6 months. The primary endpoint was scleritis quiescence at 6 months. Secondary endpoints included scleritis quiescence at 12 months, TNF inhibitor effects on concurrent doses of systemic corticosteroids and visual acuity outcomes at 6 and 12 months. RESULTS: At 6 months, 82.2% (37/45) of subjects obtained scleritis quiescence with TNF inhibition. At 12 months, 76.2% (32/42) of subjects remained quiescent. Baseline daily corticosteroid use (21.5 ± 21.6 mg) decreased to 5.4 ± 8.3 mg by 6 months (p < 0.0001) and 2.8 ± 6.1 mg by 12 months (p < 0.001). There was no significant difference between the baseline and 6-month BCVA (p = 0.52). CONCLUSIONS: TNF inhibitors are an effective scleritis therapy with significant systemic corticosteroid sparing effect.

Newly Diagnosed Sjogren Syndrome in an Elderly Patient on Dialysis: A Case Report.

Sjogren syndrome (SS) is a chronic, systemic autoimmune disease that primarily affects the exocrine glands, causing dry eyes and mouth, but also presents with a variety of other symptoms. SS is a common connective tissue disease but it can be difficult to diagnose due to the non-specific symptoms and lack of diagnostic markers in many cases. This report describes a case of an elderly patient on dialysis with newly diagnosed SS. The patient had been unable to eat a normal diet for a year, but treatment had not been initiated, presumably because of his age and the fact that he was on dialysis. The patient's symptoms improved with the administration of glucocorticoids. This is a very educational case for physicians to recognize undiagnosed SS patients presenting with non-specific symptoms.

Subglottic Mass as Isolated Manifestation of Relapsing Polychondritis at Presentation.

Relapsing polychondritis (RP) is a rare systemic disease that is characterized by recurrent episodic inflammation of the cartilaginous structures of the body, resulting in their progressive destruction and subsequent replacement with fibrotic scar. We present a case of RP that initially manifested with subglottic involvement and we propose an innovative strategy for the treatment for laryngeal RP in phase of active inflammation. A multidisciplinary approach (rheumatologist, otolaryngologist, immunologist, internist, cardiologist, etc) and adequate follow-up are essential. The timeliness of the diagnosis is fundamental to contain the destructive effects on the cartilages involved.

Long-Term Benefit of Perlingual Polybacterial Vaccines in Patients with Systemic Autoimmune Diseases and Active Immunosuppression.

INTRODUCTION: We have previously shown that trained-immunity-based vaccines, namely TIbV, significantly reduce the rate of recurrent infections, both of the respiratory tract (RRTI) and urinary tract infections (RUTI) in SAD patients on disease-modifying drugs (DMARDs). OBJECTIVE: We evaluated the frequency of RRTI and RUTI from 2018 to 2021 in those SAD patients that received TIbV until 2018. Secondarily, we evaluated the incidence and clinical course of COVID-19 in this cohort. METHODS: A retrospective observational study was conducted in a cohort of SAD patients under active immunosuppression immunized with TIbV (MV130 for RRTI and MV140 for RUTI, respectively). RESULTS: Forty-one SAD patients on active immunosuppression that were given TIbV up to 2018 were studied for RRTI and RUTI during the 2018-2021 period. Approximately half of the patients had no infections during 2018-2021 (51.2% no RUTI and 43.5% no RRTI at all). When we compared the 3-year period with the 1-year pre-TIbV, RRTI (1.61 ± 2.26 vs. 2.76 ± 2.57; p = 0.002) and RUTI (1.56 ± 2.12 vs. 2.69 ± 3.07; p = 0.010) episodes were still significantly lower. Six SAD patients (four RA; one SLE; one MCTD) with RNA-based vaccines were infected with SARS-CoV-2, with mild disease. CONCLUSIONS: Even though the beneficial protective effects against infections of TIbV progressively decreased, they remained low for up to 3 years, with significantly reduced infections compared to the year prior to vaccination, further supporting a long-term benefit of TIbV in this setting. Moreover, an absence of infections was observed in almost half of patients.

Risk of systemic autoimmune diseases with antiarrhythmic drugs in arrhythmia patients: A retrospective cohort study.

AIM: The risk factors for systemic autoimmune disease (SAD)s with antiarrhythmic drug(AAD)s in arrhythmia patients are still unclear. This study was discussed this risk factors for SADs with AADs in arrhythmia patients. METHODS: This study was a retrospective cohort design and analyzed this relationship in an Asian population. Patients without a prior diagnosis of SADs were identified from Taiwan's National Health Insurance Research Database from January 1, 2000 to December 31, 2013. Cox regression models were estimated the hazard ratio (HR) with 95% confidence interval [CI] of SAD. RESULTS: We estimated the data of participants aged ≧ 20 or ≦ 100 years old and free of SADs at baseline. AAD users (n = 138376) had a significantly increased risk of SADs over non-AAD users. There was a significant higher risk of developing SADs in all age and sex categories. The patients who received AADs, the autoimmune disease with the significantly higher risk was systemic lupus erythematous (SLE) (adjusted HR [aHR] 1.53, 95%CI, 1.04-2.26), Sjögren syndrome (SjS) (adjusted HR [aHR] 2.06, 95%CI, 1.59-2.66) and rheumatoid arthritis (RA) (aHR, 1.57, 95%CI, 1.26-1.94). CONCLUSION: We concluded that there were statistical associations between AADs and SADs, and the higher incidence was SLE, SjS and RA in arrhythmia patients.

Relapsing Polychondritis in a Patient With Rheumatoid Arthritis: Improved With Pentoxifylline.

Relapsing polychondritis (RP) is a rare autoimmune condition that involves the recurrent inflammation of cartilage throughout the body, with a predilection for auricular and nasal cartilage. Given its rarity and diverse clinical presentations, RP is frequently misdiagnosed or left untreated, which can lead to significant morbidity and mortality. When it is correctly diagnosed, there are no standardized guidelines on the treatment of RP to date. Management of this disease requires a multidisciplinary approach, and about 30% of patients with RP have other autoimmune disorders, further complicating the approach to targeted treatment. Biologic agents (including TNF inhibitors) are commonly used. We present a compelling case of a 46-year-old female with rheumatoid arthritis (well-controlled on adalimumab) and hypothyroidism who presented to the dermatology clinic with recurrent episodes of painful, swollen, and erythematous ears, leading to a clinical diagnosis of relapsing polychondritis. Off-label use of oral pentoxifylline, along with topical corticosteroids, led to significant improvement in her symptoms. Dermatologists play an important role in the diagnosis of this rare disorder, as skin manifestations may be the initial presenting sign of RP. Further research into potentially effective treatments is needed. Timely identification and management of RP may prevent the progression of cartilage destruction, thus improving patients' long-term prognosis and overall quality of life.

Maternal, neonatal, pregnancy outcome characteristics of pregnant women with high plasma cell-free DNA concentration in non-invasive prenatal screening: a retrospective analysis.

Objective: Cell-free DNA (cfDNA) is a useful biomarker in various clinical contexts. Herein, we aimed to identify maternal characteristics and pregnancy outcomes associated with a failed NIPS test due to high cfDNA concentrations. Methods: A retrospective study of cases with high plasma cfDNA concentration in pregnant women in which NIPS test was performed (from 174,318 cases). We reported the detection of 126 cases (118 with complete clinical information) in which the high amount of cfDNA did not allow the performance of NIPS and study the possible causes of this result. Results: 622 (0.35%) of 174,318 pregnant women had failed the NIPS test, including 126 (20.3%) cases with high plasma cfDNA concentrations. The failed NIPS due to high plasma cfDNA concentrations was associated with maternal diseases and treatment with low-molecular-weight heparin (LMWH). Further follow-up of the 118 pregnant women in the case group revealed that the pregnancy outcomes included 31 premature deliveries, 21 abortions. The cfDNA concentrations of pregnant women with preterm deliveries were 1.15 (0.89, 1.84), which differed significantly from those who had full-term deliveries. Conclusions: Among pregnant women with high cfDNA concentrations, systemic autoimmune diseases, pregnancy complications and LMWH were associated with increased incidence of failed NIPS test. High maternal cfDNA concentrations may not be associated with chromosomal abnormalities in the fetus. However, they should be alerted to the possibility of preterm births and stillbirths. Further clinical studies on pregnant women with high cfDNA concentrations are required.