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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Progressive pulmonary fibrosis in systemic autoimmune diseases. A real life study.

INTRODUCTION: Interstitial lung diseases associated with systemic autoimmune diseases (ILD-SAD) can progress to a fibrotic form that can benefit from antifibrotic treatment. The aim of the study is to describe a cohort of patients with ILD-SAD who manifest progressive pulmonary fibrosis treated with antifibrotics. METHODS: Single-centre retrospective observational study from a tertiary care hospital on a cohort of patients with ILD-SAD with progressive pulmonary fibrosis evaluated in a joint pulmonology and rheumatology clinic that initiated treatment with antifibrotic drugs between 01/01/2019 and 01/12/2021. Clinical characteristics were analysed. The evolution of pulmonary function test and adverse effects during treatment were described. RESULTS: 18 patients were included. The mean age was 66.7 ±â€¯12.7 years, with a higher frequency of females (66.7%). Systemic sclerosis (SS) was the most frequent systemic autoimmune disease (36.8%). The majority of patients were receiving systemic glucocorticoid treatment (88.9%), 72.2% of patients were receiving treatment with disease-modifying drugs, the most frequent being mycophenolate mofetil (38.9%), and 22.2% with rituximab. Functional stability was observed after the start of antifibrotic treatment. Two patients died during follow-up, one due to progression of ILD. CONCLUSION: Our study suggests a beneficial effect of antifibrotic treatment added to immunomodulatory treatment in patients with fibrotic ILD-SAD in real life. In our cohort, patients with ILD-SAD with progressive fibrosing involvement show functional stability after starting antifibrotic treatment. Treatment tolerance was relatively good with a side effect profile similar to that described in the medical literature.

Fibrosis pulmonar en enfermedades autoinmunes sistémicas. Un estudio en vida real / Progressive pulmonary fibrosis in systemic autoimmune diseases. A real life study

Introducción: Las enfermedades pulmonares intersticiales difusas asociadas a enfermedades autoinmunes sistémicas (EPID-EAS) pueden presentar una progresión fibrótica. El objetivo principal del estudio es describir una serie de casos de pacientes con EPID-EAS que cursan con fibrosis pulmonar progresiva e inician tratamiento con fármacos antifibróticos. Métodos: Estudio observacional retrospectivo unicéntrico de un hospital de tercer nivel sobre una serie de casos de pacientes con EPID-EAS con fibrosis pulmonar progresiva valorados en una consulta conjunta de neumología y reumatología, que iniciaron tratamiento con fármacos antifibróticos entre el 01/01/2019 y el 01/12/2021. Se analizaron las características epidemiológicas, clínicas, funcionales, radiológicas y terapéuticas al inicio del tratamiento, y la evolución funcional durante el tratamiento, así como los efectos adversos. Resultados: Se incluyeron 18 pacientes. La edad media observada fue de 66,7±12,7 años, con mayor frecuencia de sexo femenino (66,7%), siendo la esclerosis sistémica la enfermedad autoinmune sistémica más frecuente (36,8%). La mayoría de los pacientes se encontraban en tratamiento con glucocorticoides sistémicos (88,9%), un 72,2% de pacientes con fármacos modificadores de la enfermedad, siendo el más frecuente el micofenolato mofetilo (38,9%), y un 22,2% con rituximab. Se observó una estabilidad funcional tras el inicio del tratamiento antifibrótico. Fallecieron 2 pacientes durante el seguimiento, uno de ellos como consecuencia de la progresión de la enfermedad intersticial pulmonar. Conclusión: Nuestro estudio sugiere un efecto beneficioso del tratamiento antifibrótico añadido al tratamiento inmunomodulador en pacientes con EPID-EAS fibrótica en vida real. En nuestra serie de casos, los pacientes con EPID-EAS con afectación fibrosante progresiva muestran una estabilidad funcional tras el inicio del tratamiento antifibrótico...(AU)

Introduction: Interstitial lung diseases associated with systemic autoimmune diseases (ILD-SAD) can progress to a fibrotic form that can benefit from antifibrotic treatment. The aim of the study is to describe a cohort of patients with ILD-SAD who manifest progressive pulmonary fibrosis treated with antifibrotics. Methods: Single-centre retrospective observational study from a tertiary care hospital on a cohort of patients with ILD-SAD with progressive pulmonary fibrosis evaluated in a joint pulmonology and rheumatology clinic that initiated treatment with antifibrotic drugs between 01/01/2019 and 01/12/2021. Clinical characteristics were analysed. The evolution of pulmonary function test and adverse effects during treatment were described. Results: 18 patients were included. The mean age was 66.7±12.7 years, with a higher frequency of females (66.7%). Systemic sclerosis (SS) was the most frequent systemic autoimmune disease (36.8%). The majority of patients were receiving systemic glucocorticoid treatment (88.9%), 72.2% of patients were receiving treatment with disease-modifying drugs, the most frequent being mycophenolate mofetil (38.9%), and 22.2% with rituximab. Functional stability was observed after the start of antifibrotic treatment. Two patients died during follow-up, one due to progression of ILD. Conclusion: Our study suggests a beneficial effect of antifibrotic treatment added to immunomodulatory treatment in patients with fibrotic ILD-SAD in real life. In our cohort, patients with ILD-SAD with progressive fibrosing involvement show functional stability after starting antifibrotic treatment. Treatment tolerance was relatively good with a side effect profile similar to that described in the medical literature.(AU)

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.

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.

Impact of Systemic Autoimmune Diseases on Treatment Outcomes and Radiation Toxicities in Patients with Stage I Non-Small Cell Lung Cancer Receiving Stereotactic Body Radiation Therapy: A Matched Case-Control Analysis.

We aimed to evaluate the impact of systemic autoimmune diseases (SADs) on treatment outcomes and radiation toxicities following stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC). We queried an institution-based database on patients with SADs treated with SBRT for lung cancer between 2001 and 2016 (SAD group). Each patient was matched to three controls without SADs. The primary outcomes of interest were the overall survival (OS) and local control rate (LCR). The secondary outcomes were radiation toxicities of grades ≥2 (≥G2). Twelve patients with SADs were matched to 36 controls. The median follow-up duration was 3.6 years. There was a significant intergroup difference in the OS (hazard ratio [HR]: 4.11, 95% confidence incidence [CI]: 1.82−9.27, p < 0.001) and LCR (HR: 15.97, 95% CI: 2.89−88.29, p < 0.001). However, there were no significant intergroup differences in the odds of acute (odds ratio [OR]: 0.38, 95% CI: 0.02−8.91, p = 0.550) and late (OR: 2.20, 95% CI: 0.32−15.10, p = 0.422) ≥G2 radiation pneumonitis. No other ≥G2 toxicities were identified. In conclusion, although radiation toxicities are not enhanced by SADs, SADs are risk factors of poor prognosis following SBRT for stage I NSCLC.

The role of the intestinal microbiome in antiphospholipid syndrome.

The antiphospholipid syndrome (APS) is a thrombotic autoimmune disease in which the origin of the disease-characterizing autoantibodies is unknown. Increased research effort into the role of the intestinal microbiome in autoimmunity has produced new insights in this field. This scoping review focusses on the gut microbiome in its relation to APS. EMBASE and MEDLINE were searched for original studies with relevance to the relation between the gut microbiome and APS. Thirty studies were included. Work on systemic lupus erythematosus, which strongly overlaps with APS, has shown that patients often display an altered gut microbiome composition, that the disease is transferable with the microbiome, and that microbiome manipulation affects disease activity in murine lupus models. The latter has also been shown for APS, although data on microbiome composition is less consistent. APS patients do display an altered intestinal IgA response. Evidence has accrued for molecular mimicry as an explanatory mechanism for these observations in APS and other autoimmune diseases. Specific gut microbes express proteins with homology to immunodominant APS autoantigens. The disease phenotype appears to be dependent on these mimicking proteins in an APS mouse model, and human APS B- and T-cells indeed cross-react with these mimics. Pre-clinical evidence furthermore suggests that diet may influence autoimmunity through the microbiome, as may microbial short chain fatty acid production, though this has not been studied in APS. Lastly, the microbiome has been shown to affect key drivers of thrombosis, and may thus affect APS severity through non-immunological mechanisms. Overall, these observations demonstrate the impact of the intestinal microbiome on autoimmunity and the importance of understanding its role in APS.

Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial.

BACKGROUND: Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares. The Synbiose 1 study primarily focused on immunological effects and shows the preliminary clinical benefit of combined rituximab and belimumab in SLE. The Synbiose 2 study will evaluate the clinical efficacy of combining belimumab with rituximab in patients with severe SLE, allowing the tapering of prednisolone and mycophenolate. METHODS: Synbiose 2 is a phase 3, multicenter, randomized, controlled, open-label 2-year clinical trial. Seventy adults with severe SLE including lupus nephritis will be randomized 1:1 to receive either standard of care consisting of prednisolone and mycophenolate as induction and maintenance treatment, or belimumab and rituximab combined with standard of care as induction treatment, followed by prednisolone and belimumab as maintenance treatment. The primary objective is to assess whether combined B cell therapy will lead to a reduction of treatment failure. Secondary endpoints are complete and partial clinical and renal response and the improvement of SLE-specific autoimmune phenomena. Safety endpoints include the incidence of adverse events, with a special interest in infections. DISCUSSION: The Synbiose 2 trial is the first multicenter phase 3 clinical trial investigating combined B cell targeted therapy in SLE, including lupus nephritis. The outcome of this study will provide further evidence for the clinical efficacy of this new treatment strategy in severe SLE. TRIAL REGISTRATION: ClinicalTrials.gov NCT03747159 . Registered on 20 November 2018.

Neuropilin-1 (NRP1) expression distinguishes self-reactive helper T cells in systemic autoimmune disease.

Pathogenic T helper cells (Th cells) that respond to self-antigen cannot be easily distinguished from beneficial Th cells. These cells can generate systemic autoimmune disease in response to widely expressed self-antigens. In this study, we have identified neuropilin-1 (NRP1) as a cell surface marker of self-reactive Th cells. NRP1+ Th cells, absent in non-regulatory T cell subsets in normal mice, appeared in models of systemic autoimmune disease and strongly correlated with disease symptoms. NRP1+ Th cells were greatly reduced in Nr4a2 cKO mice, which have reduced self-reactive responses but showed normal responses against exogenous antigens. Transfer of NRP1+ Th cells was sufficient to initiate or accelerate systemic autoimmune disease, and targeting NRP1-expressing Th cells therapeutically ameliorated SLE-like autoimmune symptoms in BXSB-Yaa mice. Peripheral NRP1+ Th cells were significantly increased in human SLE patients. Our data suggest that self-reactive Th cells can be phenotypically distinguished within the Th cell pool. These findings offer a novel approach to identify self-reactive Th cells and target them to treat systemic autoimmune disease.

POEMS Syndrome: A Case Report and Review of the Literature.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein elevation, and skin changes (POEMS) syndrome is a rare multisystem disorder that occurs due to an underlying plasma cell dyscrasia. A diagnosis is made with the presence of two mandatory criteria and at least one major and one minor criterion. We present a case of a 28-year-old patient who presented with weakness of bilateral arms and legs, thinning of hands, and swelling of bilateral lower limbs and abdomen. The patient also reported weight loss and loss of appetite. Examination revealed areflexic quadriparesis with sensory loss, diffuse lymphadenopathy, pleural effusion, ascites, and pulmonary hypertension. Investigations showed elevated erythrocyte sedimentation rate (ESR). Nerve conduction studies revealed severe axonal polyneuropathy of all nerves. Lymph node biopsy showed Castleman disease. A diagnosis of POEMS syndrome was made and he was sent for a stem cell transplant, which is the definitive treatment in patients eligible for stem cell transplant.